PYRROLO[2,3-d]PYRIMIDINE COMPOUNDS

Abstract: A compound of formula (I) wherein R<1>, R<2> and R<3> are as defined in the description, and are inhibitors of the enzyme protein tyrosine kinases such as Janus Kinase (3) and as such are useful therapy as immunosuppressive agents for organ transplants, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia and other autoimmune diseases.

Description: PYRROLO[2,3-d]PYRIMIDINE COMPOUNDS Background of the Invention The present invention relates to pyrrolo[2,3-d]pyrιmιdιne compounds which are inhibitors of protein tyrosine kinases, such as the enzyme Janus Kinase 3 (hereinafter also referred to as JAK3) and as such are useful therapy as immunosuppressive agents for organ transplants, lupus, multiple sclerosis, rheumatoid arthπtis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia and other indications where immunosuppression would be desirable This invention also relates to a method of using such compounds in the treatment of the above indications in mammals, especially humans, and the phamaceutical compositions useful therefor JAK3 is a member of the Janus family of protein tyrosine kinases Although the other members of this family are expressed by essentially all tissues, JAK3 expression is limited to hematopoetic cells This is consistent with its essential role in signaling through the receptors for IL-2, IL-4, IL-7, IL-9 and IL-15 by non-covalent association of JAK3 with the gamma chain common to these multichain receptors XSCID patient populations have been identified with severely reduced levels of JAK3 protein or with genetic defects to the common gamma chain, suggesting that immunosuppression should result from blocking signaling through the JAK3 pathway Animal studies have suggested that JAK3 not only plays a critical role in B and T lymphocyte maturation, but that JAK3 is constitutively required to maintain T cell function Modulation of immune activity through this novel mechanism can prove useful in the treatment of T cell proliferative disorders such as transplant rejection and autoimmune diseases Summary of the Invention The present invention relates to a compound of the formula or the pharmaceutically acceptable salt thereof, wherein R 1 is a group of the formula wherein y is 0, 1 or 2, R 4 ιs selected from the group consisting of hydrogen, (C C^alkyl, (C 2 -C 6 )alkenyl, (C 2 - C 6 )alkynyl wherein the alkyl, alkenyl and alkynyl groups are optionally substituted by deuterium, hydroxy, ammo, tnfluoromethyl, (C 1 -C 4 )alkoxy, (C 1 -C 6 )acyloxy, (C,-C 6 )alkylamιno, ((C 1 -C 6 )alkyl) 2 amιno, cyano, nitro, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl or (CrC^acylammo, or R 4 is (C 3 -C 10 )cycloalkyl wherein the cycloalkyl group is optionally substituted by deuterium, hydroxy, ammo, tnfluoromethyl, (C 1 -C 6 )acyloxy, (C r C 6 )acylamιno, (C 1 -C 6 )alkylamιno, ((C r C 6 )alkyl) 2 amιno, cyano, cyano(C 1 -C 6 )alkyl, tπfluoromethyl(C 1 -C 6 )alkyl, nitro, nιtro(C 1 -C 6 )alkyl or (C T -CgJacylammo, R 5 is selected from the group consisting of (C C 3 )alkyl(dιfluoromethylene)(C r C 3 )alkyl, (C 3 -C 10 )cycloalkyl wherein the cycloalkyl group is optionally substituted by one to five carboxy, cyano, am o, deuterium, hydroxy, (CrC alkyl, (C C 6 )alkoxy, halo, (C 1 -C 6 )acyl, (C 1 -C 6 )alkylamιno, amιno(C r C 6 )alkyl, (C 1 -C 6 )alkoxy-CO-NH, (C.|-C 6 )alkylamιno-CO-, (C 2 -C 6 )alkenyl, (C 2 -C 6 ) alkynyl, amιno(C 1 -C 6 )alkyl, hydroxy(C r C 6 )alkyl, (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C 1 -C 6 )acyloxy(C 1 -C 6 )alkyl, nitro, cyano(C r C 6 )alkyl, halo(C r C 6 )alkyl, nιtro(C r C 6 )alkyl, tnfluoromethyl, trifluoromethy CrCeJalkyl, (C r C 6 )acylamιno, (C 1 -C 6 )acylamιno(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy(C 1 -C 6 )acylamιno, amιno(C 1 - C 6 )acyl, amιno(C 1 -C 6 )acyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylamιno(C 1 -C 6 )acyl, ((C 1 -C 6 )alkyl) 2 amιno(C 1 - C 6 )acyl, R 15 R 16 N-C0-0-, R 15 R 16 N-C0-(C 1 -C 6 )alkyl, (C ^alkyl-SCO , R 15 R 6 NS(0) m , R 15 R 16 NS(0) m (C r C 6 )alkyl, R 15 S(0) m R 16 N, R 15 S(0) m R 16 N(C 1 -C 6 )alkyl wherein m is 0, 1 or 2 and R 15 and R 16 are each independently selected from hydrogen or (CrC^alkyl, or R 5 is (C 3 - C 10 )cycloalkyl(C 1 -C 6 )alkyl, (C l -C 6 )acyloxy(C 1 -C 6 )alkyl, (C 2 -C 6 )alkoxy(C 1 -C 6 )alkyl, pιperazιnyl(C r C 6 )alkyl, (C 1 -C 6 )acylamιno(C 1 -C 6 )alkyl, (C 6 -C 10 )aryl(C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C 5 -C 8 )heteroaryl(C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylthιo(C 1 -C 6 )alkyl, C 6 )alkyl, (C 1 -C 6 )alkylsulfιnyl(C 1 -C 6 )alkyl, (C r C 6 )alkylsulfonyl(C 1 -C 6 )alkyl, (C 6 -C 10 )arylsulfonyl(C,-C 6 )alkyl, amιno(C r C 6 )alkyl, (C C 6 )alkylamιno(C r C 6 )alkyl, ((C r C 6 )alkyl) 2 amιno, (C r C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl wherein the alkyl, alkenyl and alkynyl groups are optionally substituted by one to five cyano, nitro, halo, deuterium, hydroxy, carboxy, (C 1 -C 6 )acylamιno, (C 1 -C 6 )alkoxy(C 1 -C 6 )acylamιno, amιno(C 1 -C 6 )acyl, (C 1 -C 6 )alkylamιno(C 1 -C 6 )acyl or ((C 1 -C 6 )alkyl) 2 amιno(C 1 -C 6 )acyl, or R 5 is R 13 CO(C 1 -C 6 )alkyl or R 13 CO(C 3 -C 10 )cycloalkyl wherein R 13 is R 20 O or R 20 R 21 N wherein R 20 and R 21 are each independently selected from the group consisting of hydrogen, deuterium, (C - C 6 )alkyl, (C 6 -C 10 )aryl(C 1 -C 6 )alkyl or (Cg-CgJheteroary CVCeJalkyl, or R 5 is R 14 , R 14 (C 1 -C 6 )alkyl or R 14 (C 3 -C 10 )cycloalkyl wherein R 14 is (C 2 -C 9 )heterocycloalkyl, (C 1 -C 6 )acylpιperazιno, (C 6 - C 10 )arylpιperazιno, (C 5 -C 9 )heteroarylpιperazιno, (C.,-C 6 )alkylpιperazιno, (C 8 -C^ary C,- C 6 )alkylpιperazιno, (Cs-C^heteroaryltC C^alkylpiperazino, morpholino, thiomorpholino, piperidmo, pyrrolidino, piperidyl, (C 1 -C 6 )alkylpιpeπdιnyl, (C 6 -C 10 )arylpιperιdyl, (C 5 - C 9 )heteroarylpιpeπdyl, (C 6 -C 1Q )aryl(C 1 -C 6 )alkylpιpeπdyl, (C 5 -C 9 )heteroaryl(C 1 -C 6 )alkyipιpeπdyl or (C CgJacylpipendyl, or R 6 is a group of the formula wherein w is 0, 1 or 2, x is O, 1 , 2 or 3, or R 5 is a group of the formula wherein g, h and j are each independently 0 to 3, F, K and P are each independently oxygen, S(0) d wherein d is 0, 1 or 2, NR 6 or CR 7 R S , R 6 is selected from the group consisting of hydrogen, (C r C 6 )alkyl, tnfluoromethyl, tπfluoromethyl(C 1 -C 6 )alkyl, (C r Cg)alkyl (difluoromethylene), (C 1 -C 3 )alkyl(dιfluoromethylene)(C 1 - C 3 )alkyl, (CrCgJalkoxyCCrCgJacyl, (CrCgJalkylaminoCCrCgJacyl, ((C 1 -C 6 )alkyl) 2 amιno(C 1 - C 6 )acyl, (C 6 -C 10 )aryl, (C 6 -C 9 )heteroaryl, (C 6 -C 10 )aryl(C l -C 6 )alkyl, (C β -C 10 )aryl(C 6 -C 10 )aryl, (C 6 -C 10 )aryl(C 6 -C 10 )aryl(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 3 - C 6 )cycloalkyl(C 1 -C 6 )alkyl, hydroxy(C 2 -C 6 )alkyl, (C 1 -C 6 )acyloxy(C 2 -Cg)alkyl, (C r C 6 )alkoxy(C 2 - C 6 )alkyl, pιperazιnyl(C r C 6 )alkyl, (C r C 6 )acylamιno(C r C 6 )alkyl, (C 6 -C 10 )aryl(C 1 -C 6 )alkoxy(C 1 - C 6 )alkyl, (C 6 -C 9 )heteroaryl(C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl l (C l -C 6 )alkylthιo(C 1 -C 6 )alkyl (C 6 - C 10 )arylthιo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylsulflnyl(C 1 -C 6 )alkyl, (C 6 -C 10 )arylsulfinyl(C l -C β )alkyl, (C r C 6 )alkylsulfonyl(C r C 6 )alkyl, (Cs-C arylsulfony C^C^alkyl, amιno(C 1 -C 6 )alkyl, (C,- C 6 )alkylamιno(C 1 -Cg)alkyl, ((C 1 -Cg)alkyl) 2 amιno(C 1 -C 6 )alkyl, R 13 CO(C r C 6 )alkyl wherein R 13 is R 0 O or R 20 R 21 N wherein R 20 and R 21 are each independently selected from the group consisting of hydrogen, (Chalky!, (C 6 -C 10 )aryl(C r C 6 )alkyl or (Cj-CgJheteroary CVCgJalkyl, or R 14 (C 2 - C 6 )alkyl wherein R 14 is (C 1 -C 6 )acylpιperazιno, (C 6 -C 10 )arylpιperazιno, (C 5 - C 9 )heteroarylpιperazιno, (C 6 -C 10 )aryl(C 1 -C 6 )alkylpιperazιno, (C 5 - Cg)heteroaryl(C r C 6 )alkylpιperazιno, morpholino, thiomorpholino, piperidmo, pyrrolidino, piperidyl, (C 6 -C 10 )arylpιpeπdyl, (C 5 -Cg)heteroarylpιperιdyl, (C 8 -C ary C,- C 6 )alkylpiperidyl, (C 5 -C 9 )heteroaryl(C 1 -Cg)alkylpιperιdyl, (C r C 6 )alkoxyacyl, (C 1 -C 6 )alkylamιnoaryl, ((C 1 -C 6 )alkyl 2 amιnoacyl or (C r C 6 )acylpipendyl, R 7 and R 8 are each independently selected from the group consisting of hydrogen, (C r C 6 )alkyl, ammo, hydroxy, (C r C 6 )alkoxy, (C 1 -C 6 )alkylamιno, ((C 1 -Cg)alkyl)amιno, (C r C 6 )acylamιno, (C C^acy C T C^alkylammo, carboxy, (C r C 6 )alkoxyacyl, (C 1 -C 6 )alkylamιnoacyl, ((C r C 6 )alkyl) 2 amιnoacyl, aminoacyl, tnfluoromethyl, tπfluoromethy C rCeJalkyl, (C r C 6 )alkyl (difluoromethylene), (C 1 -C 3 )alkyl(dιfluoromethylene)(C 1 -C 3 )alkyl, (C 6 -C 10 )aryl, (C 5 -C 8 )heteroaryl, (C 6 -C l0 )aryl(C 1 -Cg)alkyl, (Cs-CgJheteroary CrCgJalk l, (C 6 -C 10 )aryl(C β -C 10 )aryl, (C 6 -C 10 )aryl(C 6 - C 10 )aryl(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl(C 1 -Cg)alkyl, hydroxy(C 1 -C 6 )alkyl, (C r Cg)acyloxy(C 1 -C 6 )alkyl, (C 1 -Cg)alkoxy(C 1 -C 6 )alkyl, pιperazιnyl(C 1 -C 6 )alkyl, (C 1 -C 6 )acylamιno(C 1 - C 6 )alkyl, piperidyl, (C 1 -Cg)alkylpιpeπdyl, (Cs-C 10 )aryl(C 1 -Cg)alkoxy(C 1 -C 6 )alkyl, (C 5 - C 9 )heteroaryl(C 1 -C 6 )alkoxy(C l -C 6 )alkyl, (C 1 -C 6 )alkylthιo(C 1 -C 6 )alkyl, (C 6 -C 10 )arylthιo(C 1 -C 6 )alkyl, (C CeJalkylsulfiny CrCeJalkyl, (C 6 -C 10 )arylsulfinyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylsulfonyl(C 1 -C 6 )alkyl, (C 6 -C 10 )arylsulfonyl(C 1 -C 6 )alkyl, amιno(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylamιno(C 1 -C 6 )alkyl, ((C r C 6 )alkyl) 2 amιno(C 1 -C 6 )alkyl, R 13 CO(C 1 -C 6 )alkyl or R 13 CO(C 3 -C 10 )cycloalkyl wherein R 13 is R 20 O or R 20 R 21 N wherein R 20 and R 21 are each independently selected from the group consisting of hydrogen, (C r C 6 )alkyl, (C 6 -C 10 )aryl(C C 6 )alkyl or (C 5 -C 9 )heteroaryl(C r C 6 )alkyl, R 14 , R 14 (C r C 6 )alkyl or R 14 (C 3 -C 10 )cycloalkyl wherein R 14 is (C 1 -C 6 )acylpιperazιno, (C 6 -C 10 )arylpιperazιno, (C 5 -C 9 )heteroarylpιperazιno, (C 1 -C 6 )alkylpιperazιno, (C 6 -C 10 )aryl(C 1 -C 6 )alkylpιperazιno, (C 5 - Cg)heteroaryl(C 1 -C 6 )alkylpιperazιno, morpholino, thiomorpholino, piperidmo, pyrrolidino, piperidyl, (C 1 -C 6 )alkylpιpeπdyl, (C 6 -C 10 )arylpιpeπdyl, (C 6 -Cg)heteroarylpιpeπdyl, (C 6 -C 10 )aryl(C r C 6 )alkylpιpeπdyl, (C 5 -C 9 )heteroaryl(C 1 -C 6 )alkylpιpeπdyl or (C 1 -C β )acylpιperιdyl, or a group of the formula wherein p is 0, 1 , 2 or 3, and Z is hydroxy, (C r C 6 )alkoxy or NR 1 R 2 wherein R 1 and R 2 are each independently selected from the group consisting of hydrogen, (C 1 -C 6 )alkyl, piperidyl, (C r C 6 )alkylpιperιdyl, (C 6 - C 10 )arylpιpeπdyl, (C 5 -C 9 )heteroarylpιpeπdyl, (C 6 -C 10 )aryl(C 1 -C 6 )alkylpιperιdyl, (C 5 - CgJheteroary CrCgJalkylpipeπdyl, (C r C 6 )acylpiperidyl, (C 6 -C 10 )aryl, (C 5 -C 9 )heteroaryl, (C 6 - C 10 )aryl(C r C 6 )alkyl, (C 5 -C 9 )heteroaryl(C 1 -C 6 )alkyl, (C 6 -C 10 )aryl(C 6 -C 10 )aryl, (C 6 -C 10 )aryl(C 6 - C 10 )aryl(C r C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl(C r C 6 )alkyl, R 5 (C r C 6 )alkyl, (C r C 5 )alkyl(CHR 5 )(C 1 -C 6 )alkyl wherein R 5 is hydroxy, (C r C 6 )acyloxy, (C C 6 )a\koxγ, piperazmo, (C r C 6 )acylamιno, (C r C 6 )alkylthιo, (C 6 -C 10 )arylthιo, (C 1 -C 6 )alkylsulfinyl, (C 6 -C 10 )arylsulfinyl, (C r C 6 )alkylsulfoxyl, (C 6 -C 10 )arylsulfoxyl, ammo, (C,-C 6 )alkylamιno, ((C r C 6 )alkyl) 2 am o, (C,- C 6 )acylpιperazιno, (C 1 -C 6 )alkylpιperazιno, (C 6 -C 10 )aryl(C r C 6 )alkylpiperazino, (C 5 - C 9 )heteroaryl(C 1 -C 6 )alkylpιperazιno, morpholino, thiomorpholino, piperidmo or pyrrolidino, R 6 (C r C 6 )alkyl, (C 1 -C 6 )alkyl(CHR 6 )(C 1 -C 6 )alkyl wherein R 6 is piperidyl, (C 6 - C 10 )arylpιperιdyl, (C 6 -C 10 )aryl(C 1 -C 6 )alkylpιperιdyl, (C 5 -C 9 )heteroarylpιperιdyl or (C 5 - C 9 )heteroaryl(C 1 -C 6 )alkylpiperidyl, or R 1 is defined as OR 9 or S(0) q R 9 wherein q is 0, 1 or 2, and R 9 is selected from the group consisting of tπfluoromethyl(C 1 -C 6 )alkyl, (C r C 3 )alkyl(dιfluoromethylene)(C 1 -C 3 )alkyl, (C 3 -C 10 )cycloalkyl wherein the cycloalkyl group is optionally substituted by one to five carboxy, cyano, ammo, hydroxy, (C r C 6 ) alkoxy, halo, (C,- C 6 )alkyl S(0) m wherein m is 0, 1 or 2, R 15 R 15 NS(0) m wherein m is 0, 1 or 2 and R 15 and R 16 are each independently selected from hydrogen or (C.,-C 6 )alkyl, (C r C 6 )acyl, (C. | -C 6 )alkylamιno, amιno(C r C 6 )alkyl, (C r C 6 )alkoxy-CO-NH, R 15 R 16 N-CO-0-, R 15 R 16 N- CO-(C r C 6 )alkyl wherein R 15 and R 16 are as defined above, (C 2 -C 6 )alkenyl, (C 2 -C 6 ) alkynyl, (C,-C 6 )alkylamιno, amιno(C r C 6 )alkyl, hydroxy(C r C 6 )alkyl, (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C C 6 )acyloxy(C 1 -C 6 )alkyl, nitro, cyano(C r C 6 )alkyl, ^^(C T CeJalkyl, tnfluoromethyl, trιfluoromethyl(C 1 -C 6 )alkyl, (C 1 -C 6 )acylamιno, (C 1 -C 6 )alkoxy(C 1 -C 6 )acylamιno, amιno(C 1 - C 6 )acyl, (C 1 -C 6 )alkylamιno(C 1 -C 6 )acyl or ((C 1 -C 6 )alkyl) 2 amιno(C 1 -C 6 )acyl, (C 2 -C 6 )alkenyl, (C 2 - C 6 )alkynyl, (C 3 -C 10 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 6 )acyloxy(C 1 -C 6 )alkyl, (C 2 -C 6 )alkoxy(C r C 6 )alkyl, pιperazιnyl(C 1 -C 6 )alkyl, (C 1 -C 6 )acylamιno(C 1 -C 6 )alkyl, (C 6 -C 10 )aryl(C 1 -C 6 )alkoxy(C 1 - C 6 )alkyl, (C 5 -C 9 )heteroaryl(C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylthιo(C 1 -C 6 )alkyl, (C 6 - C 10 )arylthιo(C 1 -C 6 )alkyl, (C 6 -C 10 )arylsulfιnyl(C 1 -C 6 )alkyl, (C r C 6 )alkylsulfonyl(C 1 -C 6 )alkyl, (C 6 -C 10 )arylsulfonyl(C r C 6 )alkyl, amιno(C,-C 6 )alkyl, (C r C 6 )alkylamιno(C 1 -C 6 )alkyl, ((C 1 -C 6 )alkyl) 2 amιno, (C^CsJalkyl wherein the alkyl group is optionally substituted by one to five cyano, nitro, hydroxy, carboxy, (C r C 6 )acylamino, (C,- C 6 )alkoxy(C 1 -C 6 )acylamιno, amιno(C 1 -C 6 )acyl (C l -C 6 )alkylamιno(C 1 -C 6 )acyl or ((C r C 6 )alkyl) 2 amιno(C 1 -C 6 )acyl, R 13 CO(C,-C 6 )alkyl or R 13 CO(C 3 -C 10 )cycloalkyl wherein R 13 is R 20 O or R 20 R 21 N wherein R 20 and R 21 are each independently selected from the group consisting of hydrogen, (C CeJalkyl, (C 6 -C 10 )aryl(C 1 -C 6 )alkyl or R 14 , R 14 (C 1 - C 6 )alkyl or R 14 (C 3 -C 10 )cycloalkyl wherein R 14 is (C 2 -C 9 )heterocycloalkyl, (C|-C 6 )acylpιperazιno, (C 6 -C 10 )arylpιperazιno, (C 5 -C 9 )heteroarylpιperazιno, (C,-C 6 )alkylpιperazmo, (C 6 -C 10 )aryl(C r C 6 )alkylpιperazιno, (Cs-CgJheteroary C T C^alkylpiperazino, morpholino, thiomorpholino, piperidmo, pyrrolidino, piperidyl, (C r C 6 )alkylpιperιdιnyl, (C 6 -C 10 )arylpιperιdyl, (C 5 - Cg)heteroarylpιperιdyl, (C 6 -C 10 )aryl(C 1 -C 6 )alkylpιpeπdyl, (Cs-Cg^eteroary C C^alkylpipeπdyl or (C 1 -C 6 )acylpιperιdyl, or R 9 is a group of the formula wherein g, h and j are each independently 0 to 6, F, K and P are each independently oxygen, S(0) d wherein d is 0, 1 or 2, NR 6 or CR 7 R 8 wherein R 6 , R 7 and R 8 are as defined above, R 2 and R 3 are each independently selected from the group consisting of hydrogen, deuterium, ammo, halo, hydoxy, nitro, carboxy, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, tnfluoromethyl, tπfluoromethoxy, (C 1 -C 6 )alkyl, (C r C 6 )alkoxy wherein the alkyl or alkoxy groups are optionally substittued by one to three groups selected from halo, hydroxy, carboxy, ammo (C,- C 6 )alkylthιo, (C 1 -C 6 )alkylamιno, ((C 1 -C 6 )alkyl) 2 amιno, (C 5 -C 9 )heteroaryl, (C 2 - C 9 )heterocycloalkyl, (C 3 -C 9 )cycloalkyl or (C 6 -C 10 )aryl, or R 2 and R 3 are each independently (C 3 -C 10 )cycloalkyl, (C 3 -C 10 )cycloalkoxy, (C 1 -C 6 )alkylamιno, ((C 1 -C 6 )alkyl) 2 amιno, (C 6 - C 10 )arylamιno, (C.,-C 6 )alkylthιo, (C 6 -C 10 )arylthιo, (C C^alkylsulfinyl, (C 6 -C 10 )arylsulfιnyl, (C r C 6 )alkylsulfonyl, (C 6 -C 10 )arylsulfonyl, (C r C 6 )acyl, (C 1 -C β )alkoxy-CO-NH-, (C r C 6 )alkyamino- CO-, (C 5 -C 9 )heteroaryl, (C 2 -C 9 )heterocycloalkyl or (C 6 -C 10 )aryl wherein the heteroaryl, heterocycloalkyl and aryl groups are optionally substituted by one to three halo, (C r C 6 )alkyl, (C 1 -C 6 )alkyl-CO-NH-, (C C^alkoxy-CO-NH-, (C C^alkyl-CO-NrHC C^alkyl, (C 1 -C 6 )alkoxy- CO-NH-(C,-C 6 )alkyl, (CrC^alkoxy-CO-NI-HCrC^alkoxy, carboxy, carboxy(C 1 -C 6 )alkyl, carboxy(C r C 6 )alkoxy, benzyloxycarbonyl(C C 6 )alkoxy, (C 1 -C 6 )alkoxycarbonyl(C 1 -C 6 )alkoxy, (C 6 -C 10 )aryl, ammo, amιno(C 1 -C 3 )alkyl, C 6 )alkoxycarbonylamιno, (C T -CsJalkylammo, (C 1 -C 6 )alkylamιno(C 1 - C 6 )alkyl, ((C 1 -C 6 )alkyl) 2 amιno(C 1 -C 6 )alkyl, hydroxy, (C r C 6 )alkoxy, carboxy, carboxy(C 1 - C 6 )alkyl, (C 1 -C 6 )alkoxycarbonyl, (C 1 -C 3 )alkoxycarbonyl(C 1 -C 6 )alkyl, (C,-C 6 )alkoxy-CO-NH-, (C 1 -C 6 )alkyl-CO-NH-, cyano, (C 5 -Cg)heterocycloalkyl, amino-CO-NH-, NH-, ((C 1 -C 6 )alkyl) 2 amιno-CO-NH-, (C 6 -C 10 )arylamιno-CO-NH-, (C 6 -C 9 )heteroarylamιno-CO- NH-, (C r C 6 )alkylamino-CO-NH-(C r C 6 )alkyl, ((C ^alkyl^amino-CO- H^C CeJalkyl, (C 6 - C^arylamino-CO-NI-HCrCgJalkyl, (C 5 -C 8 )heteroarylamιno-CO-NH-(C 1 -C 6 )alkyl, (C r C 6 )alkylsulfonyl, (C^C^alkylsulfonylammo, (C 1 -C 6 )alkylsulfonylamιno(C 1 -C 6 )alkyi, (C 6 - C 10 )arylsulfonyl, (C 6 -C 10 )arylsulfonylamιno, (C 6 -C 10 )arylsulfonylamιno(C 1 -C 6 )alkyl, (C r C 6 )alkylsulfonylamιno, (C 1 -C 6 )alkylsulfonylamιno(C 1 -C 6 )alkyl, (C 5 -C 9 )heteroaryl or (C 2 - C 9 )heterocycloalkyl, with the proviso that when either R 4 and R 5 is hydrogen, the other of R 4 or R 5 cannot be (C 6 -C 10 )aryl or (C 6 -C 10 )aryl(C 1 -C 6 )alkyl, with the proviso that when R 4 is hydrogen, unsubstituted (CrC^alkyl or unsubstituted (C 3 -C 10 )cycloalkyl, R 5 cannot be (C 6 -C 10 )aryl(C 1 -C 6 )alkyl, R 20 and R 21 cannot be (C 5 - C 9 )heteroaryl(C 1 -C 6 )alkyl, and R 14 cannot be (C 2 -C 9 )heterocycloalkyl, morpholino, thiomorphlmo, piperidmo, pyrrolidino, piperidmyl or (C CeJalkylpipendinyl, with the proviso that the sp 2 and sp carbons of alkenyl or alkynyl cannot be substituted by hydroxy or ammo, with the proviso that when R 4 is hydrogen, R 5 cannot be ammo (C,-C 6 )alkyl, (C,- C 6 )alkyl, (C 1 -C 6 )alkylamιno(C l -C 5 )alkyl, ((C 1 -C β )alkyl) 2 amιno(C 1 -C 6 )alkyl, furanyl, (C,- C 6 )alkoxy(C 1 -C 6 )alkyl or carboxy(C r C 6 )alkyl, with the proviso that both R 4 and R 5 cannot both be hydroxy (C r C 6 )alkyl, with the proviso that when R 4 is (C 1 -C 6 )alkyl, R 5 cannot be (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl or carboxy(C 1 -C 6 )alkyl, and with the proviso that R 1 cannot be carboxy(C 1 -C 6 )alkylthιo or (C r C 6 )alkoxycarbonyl(C C 6 )alkylthιo The present invention also relates to the pharmaceutically acceptable acid addition salts of compounds of the formula I The acids which are used to prepare the pharmaceutically acceptable acid addition salts of the aforementioned base compounds of this invention are those which form non-toxic acid addition salts, ι_e_, salts containing pharmacologically acceptable anions, such as the hydrochlonde, hydrobromide, hydroiodide, nitrate, sulfate, bisulfate, phosphate, acid phosphate, acetate, lactate, citrate, acid citrate, tartrate, bitartrate, succmate, maleate, fumarate, gluconate, saccharate, benzoate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate and pamoate [ι_e_, 1 ,1'-methylene-bιs-(2-hydroxy-3- naphthoate)]salts The invention also relates to base addition salts of formula I The chemical bases that may be used as reagents to prepare pharmaceutically acceptable base salts of those compounds of formula I that are acidic in nature are those that form non-toxic base salts with such compounds Such non-toxic base salts include, but are not limited to those derived from such pharmacologically acceptable cations such as alkali metal cations (e_g_, potassium and sodium) and alkaline earth metal cations (e_g_, calcium and magnesium), ammonium or water- soluble amine addition salts such as N-methylglucamιne-(meglumιne), and the lower alkanolammomum and other base salts of pharmaceutically acceptable organic amines The term "alkyl", as used herein, unless otherwise indicated, includes saturated monovalent hydrocarbon radicals having straight, branched or cyclic moieties or combinations thereof The term "alkoxy", as used herein, includes O-alkyl groups wherein "alkyl" is defined above The term "halo", as used herein, unless otherwise indicated, includes fluoro, chloro, bromo or lodo The compounds of this invention may contain double bonds When such bonds are present, the compounds of the invention exist as cis and trans configurations and as mixtures thereof Unless otherwise indicated, the alkyl and alkenyl groups referred to herein, as well as the alkyl moieties of other groups referred to herein (e_g_, alkoxy), may be linear or branched, and they may also be cyclic (e_g_, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl) or be linear or branched and contain cyclic moieties Unless otherwise indicated, halogen includes fluorine, chlorine, bromine, and iodine (C 3 -C 10 )Cycloalkyl when used herein refers to cycloalkyl groups containing zero to two levels of unsaturation such as cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl cyclohexenyl, 1,3-cyclohexadιene, cycloheptyl, cyclohepten l, bιcyclo[3 2 1]octane, norbomanyl etc (C 2 -C 9 )Heterocycloalkyl when used herein refers to pyrrolidmyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydropyranyl, pyranyl, thiopyranyl, aziπdinyl, oxiranyl, methylenedioxyl, chromenyl, isoxazolidmyl, 1 ,3-oxazolιdιn-3-yl, isothiazohdinyl, 1,3-thιazolιdιn-3-yl, 1 ,2- pyrazolιdιn-2-yl, 1,3-pyrazolιdιn-1-yl, pipendinyl, thiomorpholmyl, 1 ,2-tetrahydrothιazιn-2-yl, 1,3- tetrahydrothιazιn-3-yl, tetrahydrothiadiazmyl, morpho nyl, 1 ,2-tetrahydrodιazιn-2-yl, 1,3- tetrahydrodιazιn-1-yl, tetrahydroazepinyl, piperazmyl, chromanyl, eta One of ordinary skill in the art will understand that the connection of said (C 2 -C 9 )heterocycloalkyl rings is through a carbon or a sp 3 hybridized nitrogen heteroatom (C 2 -C 9 )Heteroaryl when used herein refers to furyl, thienyl, thiazolyl, pyrazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrrolyl, tπazolyl, tetrazolyl, imidazolyl, 1,3,5-oxadιazolyl, 1 ,2,4- oxadiazolyl, 1,2,3-oxadιazolyl, 1,3,5-thιadιazolyl, 1,2,3-thιadιazolyl, 1,2,4-thιadιazolyl, pyridyl, pyπmidyl, pyrazmyl, pyridazmyl, 1 ,2,4-trιazιnyl, 1,2,3-tπazιnyl, 1,3,5-trιazιnyl, pyrazolo[3,4- b]pyrιdιnyl, cinnolmyl, pteπdinyl, puπnyl, 6J-dιhydro-5H-[1]pyrιndιnyl, benzo[b]thιophenyl, 5, 6, 7, 8-tetrahydro-quιnolιn-3-yl, benzoxazolyl, benzothiazolyl, benzisothiazolyl, benzisoxazolyl, benzimidazolyl, thianaphthenyl, isothianaphthenyl, benzofuranyl, isobenzofuranyl, iso dolyl, mdolyl, indolizmyl, mdazolyl, isoqumolyl, qumolyl, phthalazmyl, qumoxalinyl, quinazolmyl, benzoxazmyl, etc One of ordinary skill in the art will understand that the connection of said (C 2 - C 9 )heterocycloalkyl rings is through a carbon atom or a sp 3 hybridized nitrogen heteroatom (C 6 -C 10 )aryl when used herein refers to phenyl or naphthyl Compounds of formula (I) may be administered in a pharmaceutically acceptable form either alone or in combination with one or more additional agents which modulate a mammalian immune system or with antimflammatory agents These agents may include but are not limited to cyclosponn A (e g Sandιmmune lt:| or Neoral , rapamycm, FK-506 (tacrolimus), leflunomide, deoxyspergualm, mycophenolate (e g Cellcept ), azathiopnne (e g Imuran '), dac zumab (e g Zenapax OKT3 (e g Orthoclone 1 '), AtGam, aspirin, acetaminophen, ibuprofen, naproxen, piroxicam, and antiinflammatory steroids (e g prednisolone or dexamethasone) These agents may be administered as part of the same or separate dosage forms, via the same or different routes of administration, and on the same or different administration schedules according to standard pharmaceutical practice The compounds of this invention include all conformational isomers (e_g_, cis and trans isomers) and all optical isomers of compounds of the formula I (e_g_, enantiomers and diastereomers), as well as racemic, diastereomeπc and other mixtures of such isomers Preferred compounds of formula I include those wherein R 1 is NR 4 R 5 Other preferred compounds of formula I include those wherein R 4 is hydrogen, (C r C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl wherein the alkyl, alkenyl and alkynyl groups are optionally substituted by hydroxy, ammo, tnfluoromethyl, (C 1 -C 6 )acyloxy, ((C 1 -C 6 )alkyl) 2 amιno or (C 1 -C 6 )acylamιno, or R 4 is (C 3 -C 10 )cycloalkyl wherein the cycloalkyl group is optionally substituted by hydroxy, tnfluoromethyl or (C 1 -C 6 )acyloxy Other preferred compounds of formula I include those wherein R 5 is (C 3 -C 10 )cycloalkyl wherein the cycloalkyl group is optionally substituted by one to five deuterium, hydroxy, tnfluoromethyl, halo, (C r C 6 )alkyl, hydroxy(C r C 6 )alkyl, (C r C 6 )acyl, (C 1 -C 6 )alkylamιno(C 1 - C 6 )acyl, ((C 1 -C 6 )alkyl) 2 amιno(C 1 -C 6 )acyl, (C 1 -C 6 )acylamιno, (C T C^alkoxy-CO-NH, (C C 6 )alkylamιno-CO-, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )acylamιno(C 1 - C 6 )alkyl, R 15 S(0) m R 16 N, R 15 S(0) m R 16 N(C r C 6 )alkyl wherein m is 0, 1 or 2 and R 15 and R 16 are each independently selected from hydrogen or (C 1 -C 6 )alkyl Other preferred compounds of formula I include those wherein R 2 and R 3 are each independently selected from the group consisting of hydrogen, halo, ^-C^alky!, (C 2 - C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 3 -C 10 )cycloalkyl, (C 3 -C 10 )cycloalkoxy, (C 2 - C 9 )heterocycloalkyl, (C 5 -Cg)heteroaryl or (C 6 -C 10 )aryl Specific preferred compounds of formula I include the following 2-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrιmιdιn-4-yl)-amιno]-cyclohexyl}-propan-2- ol, 2-{3-[(2-Hydroxy-ethyl)-(7H-pyrrolo[2,3-d]pyrιmιdιn-4-yl)-amιno]-4-methyl-cyclohexyl}- propan-2-ol, 2-[(5-lsopropenyl-2-methyl-cyclohexyl)-(7H-pyrrolo[2,3-d]pyrιmιdιn-4-yl)-amιno]- ethanol, (5-lsopropenyl-2-methyl-cyclohexyl)-(7H-pyrrolo[2,3-d]pyrιmιdιn-4-yl)-(2,2,2-trιfluoro- ethyl)-amιne, 2-{4-Methyl-3-[(7H-pyrrolo[2,3-d]pyπmιdιn-4-yl)-(2,2,2-trιfluoro-ethyl)-ammo]- cyclohexyl}-propan-2-ol, 2-{4-Methyl-5-[methyl-(7H-pyrrolo[2,3-d]pyrιmιdιn-4-yl)-amιno]-cyclohex-3-enyl}- propan-2-ol, 2-[1-(7H-Pyrrolo[2,3-d]pyrιmιdιn-4-yl)-azetιdιn-3-yl]-propan-2-ol, 2-[1-(7H-Pyrrolo[2,3-d]pyrιmιdιn-4-yl)-azetιdιn-2-yl]-propan-2-ol, (5-Fluoro-7H-pyrrolo[2,3-d]pyrιmιdιn-4-yl)-(5-ιsopropenyl-2-methyl-cyclohexyl)-methyl- amme, 2-{3-[(5-Fluoro-7H-pyrrolo[2,3-d]pyπmιdιn-4-yl)-methyi-amιno]-4-methyl-cyclohexyl}- propan-2-ol, (2-Ethyl-4-ιsopropenyl-cyclopentyl)-methyl-(7H-pyrrolo[2,3-d]pyrιmιdιn-4-yl)-amιne, 2-{3-Ethyl-4-[methyl-(7H-pyrrolo[2,3-d]pyπmιdιn-4-yl)-amιno]-cyclopentyl}-propan-2-ol, 2-{3-Ethyl-4-[(2-hydroxy-ethyl)-(7H-pyrrolo[2,3-d]pyrιmιdιn-4-yl)-amιno]-cyclopentyl}- propan-2-ol, 2-[(2-Ethyl-4-ιsopropenyl-cyclopentyl)-(7H-pyrrolo[2,3-d]pyrιmιdιn-4-yl)-amιno]- ethanol, (5-(S)-lsopropenyl-2-methyl-cyclohexyl)-methyl-(7H-pyrrolo[2,3-d]pyrιmιdιn-4-yl)- amme, 3-Methyl-8-(7H-pyrrolo[2,3-d]pyrιmιdιn-4-yl)-8-aza-bιcyclo[3 2 1]octan-3-ol, 2-[Cycloheptyl-(7H-pyrrolo[2,3-d]pyrιmιdιn-4-yl)-amιno]-ethanol, 2-[Cyclooctyl-(7H-pyrrolo[2,3-d]pyrιmιdιn-4-yl)-amιno]-ethanol, Bιcyclo[2 2 1]hept-2-yl-methyl-(7H-pyrrolo[2,3-d]pyrιmιdιn-4-yl)-amιne, and 4-Pιperιdιn-1-yl-5-m-tolyl-7H-pyrrolo[2,3-d]pyrιmιdιne The present invention also relates to a pharmaceutical composition for (a) treating or preventing a disorder or condition selected from organ transplant rejection, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia, and other autoimmune diseases or (b) the inhibition of protein tyrosine kinases or Janus Kinase 3 (JAK3) in a mammal, including a human, comprising an amount of a compound of formula I or a pharmaceutically acceptable salt thereof, effective in such disorders or conditions and a pharmaceutically acceptable carrier The present invention also relates to a pharmaceutical composition for (a) treating or preventing a disorder or condition selected from organ transplant rejection, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia, and other autoimmune diseases or (b) the inhibition of protein tyrosine kinases or Janus Kinase 3 (JAK3) in a mammal, including a human comprising an amount of a compound of formula I or a pharmaceutically acceptable salt thereof, alone or in combination with T-cell immunosuppressant or antimflammatory agents, effective in such disorders or conditions and a pharmaceutically acceptable carrier The present invention also relates to a method for the inhibition of protein typrosme kinases or Janus Kinase 3 (JAK3) in a mammal, including a human, comprising administering to said mammal an effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof The present invention also relates to a method for treating or preventing a disorder or condition selected from organ transplant rejection, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia, and other autoimmune diseases in a mammal, including a human, comprising administering to said mammal an amount of a compound of formula I or a pharmaceutically acceptable salt thereof, effective in treating such a condition The present invention also relates to a method for the inhibition of protein typrosme kinases or Janus Kinase 3 (JAK3) in a mammal, including a human, comprising administering to said mammal an effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof, alone or in combination with T-cell immunosuppressant or antimflammatory agents The present invention also relates to a method for treating or preventing a disorder or condition selected from organ transplant rejection, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia, and other autoimmune diseases in a mammal, including a human, comprising administering to said mammal an amount of a compound of formula I or a pharmaceutically acceptable salt thereof, alone or in combination with T-cell immunosuppressant or antiinflammatory agents, effective in treating such a condition. Detailed Description of the Invention The following reaction Schemes illustrate the preparation of the compounds of the present invention Unless otherwise indicated R 1 , R 2 , R 3 and R 9 in the reaction Schemes and the discussion that follow are defined as above SCHEME 1 SCHEME2 SCHEME3 SCHEME4 III SCHEME5 SCHEME6 In reaction 1 of Scheme 1_, the 4-chloropyrrolo[2,3-d]pyrιmιdιne compound of formula XVII is converted to the corresponding compound of formula XVI, wherein R is benzenesulfonyl or benzyl, by treating XVII with benzenesulfonyl chloride, benzylchloπde or benzylbromide in the presence of a base, such as sodium hydride or potassium carbonate, and a polar aprotic solvent, such as dimethylformamide or tetra hydrofu ran The reaction mixture is stirred at a temperature between about 0°C to about 70°C, preferably about 30°C, for a time period between about 1 hour to about 3 hours, preferably about 2 hours In reaction 2 of Scheme 1_, the 4-chloropyrrolo[2,3-d]pyrιmιdιne compound of formula XVI is converted to the corresponding 4-amιnopyrrolo[2,3-d]pyrιmιdιne compound of formula XV by coupling XVI with an amine of the formula HNR R 5 The reaction is carried out in an alcohol solvent, such as tert-butanol, methanol or ethanol, or other high boiling organic solvents, such as dimethylformamide, 1 ,4-dιoxane or 1 ,2-dιchloroethane, at a temperature between about 60°C to about 120°C, preferably about 80°C Typical reaction times are between about 2 hours to about 48 hours, preferably about 16 hours In reaction 3 of Scheme 1_, removal of the protecting group from the compound of formula XV, wherein R is benzenesulfonyl, to give the corresponding compound of formula I, is carried out by treating XV with an alkali base, such as sodium hydroxide or potassium hydroxide, in an alcohol solvent, such as methanol or ethanol, or mixed solvents, such as alcohol/tetrahydrofuran or alcohol/water The reaction is carried out at room temperature for a time period between about 15 minutes to about 1 hour, preferably 30 minutes Removal of the protecting group from the compound of formula XV wherein R is benzyl, is conducted by treating XV with sodium in ammonia at a temperature of about -78°C for a time period between about 15 minutes to about 1 hour In reaction 1 of Scheme 2, the 4-chloropyrrolo[2,3-d]pyπmιdιne compound of formula XXI, wherein R is hydrogen or benzenesulfonate, is converted to the 4-chloro-5- halopyrrolo[2,3-d]pyrιmιdιne compound of formula XX, wherein Y is chloro, bromo or lodo, by reacting XXI with N-chlorosuccinimide, N-bromosuccinimide or N-iodosuccmimide The reaction mixture is heated to reflux, in chloroform, for a time period between about 1 hour to about 3 hours, preferably about 1 hour Alternatively, in reaction 1 of Scheme 2, the 4- chloropyrrolo[2,3-d]pyrιmιdιne of formula XXI, wherein R is hydrogen, is converted to the corresponding 4-chloro-5-nιtropyrrolo[2,3-d]pyπmιdιne of formula XX, wherein Y is nitro, by reacting XXI with nitric acid in sulfuπc acid at a temperature between about -10°C to about 10°C, preferably about 0°C, for a time period between about 5 minutes to about 15 minutes, preferably about 10 minutes The compound of formula XXI, wherein Y is nitro, is converted to the corresponding 4-chloro-5-amιnopyrrolo[2,3-d]pyrιmιdιne of the formula XX, wherein Y is ammo, by reacting XXI under a variety of conditions known to one skilled in the art such as palladium hydrogenolysis or tιn(IV)chloπde and hydrochloric acid In reaction 2 of Scheme 2, the 4-chloro-5-halopyrrolo[2,3-d]pyrιmιdιne compound of formula XX, wherein R is hydrogen, is converted to the corresponding compound of formula XIX, wherein R 2 is (C^C^alkyl or benzyl, by treating XX with N-butyl thium, at a temperature of about -78°C, and reacting the dianion intermediate so formed with an alkylha de or benzylhalide at a temperature between about -78°C to room temperature, preferably room temperature Alternatively, the dianion so formed is reacted with molecular oxygen to form the corresponding 4-chloro-5-hydroxypyrrolo[2,3-d]pyπmιdιne compound of formula XIX, wherein R 2 is hydroxy The compound of formula XX, wherein Y is bromine or iodine and R is benzenesulfonate, is converted to the compound of formula XIX, wherein R 2 is (C 6 -C 12 )aryl or vinyl, by treating XX with N-butyllithium, at a temperature of about -78°C, followed by the addition of zinc chloride, at a temperature of about -78°C The corresponding organo zinc intermediate so formed is then reacted with aryliodide or vinyl iodide in the presence of a catalytic quantity of palladium The reaction mixture is stirred at a temperature between about 50°C to about 80°C, preferably about 70°C, for a time period between about 1 hour to about 3 hours, preferably about 1 hour In reaction 3 of Scheme 2, the compound of formula XIX is converted to the corresponding compound of formula XVI by treating XIX with N-butyllithium, lithium diisopropylam e or sodium hydride, at a temperature of about -78°C, in the presence of a polar aprotic solvent, such as tetra hydrofu ran The anionic intermediate so formed is further reacted with (a) alkylhahde or benzylhalide, at a temperature between about -78°C to room temperature, preferably -78 °C, when R 3 is alkyl or benzyl, (b) an aldehyde or ketone, at a temperature between about -78°C to room temperature, preferably -78°C, when R 3 is alkoxy, and (c) zinc chloride, at a temperature between about -78°C to room temperature, preferably - 78°C, and the corresponding organozmc intermediate so formed is then reacted with aryliodide or vinyl iodide in the presence of a catalytic quantity of palladium The resulting reaction mixture is stirred at a temperature between about 50°C to about 80°C, preferably about 70°C, for a time peπod between about 1 hour to about 3 hours, preferably about 1 hour Alternatively, the anion so formed is reacted with molecular oxygen to form the corresponding 4-chloro-6-hydroxypyrrolo[2,3-d]pyrιmιdιne compound of formula XVI, wherein R 3 is hydroxy In reaction 1 of Scheme 3, the 4-chloropyrrolo[2,3-d]pyπmιdιne compound of formula XXI is converted to the corresponding compound of formula XXII, according to the procedure described above in reaction 3 of Scheme 2 In reaction 2 of Scheme 3, the compound of formula XXII is converted to the corresponding compound of formula XVI, according to the procedures described above in reactions 1 and 2 of Scheme 3 In reaction 1 of Scheme 4, the 4-chloropyrrolo[2,3-d]pyπmιdιne compound of formula XX is converted to the corresponding 4-amιnopyrrolo[2,3-d]pyπmιdιne compound of formula XXIV, according to the procedure described above in reaction 2 of Scheme 1_ In reaction 2 of Scheme 4, the 4-amιno-5-halopyrrolo[2,3-d]pyπmιdιne compound of formula XXIV, wherein R is benzenesulfonate and Z is bromine or iodine, is converted to the corresponding compound of formula XXIII by reacting XXIV with (a) arylboronic acid, when R 2 is aryl, in an aprotic solvent, such tetrahydrofuran or dioxane, in the presence of a catalytic quantity of palladium (0) at a temperature between about 50°C to about 100°C, preferably about 70°C, for a time period between about 2 hours to about 48 hours, preferably about 12 hours, (b) alkynes, when R 2 is alkynyl, in the presence of a catalytic quantity of copper (I) iodide and palladium (0), and a polar solvent, such as dimethylformamide, at room temperature, for a time period between about 1 hour to about 5 hours, preferably about 3 hours, and (c) alkenes or styrenes, when R 2 is vinyl or styrenyl, in the presence of a catalytic quantity of palladium in dimethylformamide, dioxane or tetrahydrofuran, at a temperature between about 80°C to about 100°C, preferably about 100°C, for a time period between about 2 hours to about 48 hours, preferably about 48 hours In reaction 3 of Scheme 4, the compound of formula XXIII is converted to the corresponding compound of formula XV, according to the procedure described above in reaction 3 of Scheme 2 In reaction 1 of Scheme 5, the 4-chloropyrrolo[2,3-d]pyπmιdιne compound of formula XVII is converted to the corresponding compound of formula XVI, wherein R is defined as above, according to the procedure described above in reaction 1 of Scheme 1 In reaction 2 of Scheme 5, the 4-chloropyrrolo[2,3-d]pyπmιdιne compound of formula XVI is converted the to the corresponding compound of formula XXV by coupling XVI with a compound of the formula, R 9 OH, in the presence of sodium hydroxide The reaction is carried out in a polar aprotic solvent, such as tetrahydrofuran, and heated to reflux for a time period between about 2 hours to about 4 hours, preferably about 3 hours Removal of the protecting group is carried out according to the procedure described above in reaction 3 of Scheme 1_ In reaction 1 of Scheme 6, the 4-chloropyrrolo[2,3-d]pyπmιdιne compound of formula XVII is converted to the corresponding compound of formula XXVI by coupling XVII with a compound of the formula, SR 9 , in the presence of potassium tert-butoxide and a polar aprotic solvent, such as tetrahydrofuran The resulting reaction mixture is heated to reflux for a time period between about 2 5 hours to about 5 hours, preferably about 3 5 hours The compound of formula XXVI may be further reacted with an oxidizing agent known to one of ordinary skill in the art, such as hydrogen peroxide, oxone, 3-chloroperoxybenzoιc acid or tert-butylperoxide to generate the corresponding 4- R 9 sulfinylpyrrolo[2,3-d]pyπmιdιne or 4- R 9 sulfonylpyrrolo compounds The compounds of the present invention that are basic in nature are capable of forming a wide variety of different salts with various inorganic and organic acids Although such salts must be pharmaceutically acceptable for administration to animals, it is often desirable in practice to initially isolate the compound of the present invention from the reaction mixture as a pharmaceutically unacceptable salt and then simply convert the latter back to the free base compound by treatment with an alkaline reagent and subsequently convert the latter free base to a pharmaceutically acceptable acid addition salt The acid addition salts of the base compounds of this invention are readily prepared by treating the base compound with a substantially equivalent amount of the chosen mineral or organic acid in an aqueous solvent medium or in a suitable organic solvent, such as methanol or ethanol Upon careful evaporation of the solvent, the desired solid salt is readily obtained The desired acid salt can also be precipitated from a solution of the free base in an organic solvent by adding to the solution an appropriate mineral or organic acid Those compounds of the present invention that are acidic in nature, are capable of forming base salts with various pharmacologically acceptable cations Examples of such salts include the alkali metal or alkaline-earth metal salts and particularly, the sodium and potassium salts These salts are all prepared by conventional techniques The chemical bases which are used as reagents to prepare the pharmaceutically acceptable base salts of this invention are those which form non-toxic base salts with the acidic compounds of the present invention Such non-toxic base salts include those derived from such pharmacologically acceptable cations as sodium, potassium calcium and magnesium, etc These salts can easily be prepared by treating the corresponding acidic compounds with an aqueous solution containing the desired pharmacologically acceptable cations, and then evaporating the resulting solution to dryness, preferably under reduced pressure Alternatively, they may also be prepared by mixing lower alkanolic solutions of the acidic compounds and the desired alkali metal alkoxide together, and then evaporating the resulting solution to dryness in the same manner as before In either case, stoichiometric quantities of reagents are preferably employed in order to ensure completeness of reaction and maximum yields of the desired final product The compositions of the present invention may be formulated in a conventional manner using one or more pharmaceutically acceptable carriers Thus, the active compounds of the invention may be formulated for oral, buccal, intranasal, parenteral (e g , intravenous, intramuscular or subcutaneous) or rectal administration or in a form suitable for administration by inhalation or insufflation The active compounds of the invention may also be formulated for sustained delivery For oral administration, the pharmaceutical compositions may take the form of, for example, tablets or capsules prepared by conventional means with pharmaceutically acceptable excipients such as binding agents (e g , pregelatinized maize starch, polyvinylpyrro done or hydroxypropyl methylcellulose), fillers (e g , lactose, microcrystalline cellulose or calcium phosphate), lubricants (e g , magnesium stearate, talc or silica), dismtegrants (e g , potato starch or sodium starch glycolate), or wetting agents (e_g_, sodium lauryl sulphate) The tablets may be coated by methods well known in the art Liquid preparations for oral administration may take the form of, for example, solutions, syrups or suspensions, or they may be presented as a dry product for constitution with water or other suitable vehicle before use Such liquid preparations may be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents (e g , sorbitol syrup, methyl cellulose or hydrogenated edible fats), emulsifying agents (e g , lecithin or acacia), non-aqueous vehicles (e g , almond oil, oily esters or ethyl alcohol), and preservatives (e g , methyl or propyl p-hydroxybenzoates or sorbic acid) For buccal administration, the composition may take the form of tablets or lozenges formulated in conventional manner The active compounds of the invention may be formulated for parenteral administration by injection, including using conventional catheteπzation techniques or infusion Formulations for injection may be presented in unit dosage form, e_g_, in ampules or in multi-dose containers, with an added preservative The compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulating agents such as suspending, stabilizing and/or dispersing agents Alternatively, the active ingredient may be in powder form for reconstitution with a suitable vehicle, e g , sterile pyrogen-free water, before use The active compounds of the invention may also be formulated in rectal compositions such as suppositories or retention enemas, e_g_, containing conventional suppository bases such as cocoa butter or other glycendes For intranasal administration or administration by inhalation, the active compounds of the invention are conveniently delivered in the form of a solution or suspension from a pump spray container that is squeezed or pumped by the patient or as an aerosol spray presentation from a pressurized container or a nebulizer, with the use of a suitable propellant, e g , dichlorodifluoromethane, tπchlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas In the case of a pressurized aerosol, the dosage unit may be determined by providing a valve to deliver a metered amount The pressurized container or nebulizer may contain a solution or suspension of the active compound Capsules and cartridges (made, for example, from gelatin) for use in an inhaler or insufflator may be formulated containing a powder mix of a compound of the invention and a suitable powder base such as lactose or starch A proposed dose of the active compounds of the invention for oral, parenteral or buccal administration to the average adult human for the treatment of the conditions referred to above (e g , rheumatoid arthritis) is 0 1 to 1000 mg of the active ingredient per unit dose which could be administered, for example, 1 to 4 times per day Aerosol formulations for treatment of the conditions referred to above (e g , asthma) in the average adult human are preferably arranged so that each metered dose or "puff of aerosol contains 20 μg to 1000 μg of the compound of the invention The overall daily dose with an aerosol will be within the range 0 1 mg to 1000 mg Administration may be several times daily, for example 2, 3, 4 or 8 times, giving for example, 1 , 2 or 3 doses each time A compound of formula (I) administered in a pharmaceutically acceptable form either alone or in combination with one or more additional agents which modulate a mammhan immune system or with antimflammatory agents, agents which may include but are not limited to cyclosponn A (e g Sandimmune' 11 or Neoral , rapamycm, FK-506 (tacro mus), leflunomide, deoxyspergua n, mycophenolate (e g Cellcept , azathiopπne (e g Imuran ), daclizumab (e g Zenapax '), OKT3 (e g Orthocolone r '). AtGarn, aspirin, acetaminophen, ibuprofen, naproxen, piroxicam, and antiinflmmatory steroids (e g prednisolone or dexamethasone), and such agents may be administered as part of the same or separate dosage forms, via the same or different routes of administration, and on the same or different administration schedules according to standard pharmaceutical practice FK506 (Tacrohmus) is given orally at 0 10-0 15 mg/kg body weight, every 12 hours, within first 48 hours postoperative Does is monitored by serum Tacrohmus trough levels Cyclosponn A (Sandimmune oral or intravenous formulation, or Neoral , oral solution or capsules) is given orally at 5 mg/kg body weight, every 12 hours within 48 hours postoperative Dose is monitored by blood Cyclosponn A trough levels The active agents can be formulated for sustained delivery according to methods well known to those of ordinary skill in the art Examples of such formulations can be found in United States Patents 3,538,214, 4,060,598, 4,173,626, 3,119,742, and 3,492,397 The ability of the compounds of formula I or their pharmaceutically acceptable salts to inhibit Janus Kinase 3 and, consequently, demonstrate their effectiveness for treating disorders or conditions characterized by Janus Kinase 3 is shown by the following in vitro assay tests Biological Assay JAK3 (JH1 GST) Enzymatic Assay The JAK3 kinase assay utilizes a protein expressed in baculovirus-mfected SF9 cells (a fusion protein of GST and the catalytic domain of human JAK3) purified by affinity chromatography on glutathione-Sepaharose The substrate for the reaction is poly-Glutamic acid-Tyrosme (PGT (4 1), Sigma catalog # P0275), coated onto Nunc Maxi Sorp plates at 100 μg/ml overnight at 37°C The morning after coating, the plates are washed three times and JAK3 is added to the wells containing 100 μl of kinase buffer (50 mM HEPES, pH 7 3, 125 mM NaCI, 24 mM MgCI2)+ 0 2 uM ATP + 1 mM Na orthovanadate ) The reaction proceeds for 30 minutes at room temperature and the plates is washed three more times The level of phosphorylated tyrosine in a given well is quantitated by standard ELISA assay utilizing an anti-phosphotyrosine antibody (ICN PY20, cat #69-151-1) DND 39/IL-4 Cellular Assay for JAK3 kinase Inhibitors The DND 39/IL-4 assay is designed to find inhibitors of JAK3 kinase activity which would be prime candidates for immunosupressive and/or allergy The assay uses a B-cell line called DND39 which has had the luciferase gene driven by the germ line IgE promoter stably integrated into one of the chromosomes When these cells are stimulated with IL-4, the kinase JAK3, which is associated with the IL-4 receptor, phosphorylates the signal transducer STAT6 STAT6 then blinds to the germ ne IgE promoter and starts transcription of the luciferase gene Luciferase is measured in a lysate of these cells using the Promega luciferase assay reagent system Note DND39 cells are grown in RPMI 1640 supplemented with 10% heat inactivated FCS, 2 mM L-Glutamme, and 100 units/ml Pen /Strep The cells are maintained from 1x10 s to 1x10 6 cells/ml Split to 1x10 5 on Friday, cells will be at about 1x10 6 on Monday Then split 1 2 during the week keeping 200 ml in a flask as needed 3x10 5 DND39 cells are plated in 100 μl of RPMI 1640 supplemented with 1 % heat inactivated FCS, 2 mM L-glutamine, and 100 units/ml Pen/Step in a 96 well Vee bottom plate (Nunc) Compounds are diluted serially 1 2 in DMSO starting at 4mM to 1 9μM In a 96 well polypropylene plate, changing tips after each dilution Then 5μl of each dilution are added to 500μl of RPMI/1% serum in a 96 tube rack 125 μL of the compound dilutions are added to the cells and incubated at 37°C, 5% C0 2 for one hour After one hour, 25 μl of 25 ng/ml IL-4 is added to the cells and mixed Final concentration of IL-4 is 2 5 ng/ml and final concentration of compound is from 20 μM to 156 nM The cells are then incubated overnight 16-18 hours The plate is then centπfuged at 2500-3000 RPM in a table top centrifuge for 5 minutes The culture supernatant is carefully removed by aspiration with an 8 well maifold 100 μl of PBS with calcium and magnesium is added to the pelletted cells The cells are resuspended in the PBS and transferred to a Packard white OptiPlate 100 μl of Packard's LucLite reagent is added to the wells of the OptiPlate The following Examples illustrate the preparation of the compounds of the present invention but it is not limited to the details thereof Melting points are uncorrected NMR data are reported in parts per million (δ) and are referenced to the deuterium lock signal from the sample solvent (deuteπochloroform unless otherwise specified) Commercial reagents were utilized without further purification THF refers to tetrahydrofuran DMF refers to N,N-dιmethylformamιde Low Resolution Mass Spectra (LRMS) were recorded on either a Hewlett Packard 5989®, utilizing chemical lonization (ammonium), or a Fisons (or Micro Mass) Atmospheric Pressure Chemical lonization (APCI) platform which uses a 50/50 mixture of acetonitnle/water with 0 1%> formic acid as the ionizing agent Room or ambient temperature refers to 20-25°C EXAMPLE 1 Cyclohexyl-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine METHOD A Cyclohexyl-methyl-amine To a solution of cyclohexanone (98 mg/1mmol) and acetic acid (120 mg/2 mmol) dissolved in 2 0 mL of 1 ,2-dιchloroethane was added 2 0 mL of a 2 M solution of methylamine in methanol and the resulting mixture stirred at room temperature for 4 h Polymer supported borohydπde (1 g/2 5 mmol) was added and the mixture stirred at room temperature for 1 h then filtered and concentrated to dryness in vacuo affording 66 mg ( 40%) of the title compound as the acetate salt H NMR (400 MHz)(CD 3 OD) δ 1 17 - 1 37 (m, 5H), 1 67 (br d, 1H, J = 12 5 Hz), 1 83 (br d, 2H, J = 18 7 Hz), 1 86 (s, 3H), 2 04 (br d, 2H, J = 10 2 Hz), 2 60 (s, 3H), 2 86 - 2 92 (m, 1H) METHOD B Cyclohexyl-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine A mixture of 200 mg (1 30 mmol) of 4-chloro-7H-pyrrolo[2,3-d]pyπmιdιne (prepared by the method of Davoll, J Am Chem Soc , (1960), 82, 131 ), the product from Method A (589 mg/5 21 mmol) and 3 mL of tert-butanol was stirred in a sealed tube at 100 °C for 24 h The reaction mixture was added to water , acidified to pH 1 with 1 N HCI (aq), washed twice with diethylether (ether) and basified to pH 14 with 1 N sodium hydroxide (NaOH) The resulting precipitate was filtered and dried in vacuo to obtain 263 mg (88%) of the title compound, mp 177-180 °C 1 H NMR (400 MHz, CDCI 3 ) δ 1 11-1 22 (m, 1H), 1 43-1 63 (m, 4H), 1 73 (br d, 1 H, J = 13 3 Hz), 1 83-1 90 (m, 4 H), 3 23 (s, 3H), 4 69 (br, 1 H), 6 53 (d, 1 H, J = 3 5 Hz), 7 03 (d, 1 H, J = 3 5 Hz), 8 30 (s, 1 H), 10 6 (br, 1 H) LRMS 231 (M+1) The title compounds of Examples 2-84 were prepared by a method analogous to that described in Example 1 EXAMPLE 2 Benzyl-ethyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Benzylethylamine Melting Point 170 - 172°C, LRMS 252 3 EXAMPLE 3 Methyl-(S)-1-phenyl-ethyl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Methyl-(S)-1-ρhenylethylamιne Melting Point 131°C, LRMS 253 EXAMPLE 4 Cyclopentyl-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Cyclopentylmethylamine LRMS 217 3 EXAMPLE 5 Allyl-cyclohexyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Allylcyclohexylamme LRMS 257 EXAMPLE 6 Allyl-cyclopentyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Allyicyclopentylamine Melting Point 173 - 175°C, LRMS 243 EXAMPLE 7 Allyl-cyclopentyl 7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Cyclohexylethylamine LRMS 245 3 EXAMPLE 8 (1-Cyclorιexyl-ethyl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine (l-Cyclohexylethyl)methylamιne LRMS 259 4 EXAMPLE 9 Cycloheptyl-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Cycloheptylmethylamine Melting Point 177 - 178°C, LRMS 245 3 EXAMPLE 10 Cyclooctyl-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Cyclooctylmethylamine Melting Point 188 - 189°C, LRMS 259 4 EXAMPLE 11 Methyl-(3-methyl-cyclohexyl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Methyl-(3-methylcyclohexyl)amιne LRMS 245 3 EXAMPLE 12 Methyl-(4-methyl-cyclohexyl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Methyl-(4-methylcyclohexyl)-amιne LRMS 245 3 EXAMPLE 13 Methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-(3,3,5-trimethyl-cyclohexyl)-amine Methyl-(3,3,5-tπmethylcyclohexyl)-amιne LRMS 273 4 EXAMPLE 14 Cycloheptyl-ethyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Cycloheptylethylamme Melting Point 168 - 169°C, LRMS 259 4 EXAMPLE 15 Cyclooctyl-et yl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Cyclooctylethylamme Melting Point 155 - 156°C, LRMS 2734 EXAMPLE 16 [1-(4-Chloro-phenyl)-propyl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine [1-(4-Chlorophenyl)-propyl]methylamιne LRMS 301 7 EXAMPLE 17 [2-(2-Methoxy-phenyl)-1-methyl-ethyl]-methyl-(7H-pyrrolo[2,3-d]pyrirrιidin-4-yl)- amine [2-(2-Methoxy-phenyl)-1-methyl-ethyl]-methylamιne LRMS 297 4 EXAMPLE 18 (Decahydro-naphthalen-1-yl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Decahydronaphthalen-1-yl-methylamιne LRMS 2854 EXAMPLE 19 Cyclodecyl-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Cyclodecylmethylamine LRMS 287 1 EXAMPLE 20 Cyclononyl-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Cyclononylmethyl LRMS 273 1 EXAMPLE 21 2-[Cyclopentyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-ethanol 2-Cyclopentylamιnoethanol Melting Point 156 - 158°C, LRMS 247 3 EXAMPLE 22 Cycloheptyl-(2-methoxy-ethyl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Cycloheptyl-(2-methoxy-ethyl)amιne LRMS 289 EXAMPLE 23 Cycloheptyl-cyclopropyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Cycloheptyl-cyclopropylamme LRMS 271 4 EXAMPLE 24 Cycloheptyl-cyclopropyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-ethanol Cyclohexylaminoethanol. Melt Point: 200 - 201 C C; LRMS: 261.3. EXAMPLE 25 Cyclooctyl-(2-methoxy-ethyl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Cyclooctyl-(2-methoxy-ethyl)amine. LRMS: 303. EXAMPLE 26 sec-Butyl-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine sec-Butyl-methylamine. Melting Point: 146 - 148°C; LRMS: 205. EXAMPLE 27 2-[Methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-1-phenyl-propan-1-ol 2-Methyl-1- phenyl-propan-1-ol. LRMS: 283, 265. EXAMPLE 28 [2-(4-Chloro-phenoxy)-1-methyl-ethyl]-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)- amine [2-(4-Chlorophenoxy)-1-methylethyl]-methylamine. Melting Point: 139 - 141°C; LRMS: 319, 317, 189. EXAMPLE 29 N-Cyclohexyl-N',N'-dimethyl-N-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-propane-1,3- diamine N-Cyclohexyl-N'.N'-dimethyl propane-1 ,3-diamine. LRMS: 302.4. EXAMPLE 30 N-{2-[Cyclohexyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-ethyl}-acetamide N-Cyclohexylaminoethyl acetamide. LRMS: 302.4. N- EXAMPLE 31 2-[Cycloheptyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-ethanol 2-Cyclohexylaminoethanol. Melting Point: 69 - 72°C; LRMS: 275.4. EXAMPLE 32 2-[Cyclooctyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-ethanol 2-Cyclooctylaminethanol. Melting Point: 66 - 77°C; LRMS: 289.4. EXAMPLE 33 (3,5-Dimet yl-cyclohexyl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine (3,5-Dimethylcyclohexyl)methylamine. LRMS: 259.4. EXAMPLE 34 2-[Benzyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-ethanol 2-Benzylaminoethanol. LRMS: 269, 251. EXAMPLE 35 3-[Cyclopen.yl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-propan-1-ol 3-Cyclopentylamιno-propan-1-ol Melting Point 162 - 164°C, LRMS 261 3 EXAMPLE 36 3-[Cycloheptyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-propan-1-ol 3-Cycloheptylamιnopropan-1-ol Melting Point 62 - 66°C, LRMS 2894 EXAMPLE 37 2-[(Decahydro-naphthalen-2-yl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-ethanol 2-Decahydronaphthalen-2-yl-amιnoethanol Melting Point 75°C, LRMS 315 EXAMPLE 38 2-[(1-Ethyl-propyl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-ethanol 2-(1-Ethylpropyl)amιne ethanol Melting Point 49 - 53°C, LRMS 249 3 EXAMPLE 39 1-[Cyclohexyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-butan-2-ol Cyclohexylamιno-butan-2-ol LRMS 289 EXAMPLE 40 Bicyclo[2.2.1]hept-2-yl-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Bιcyclo[2 2 1]hept-2-yl-methylamιne LRMS 243 EXAMPLE 41 2(S)-{[Cyclohexyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-methyl}- cyclohexanol 2-(Cyclohexylamιne)methylcyclohexanol LRMS 329 EXAMPLE 42 2(R)-{[Cyclohexyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-methyl}- cyclohexanol 2-(Cyclohexylamιne)methylcyclohexanol LRMS 329 EXAMPLE 43 (2-Ethyl-cyclopentyl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine (2-Ethylcyclopentyl)methyl amine LRMS 287 EXAMPLE 44 Cyclononyl-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Cyclononylmethylamine LRMS 273 EXAMPLE 45 Methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-(2,4,4-trimethyl-cyclopentyl)-amιne Methyl-2,4,4-trimethyl-cyclopentyl)-amine LRMS 259 EXAMPLE 46 (3-Ethyl-cyclopentyl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine (3-Ethyl-cyclopentyl)methylamιne LRMS 245 EXAMPLE 47 (2,5-Dimethyl-cyclohexyl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine (2,5-Dιmethylcyclohexyl)methyl-amιne LRMS 259 EXAMPLE 48 (3,4-Dimethyl-cyclohexyl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine (3,4-Dιmethylcyclohexyl)methylamιne LRMS 259 EXAMPLE 49 (4-lsopropyl-cyclohexyl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine (4-lsopropylcyclohexyl)methylamιne LRMS 273 EXAMPLE 50 (Deca ydro-nap thalen-1-yl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine (Decahydronaphthalen-l-yl)methylamιne LRMS 285 EXAMPLE 51 (2,2-Dimethyl-cyclohexyl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine (2,2-Dιmethylcyclohexyl)methylamιne LRMS 259 EXAMPLE 52 (2-lsopropyl-5-methyl-cyclohexyl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)- amine (2-lsopropyl-5-methylcyclohexyl)methylamιne LRMS 287 EXAMPLE 53 Met yl-(3-methyl-cyclopentyl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Methyl-(3-methyl-cyclopentyl)amιne LRMS 231 EXAMPLE 54 (1-Benzyl-piperidin-4-yl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine (1-Benzylpιpeπdιn-4-yl)methylamιne LRMS 322 EXAMPLE 55 (4-tert-Butyl-cyclohexyl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine (4-tert-Butylcyclohexyl)methylamιne LRMS 287 EXAMPLE 56 lndan-1-yl-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine lndan-1-yl-methylamιne LRMS 265 EXAMPLE 57 (4-Ethyl-cyclo exyl)-metrιyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine (4-Ethylcyclohexyl)methylamιne LRMS 259 EXAMPLE 58 Methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-(1,2,3,4-tetrahydro-naphthalen-2-yl)- amine Methyl-1 ,2,3,4-tetrahydro-naphthalen-2-yl)-amιne LRMS 279 EXAMPLE 59 Bicyclo[3.2.1]oct-2-yl-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Bιcyclo[3 2 1]oct-2-yl-methylamιne LRMS 257 EXAMPLE 60 Metrιyl-(octahydro-4,7-methano-inden-5-yl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)- amine Methyl-(octahydro-4J-methano-ιnden-5-yl)amιne LRMS 283 EXAMPLE 61 Bicyclo[2.2.1]hept-2-yl-met yl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Bιcyclo[22 1]hept-2-yl-methylamιne LRMS 243 EXAMPLE 62 (5-Chloro-indan-1-yl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine (5-Chloro-ιndan-1-yl)methylamιne LRMS 299 EXAMPLE 63 Adamantan-2-yl-met yl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Adamantan-2-yl-methylamιne LRMS 283 EXAMPLE 64 (Decahydro-naphthalen-2-yl)-methyl-(7H-pyrrolo[2,3-d]pyrimidιn-4-yl)-amine (Decahydro-naphthalen-2-yl)methylamιne LRMS 285 EXAMPLE 65 (3,5-Dimethyl-cyclohexyl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine (3,5-Dιmethylcyclohexyl)methylamιne LRMS 259 EXAMPLE 66 Bicyclo[3.3.1]non-9-yl-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Bιcyclo[3 3 1]non-9-yl-methylamιne LRMS 271 EXAMPLE 67 (1-lsopropyl-4-methyl-bicyclo[3.1.0]hex-3-yl)-methyl-(7H-pyrrolo[2,3- d]pyrimidin-4-yl)-amine (1-lsopropyl-4-methylbιcyclo[3 1 0]hex-3-yl)-methylamιne LRMS 285 EXAMPLE 68 Cyclobutyl-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Cyclobutylmethylamine. LRMS: 203. EXAMPLE 69 (2,2-Dimethyl-cyclopentyl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine (2,2-Dimethyl-cyclopentyl)methylamine. LRMS: 245. EXAMPLE 70 4-[Methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-cyclohexanecarboxylic acid ethyl ester 4-[Methylamino]cyclohexanecarboxylic acid. LRMS: 303. EXAMPLE 71 (2-lsopropyl-5-methyl-cyclohexyl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)- amine (2-lsopropyl-5-methyl-cyclohexyl)methylamine. LRMS: 287. EXAMPLE 72 (3,3-Dimethyl-cyclohexyl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine (3,3-Dimethyl-cyclohexyl)methylamine. LRMS: 259. EXAMPLE 73 1(S)-[Cyclohexyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-propan-2-ol 1-[Cyclohexylamino]-propan-2-ol. LRMS: 275.4. EXAMPLE 74 1(R)-[Cyclohexyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-propan-2-ol 1-[Cyclohexylamino]-propan-2-ol. LRMS: 275.4. EXAMPLE 75 3-[Cyclohexyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-propane-1,2-diol 3-[Cyclohexylamino]-propane-1,2-diol. LRMS: 291.4. EXAMPLE 76 2-[(Decahydro-naphthalen-1-yl)-(7H-pyrrolo[2,3-d]pyrimidin- -yl)-amino]-ethanol 2-[(Decahydro-naphthalen-1-yl) -amino]-ethanol. LRMS: 315.4. EXAMPLE 77 {2-[Cycloheptyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-ethyl}-carbamic acid tert-butyl ester 2-[(Cycloheptylamino)ethyl]carbamic acid. LRMS: 374.5. EXAMPLE 78 Methyl-(3-methyl-cyclohexyl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Methyl-(3-methylcyclohexyl)amine. LRMS: 359.4. EXAMPLE 79 Methyl-(2-methyl-cyclohexyl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Methyl-(2-methylcyclohexyl)amine. LRMS: 359.4. EXAMPLE 80 (2-Ethyl-cyclohexyl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine (2-Ethyl-cyclohexyl)methylamine. LRMS: 373.4. EXAMPLE 81 Methyl-(2-propyl-cyclohexyl)-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Methyl-(2-propylcyclohexyl)amine. LRMS: 387.4. EXAMPLE 82 (2,4-Dimethyl-cyclohexyl)-methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine (2,4-Dimethylcyclohexyl)methylamine. LRMS: 373.4. EXAMPLE 83 Methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-(2,5,5-trimethyl-cyclohexyl)-amine Methyl- (2,5,5-trimethylcyclohexyl)-amine. LRMS: 387.4. EXAMPLE 84 Methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-(2,2,5,5-tetramethyl-cyclohexyl)-amine Methyl-(2,2,5,5-tetramethylcyclohexyl)-amine. LRMS: 401. EXAMPLE 85 Cyclohexyl-methyl-(6-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Cyclohexylmethylamine. METHOD C 7-Benzenesulfonyl-4-chloro-7H-pyrrolo[2,3-d]pyrimidine In a flame-dried flask under nitrogen, 780 mg of 60 % sodium hydride ( 19 5 mmol) in mineral oil was added to 30 mL of dimethylformamide (DMF) and the resulting mixture cooled to 0 °C A solution of 2 0 g (13 0 mmol) of 4-chloro-7H-pyrrolo[2,3-d]pyπmιdιne in 10 mL of DMF was added slowly over a 5 mm period The reaction was stirred for 10 mm at which time generation of hydrogen (H 2 ) ceased Benzenesulfonylchloπde (1 7 mL/13 0 mmol) was added, the reaction warmed to room temperature and stirred for 1 h Water was added, and the resulting precipitate was filtered and dried in vacuo to obtain 3 4 g (89%) of the title compound as a crystalline solid, mp 163-167 °C METHOD D 7-Benzenesulfonyl-4-chloro-6-phenyl-7H-pyrrolo[2,3-d]pyrimidine In a flame-dried flask under nitrogen, 0 53 mL (3 79 mmol) of diisopropylamine were dissolved in 5 mL of tetrahydrofuran (THF) and the solution cooled to -78 °C n-Butylhthium (3 75 mmol as a 2 5 M solution in hexanes) was added and the resulting mixture brought to 0 °C with continued stirring for 10 mm The reaction mixture was again cooled to -78 °C and to this mixture added a solution of 1 0 g (3 40 mmol) of the product from Method C in 10 mL of THF over a 10 mm period The reaction mixture was stirred for 1 h at -78 °C, at which time, 8 2 mL (4 10 mmol) of a 0 5 M solution of zinc chloride in THF was added, the reaction mixture was brought to room temperature and stirred for 1 h lodobenzene (0 46 mL/4 11 mmol) and a suspension of 197 mg of tetrakιs(trιphenylphosphιne) palladium in 2 mL of THF were added The resulting mixture was stirred at reflux for 3 h , cooled to room temperature, and partitioned between dichloromethane and water The aqueous layer was acidified with 1 N HCI and extracted twice with dichloromethane The dichloromethane layers were combined, washed with 1 N HCI and brine, dried over magnesium sulfate (MgS0 4 ), filtered and concentrated in vacuo to obtain the title compound LRMS 370, 372 (M+2) METHOD E 4-Chloro-6-phenyl-7H-pyrrolo[2,3-d]pyrimidine The product from Method D was dissolved in 10 mL of THF and to this solution was added 5 0 mL of methanol and 1 0 g of NaOH The reaction mixture was stirred for 15 m , concentrated in vacuo and partitioned between a saturated aqueous solution of ammonium chloride (NH 4 CI) and ethyl acetate The resulting aqueous layer was extracted twice with ethyl acetate The ethylacetate layers were combined, washed with brine, dried over MgS0 4 , filtered and concentrated in vacuo The crude product was purified by silica-gel chromatography (1 5 ethyl- acetate/hexane) to obtain 0 59 g (76 %) of the title compound as a pale yellow solid, mp 145 °C (dec) LRMS 230, 232 (M+2) METHOD F Cyclohexyl-methyl-(6-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine The product from Method E (50 mg/0 218 mmol) was reacted with 0 12 mL of N- methylcyclohexylamine (0 920 mmol) as described in Method B The reaction mixture was concentrate in vacuo, methanol was added, and the resulting precipitate filtered to provide 7 mg (10%) of the title compound as a yellow solid 1 H NMR (400 MHz, CDCI 3 ) δ 1 18-1 25 (m, 1H), 1 47-1 66 (m, 4H), 1 75-1 90 (m, 5H), 3 30 (s, 3H), 4 74 (br, 1H), 6 79 (s, 1H), 7 32-7 36 (m, 1H), 747-7 51 (m, 2H), 7 77 (d, 2H, J = 7 9 Hz), 8 33 (s, 1H) LRMS 307 (M+1) The title compound of Example 86 was prepared by a method analogous to that described in Example 85 EXAMPLE 86 (1H-lndol-5-yl)-(6-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine IH-lndolamme LRMS 326 4 EXAMPLE 87 Cyclohexyl-methyl-(6-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Cyclohexylmethylamine METHOD G 7-Benzenesulfonyl-4-chloro-6-methyl-7H-pyrrolo[2,3-d]pyrimidine To flame-dried flask under N 2 was charged 0 57 ml (4 07 mmol) of dnsopropylamine and 5 0 mL of dry THF The solution was cooled to -78 °C and 1 63 mL (4 08 mmol) of a 2 5 M solution of n-butylhthium in hexanes added The resulting mixture was brought to 0 °C and stirred for 10 mm After cooling the mixture again to -78 °C, a solution of 1 0 g (340 mmol) of crude product from Method C m 10 mL of dry THF was added over a 10 mm period The resulting mixture was stirred for 1 h, at which time, 028 mL (4 50 mmol) of lodomethane were added The reaction mixture was stirred for 2 h, quenched with a saturated solution of NH 4 CI and warmed to room temperature The mixture was stirred for 5 mm , diluted with water and extracted three times with ethyl acetate The combined extracts were washed with brine, dried over MgS0 4 , filtered and evaporated in vacuo to obtain the title compound LRMS 308, 310 (M+2) METHOD H 4-Chloro-6-methyl-7H-pyrrolo[2,3-d]pyrimidine The product from Method G was deprotected as described in Method E The crude product was purified by tπturation with hexanes and dichloromethane to obtain 250 mg (44%) of the title compound as a yellow solid Mp 205 °C dec LRMS 168, 170 (M+2) METHOD I Cyclohexyl-methyl-(6-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine The product from Method H (50 mg/0 298 mmol) was reacted with 100 mg (0 883 mmol) of N-methylcyclohexylamine as described in Method B The reaction mixture was worked up as in Method B with the exception that ethyl acetate was used in place of ether The title compound (42 mg, 58 % yield) was obtained as a white solid Mp 221 °C dec 1 H NMR (400 MHz, CDCI 3 ) δ 1 15-1 25 (m, 1 H), 1 43-1 62 (m, 4H), 1 73 (br s, 1 H, J = 13 7 Hz), 1 82-1 90 (m, 4H), 2 41 (d, 3H, J = 0 8 Hz), 3 21 (s, 3H) 4 63 (br s, 1 H), 6 20 (s, 1 H), 8 22 (s, 1 H), 10 1 (br s, 1 H) LRMS 245 (M+1) The title compound of Example 88 were prepared by a method analogous to that described in Example 87 EXAMPLE 88 Cyclohexyl-(6-methyl-7H-pyrrolo[2,3-d]pyrirnidin-4-yl)-amine Cyclohexylamme LRMS 231 3 EXAMPLE 89 4-Cyclohexyloxy-7H-pyrrolo[2,3-d]pyrimidine METHOD L 7-Benzyl-4-chloro-7H-pyrrolo[2,3-d]pyrimidine To a stirred solution of 4-chloro-7H-pyrrolo[2,3-d]pyπmιdιne (250 mg/1 63 mmol) in 12 mL of DMF was added 676 mg (4 89 mmol) of potassium carbonate and the resulting mixture stirred at room temperature for 20 m Benzylchlonde (310 mg/2 45 mmol) was added and the new mixture stirred at room temperature for 24 h then filtered, concentrated and the residue purified by silica gel chromatography (3 1 hexanes/ethyl acetate) affording 318 mg (80%) of the title compound LRMS 244 1 (M+1) METHOD M 7-Benzyl-4-cyclohexyloxy-7H-pyrrolo[2,3-d]pyrimidine To a flame dried flask under nitrogen was charged 84 mg (2 10 mmol) of 60 % sodium hydride in mineral oil and 3 0 L of THF and the mixture cooled to 0 °C Cyclohexanol (0 18 mL/1 70 mmol) was added and the reaction mixture stirred for 5 mm A solution of 102 mg (0 419 mmol) of the product from Method L in 1 0 mL of THF was added and the mixture heated to reflux for 3 h After cooling to room temperature, the reaction mixture was acidified to pH 1 with 2 N HCI and concentrated in vacuo The resulting residue was then slurπed in ethyl acetate, filtered and the filtrate concentrated in vacuo to provide 76 mg (59%) of the title compound as an oil LRMS 308 (M+1) METHOD N 4-Cyclohexyloxy-7H-pyrrolo[2,3-d]pyrimidine To liquid ammonia (6 0 mL) at -78 °C was added 33 mg (1 43 mmol) sodium metal and the resulting dark blue solution stirred at -78 °C 10 mm A solution of 75 mg (0 244 mmol) of the product from Method M in 3 0 mL of ether was added dropwise over a 5 mm period The resulting solution stirred at -78 °C for 1 h followed by quenching upon addition of 500 mg of solid ammonium chloride After evaporation at room temperature, the residual solid was triturated with 25 mL of ethylacetate containing 1 mL of acetic acid for 1 h Filtration and concetration in vacuo afforded crude material which was purified by preparative thin layer chromatography (sihca-gel, 2 1 ethyl acetate/hexanes) to produce 5 mg of the title compound 1 H NMR (400 MHz) (CDCI 3 ) δ 1 27 - 1 35 (m, 6H), 1 62 - 1 67 (m, 4H), 5 30 - 5 36 (m, 1H), 6 55 (d, 1H, J = 3 2 Hz), 7 11 (d, 1H, J = 3 2 Hz), 8 37 (br s 1H) LRMS 218 2 (M+1) EXAMPLE 90 METHOD O 4-Cyclohexylsulfanyl-7H-pyrrolo[2,3-dlpyrimidine To a solution of 100 mg (0 651 mmol) of 4-chloro-7H-pyrrolo[2,3-d]pyπmιdιne dissolved in 3 0 mL of THF was added 0 10 mL (0 818 mmol) of cyclohexylmercaptan and 100 mg (0 847 mmol) of 95 % potassium tert-butoxide and the resulting mixture heated at reflux for 3 5 hr After cooling to room temperature, the reaction mixture was acidified to pH 1 with 2 N HCI and concentrated in vacuo The residue was then partitioned between ethylacetate and 1 N HCI The aqueous layer was extracted with ethyl acetate, the ethyl acetate layers were combined, washed with brine, dried over MgS0 4 , filtered, and evaporated in vacuo The cude product was purified by sihca-gel chromatography (1 3 ethylacetate/hexanes) providing 34 mg (22%) of the title compound as a white solid Mp 162-163 °C 1 H NMR (400 MHz) d 1 22-1 36 (m, 1H), 1 45-1 64 (m, 5H), 1 75-1 79 (m, 2H), 2 12-2 14 (m, 2H), 4 18-420 (m, 1H), 6 50 (d, 1H, J = 3 7 Hz), 7 19 (d, 1H, J = 3 5 Hz), 8 61 (s, 1H), 10 0 (br s, 1H) LRMS 234 (M+1) EXAMPLE 91 5-Chloro-4-piperidin-1-yl-7H-pyrrolo[2,3-d]pyrimidine METHOD R 4,5-Dichloro-7H-pyrrolo[2,3-d]pyrimidine 4-Chloro-7H-pyrrolo[2,3-d]pyrιmιdιne (154 mg, 1 0 mmol) was suspended in 6 0 mL of dry dichloromethane in a flame-dried flask and to this mixture was added N-chlorosuccinimide (147 mg, 1 1 mmol) in one portion The resulting mixture stirred at room temperature for 18 h, at which time the solvent was removed under reduced pressure The residue was triturated with water and isolated by filtration to afford 137 mg (72%) of the title compound as a gray solid, mp 224-227 °C(dec) LRMS 188 (M+1) METHOD S 5-Chloro-4-piperidin-1-yl-7H-pyrrolo[2,3-d]pyrimidine The product from Method R (57 mg, 0 3 mmol) was suspended in 3 0 mL of tert- butanol and to this solution was added pipeπdine (90μL, 0 9 mmol) and the resulting system heated at reflux for 1 h The reaction mixture was cooled to room temperature and water was added (4 0 mL) The solution was adjusted to pH 1 with 1 N HCI and then washed with ether The aqueous layer was removed and adjusted to pH 12 with 2 N NaOH The solution was then extracted 2 x 15 mL with dichloromethane and the combined organics washed with water then brine and dried over MgS0 4 Evaporation of solvent afforded 45 mg of a yellow solid that was punfied by sihca-gel chromatography (3 1 ethyl acetate/hexanes) to yield 23 mg (32%) of the title compound as a light yellow solid Mp 170 - 172 °C 1 H NMR (400 MHz, CDCI 3 ) δ 1 67 - 1 74 (m, 6H), 3 65 - 367 (m, 4H), 7 10 (s, 1H), 8 31 (s, 1H) LRMS 237 (M + 1) The title compounds of Examples 92-94 were prepared by a method analogous to that described in Example 91 EXAMPLE 92 (5-Chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-(3-ethynyl-phenyl)-amine 3-Ethynylphenyl)amιne Melting Point 250°C EXAMPLE 93 (5-Chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-cycloheptyl-methyl-amine Cycloheptylmethylamme Melting Point 152 - 153°C, LRMS 279 8 EXAMPLE 94 (5-Chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-cyclooctyl-methyl-amine Cycloooctylmethylamme Melting Point 151 - 153°C, LRMS 293 8 EXAMPLE 95 5-Phenyl-4-piperidin-1-yl-7H-pyrrolo[2,3-d]pyrimidine METHOD T 5-Bromo-4-chloro-7H-pyrrolo[2,3-d]pyrimidine To a stirred solution of 4-chloro-7H-pyrrolo[2,3-d]pyπrnιdιne (30 g/0 02 mol) dissolved in 75 mL of chloroform was added 3 5 g (0 02 mol) of N-bromosuccinamide and the resulting mixture refluxed for 1 h After cooling to room temperature, the precipitate was removed by filtration and dried under reduced pressure affording 4 1 g (89%) of the title compound 1 H NMR (400 MHz) (CDCI 3 ) δ 7 93 (d, 1 H, J = 2 8 Hz), 8 60 (s, 1 H) METHOD U 7-Benzenesulfonyl-5-bromo-4-chloro-7H-pyrrolo[2,3-d]pyrimidine To a slurry of the product from Method T (4 1 g/0 018 mol) in DMF (15 mL) and cooled to 0 °C was added 1 0 g (0 025 mol) of 60% sodium hydride in mineral oil and the resulting mixture stirred at 0 °C for 15 m Benzenesulfonyl chloride (3 2 g/0 018 mol) was added, the reaction mixture warmed to room temperature and stirred for 2 h Water was then added (15 mL) and the resulting solid removed by filtration and dried in vacuo affording 5 9 g (89%>) of the title compound METHOD V 7-Benzenesulfonyl-5-bromo-4-piperidin-1-yl-7H-pyrrolo[2,3-d]pyrimidine A mixture of 2 0 g (5 37 mmol) of the product from Method U and 1 1 g (134 mmol) of pipeπdine in 10 mL of te/τ-butanol was heated with stirring at 60 °C for 2 h After cooling to room temperature, the reaction mixture was partitioned between dichloromethane (25 mL) and water (25 mL) The dichloromethane layer was dried over sodium sulfate (Na 2 S0 4 ) and concentrated to dryness in vacuo affording 2 2 g (97%) of the title compound 1 H NMR (400 MHz) (CDCI 3 ) δ 1 63 - 1 72 (m, 6H), 3 54 - 3 57 (m, 4H), 7 53 (t, 2H, J = 2 0 Hz), 7 60 (s, 1 H) 7 61 (t, 1H, J = 2 0 Hz), 8 17 - 8 20 (m, 2H), 8 43 (s, 1 H) LRMS 422 7, 420 7 (M+1 ) METHOD W 5-Phenyl-4-piperidin-1-yl-7H-pyrrolo[2,3-d]pyrimidine To a stirred solution of the product from Method V (100 mg/0 237 mmol) in 1 0 mL of dioxane was added 32 mg (0 261 mmol) of phenylboronic acid and 75 mg (0 356 mmol) of tπbasic potassium phosphate followed by 7 mg (0 006 mmol) of tetrakιs(tπphenylphosphιne) palladium The resulting mixture was degassed with nitrogen and stirred at 100 °C for 48 h After cooling to room temperature, 1 0 mL of methanol was added followed by 50 mg of NaOH and the new mixture stirred at room temperature for 1 h The resulting mixture was then partitioned between dichloromethane and water, the dichloromethane layer dried over MgS0 4 and concentrated to dryness in vacuo The crude product was purified by sihca-gel chromatography (2 1 ethyl acetate/hexanes) affording 13 mg ( 20%) of the title compound 1 H NMR (400 MHz) (CDCI 3 ) δ 1 33 - 1 34 (m, 4H), 1 43 - 1 44 (m, 2H), 3 26 - 3 28 (m, 4H), 7.12 (s, 1H), 7.27 (t, 1 H, J = 7.2 Hz), 7.38 (t, 2H, J = 8.0 Hz), 7.45 (d, 2H, J = 0.8 Hz), 8.42 (s, 1 H). LRMS:279.2 (M+1). The title compounds of Examples 96-99 were prepared by a method analogous to that described in Example 95. EXAMPLE 96 Cyclohexyl-methyl-(5-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Cyclohexylmethylamine. Melting Point: 200°C; LRMS: 307.4. EXAMPLE 97 Cyclohexyl-[5-(4-fluoro-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-methyl-amine Cyclohexylmethylamine. Melting Point: 220°C; LRMS: 325.4. EXAMPLE 98 Bicyclo[2.2.1]hept-2-yl-(5-phenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amine Bicyclo[2.2.1]hept-2-yl-amine. LRMS: 305.4. EXAMPLE 99 [5-(3-Chloro-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-cyclohexyl-methyl-amine Cyclohexyl-methylamine. LRMS: 455.9. EXAMPLE 100 METHOD X 4-Piperidin-1-yl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile To a stirred solution of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile (54 mg/0.3 mmol) (prepared by the method of Townsend, et. al., J. Am. Chem. Soc, 1969, 9J, 2102) suspended in 3.0 mL tert-Butanol was added piperidine (59 μL/0.60 mmol). The resulting mixture was then heated at reflux for 2.5 h and after cooling to room temperature, was transferred to a separatory funnel and diluted with ether (20 mL). The solution was extracted 2 x 10 mL with 1N HCI, the combined aqueous layers were adjusted to pH 7 with 2 N potassium hydroxide (KOH) solution forming a precipitate which was collected by filtration, washed with water and dried under reduced pressure to give 29 mg (42%) of the title compound as a colorless solid. Mp 209 - 211 °C; 1 H NMR (400 MHz) (acetone-d6) δ: 1.72 - 1.74 (m, 6H), 3.72 - 3.79 (m, 4H), 8.12 (s, 1H), 8.29 (s, 1H). LRMS: 228 (M + 1). EXAMPLE 101 5-Ethynyl-4-piperidin-1-yl-7H-pyrrolo[2,3-d]pyrimidine METHOD Y 4-Chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine To a stirred solution of 4-chloro-7H-pyrrolo[2,3-d]pyπmιdιne (30 g/0 02 mol) dissolved in 80 mL of chloroform was added 4 5 g (0 02 mol) of N-iodosucciπimide and the resulting mixture heated at reflux for 1 h After cooling to room temperature, the percipitate was removed by filtration and dried under reduced pressure affording 4 6 g (82%) of the title compound METHOD Z 7-Benzenesulfonyl-4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidine The title compound was prepared as previously described in Method U using the product from Method X affording 54 g (80%) of material LRMS 419 6 (M+1 ), 279 7 METHOD AA 7-Benzenesulfonyl-5-iodo-4-piperidin-1-yl-7H-pyrrolo[2,3-d]pyrimidine The title compound was prepared by the procedure described in Method V using the product from Method Z to produce the title compound LRMS 469 (M+1), 329 1 METHOD BB 7-Benzenesulfonyl-4-piperidin-1-yl-5-triethylsilanylethynyl-7H-pyrrolo[2,3- djpyrimidine To a flamed-dπed flask under nitrogen was charged 211 mg (0 5 mmol) of the product from Method AA, 19 mg (0 1 mmol) of copper (I) iodide and 58 mg (0 05 mmol) of tetrakιs(tπphenylphosphιne)palladιum To this mixture was then added 0 14 mL (1 0 mmol) of tπethylamine and 027 mL (1 5 mmol) of tπethylsilylacetylene as a solution in 1 5 mL of dry DMF The resulting mixture stirred at room temperature for 3 h, at which time, 5 0 mL of water were added and the mixture extracted with ethylacetate The ethyl acetate extract was dried over MgS0 4 and concentrated in vacuo The resulting crude product was then purified by si ca-gel chromatography (7 1 hexanes/ethyl acetate) affording 194 mg (89%) of the title compound LRMS 481 (M+1 ), 341 METHOD CC 5-Ethynyl-4-piperidin-1-yl-7H-pyrrolo[2,3-d]pyrimidine To a stirred solution of the product from Method BB (194 mg/040 mmol) dissolved in 2 0 mL of dry THF was added dropwise 0 4 mL (0 4 mmol) of a 1 M solution of tetrabutylammonium fluoride in THF The resulting mixture stirred at room temperature for 10 mm, then was transferred to a methanol solution (3 0 mL) containing 1 g of KOH, the new mixture stirred at room temperature for 15 mm and concentrated in vacuo The residue was partitioned between water and ethyl acetate, the ethyl acetate layer washed with water and brine, dried over MgS0 4 and concentrated to dryness in vacuo The crude product was purified by sihca-gel chromatography (21 ethyl acetate/hexanes) affording 72 mg (64%) of the title compound as a white crystalline solid Mp 179 - 181 °C 1 H NMR (400 MHz) (CDCI 3 ) d 172 (br s, 6H), 320 (s, 1H), 382 - 383 (m, 4H), 747 (s, 1H), 835 (s, 1H) LRMS 227 (M+1)

Claims: CLAIMS A compound of the formula or the pharmaceutically acceptable salt thereof, wherein R 1 is a group of the formula wherein y is 0, 1 or 2, R 4 ιs selected from the group consisting of hydrogen, (C,-C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 - C 6 )alkynyl wherein the alkyl, alkenyl and alkynyl groups are optionally substituted by deuterium, hydroxy, ammo, tnfluoromethyl, (C 1 -C 4 )alkoxy, (C 1 -C 6 )acyloxy, (CrC-Jalkylamino, cyano, nitro, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl or (C 1 -C 6 )acylamιno, or R 4 is (C 3 -C 10 )cycloalkyl wherein the cycloalkyl group is optionally substituted by deuterium, hydroxy, ammo, tnfluoromethyl, (C r C 6 )acyloxy, (C^CsJacylammo, (CrC^alkylammo, ((C r C 6 )alkyl) 2 amιno, cyano, cyano(C 1 -C 6 )alkyl, trιfluoromethyl(C 1 -C 6 )alkyl, nitro, nιtro(C 1 -C 6 )alkyl R 5 is selected from the group consisting of tπfluoromethyl(C 1 -C 6 )alkyl, (C r C 3 )alkyl(dιfluoromethylene)(C 1 -C 3 )alkyl, (C 3 -C 10 )cycloalkyl wherein the cycloalkyl group is optionally substituted by one to five carboxy, cyano, ammo, deuterium, hydroxy, (C 1 -C 6 )alkyl, (C 1 -C β )alkoxy, halo, (C,-C 6 )acyl, (C 1 -C 6 )alkylamιno, amιno(C 1 -C 6 )alkyl, (C C^alkoxy-CO-NH, (C CeJalkylamino-CO-, (C 2 -C 6 )alkenyl, (C 2 -C 6 ) alkynyl, amιno(C 1 -C 6 )alkyl, hydroxy(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C 1 -C 6 )acyloxy(C 1 -C 6 )alkyl, nitro, cyano(C 1 - C 6 )alkyl, halo(C 1 -C 6 )alkyl, nιtro(C 1 -C 6 )alkyl, tnfluoromethyl, tπfluoromethy CrC^alkyl, (C C 6 )acylamιno, (C 1 -C 6 )acylamιno(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy(C 1 -C 6 )acylamιno, amιno(C 1 - C 6 )acyl, amιno(C l -C 6 )acyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylamιno(C 1 -C 6 )acyl, ((C 1 -C 6 )alkyl) 2 amιno(C 1 - C 6 )acyl, R 15 R 16 N-CO-0-, R 15 R 16 N-CO-(C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl-S(0) m , R 15 R 16 NS(0) m , R 15 R 16 NS(0) m (C r C 6 )alkyl, R 15 S(0) m R 16 N, R 15 S(0) m R 16 N(C r C 6 )alkyl wherein m is 0, 1 or 2 and R 15 and R 16 are each independently selected from hydrogen or (C.,-C 6 )alkyl, or R 5 is (C 3 - (C 1 -C 6 )acyloxy(C 1 -C 6 )alkyl, (C 2 -C 6 )alkoxy(C 1 -C 6 )alkyl, pιperazιnyl(C r C 6 )alkyl, (C 1 -C 6 )acylamιno(C 1 -C 6 )alkyl, (Cg-C ary C C^alkoxyfC CeJalkyl, (C 5 -C 9 )heteroaryl(C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylthιo(C 1 -C 6 )alkyl, C 6 )alkyl, (C 1 -C 6 )alkylsulfinyl(C 1 -C 6 )alkyl, (C CβJalkylsulfony CrCeJalkyl, (C 6 -C 10 )arylsulfonyl(C r C 6 )alkyl, amιno(C 1 -C 6 )alkyl, (C r C 6 )alkylamιno(C 1 -C 6 )alkyl, ((C r C 6 )alkyl) 2 amιno, (C r C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl wherein the alkyl, alkenyl and alkynyl groups are optionally substituted by one to five cyano, nitro, halo, deuterium, hydroxy, carboxy, (C 1 -C 6 )alkoxy(C 1 -C 6 )acylamιno, amιno(C 1 -C 6 )acyl, (C 1 -C 6 )alkylamιno(C 1 -C 6 )acyl or ((C 1 -C 6 )alkyl) 2 amιno(C 1 -C 6 )acyi, or R 5 is R 13 CO(C 1 -C 6 )alkyl or R 3 CO(C 3 -C 10 )cycloalkyl wherein R 13 is R 20 O or R 20 R 21 N wherein R 20 and R 21 are each independently selected from the group consisting of hydrogen, deuterium, (C r C 6 )alkyl, (Ce-C ary C CeJalkyl or (Cs-CgJheteroaryKC.-CeJalkyl, or R 5 is R 14 , R^-OOalkyl or R 1 (C 3 -C 10 )cycloalkyl wherein R 14 is (C 2 -C 9 )heterocycloalkyl, (C 1 -C 6 )acylpιperazιno, (C 6 - C 10 )arylpιperazιno, (C 6 -C 9 )heteroarylpιperazιno, (C 1 -C 6 )alkylpιperazιno, (C 6 -C 10 )aryl(C. | - C 6 )alkylpιperazιno, (C 5 -C 9 )heteroaryl(C 1 -C 6 )alkylpιperazιno, morpholino, thiomorpholino, piperidmo, pyrrolidino, piperidyl, (C C^alkylpipeπdinyl, (C 6 -C 10 )arylpιpeπdyl, (C 5 - C 9 )heteroarylpιperιdyl, (Ce-C^Jary C CgJalkylpipeπdyl, (C 5 -C 9 )heteroaryl(C 1 -C 6 )alkylpiperidyl or (C 1 -C 6 )acylpιperιdyl, or R 5 is a group of the formula wherein w is 0, 1 or 2, x is 0, 1 , 2 or 3, or R 5 is a group of the formula wherein g, h and j are each independently 0 to 3, F, K and P are each independently oxygen, S(0) d wherein d is 0, 1 or 2, NR 6 or CR 7 R 8 , R 6 is selected from the group consisting of hydrogen, (C r C 6 )alkyl, tnfluoromethyl, trifluoromethy CTCgJalkyl, (C 1 -C 6 )alkyl (difluoromethylene), (C 1 -C 3 )alkyl(dιfluoromethylene)(C 1 - C 3 )alkyl, (C 1 -C 6 )alkoxy(C 1 -C 6 )acyl, (C 1 -C 6 )alkylamιno(C 1 -C 6 )acyl, ((C 1 -C 6 )alkyl) 2 amιno(C 1 - C 6 )acyl, (C 6 -C 10 )aryl, (C 5 -C 9 )heteroaryl, (C 6 -C 9 )heteroaryl(C 1 -C 6 )alkyl, (C 6 -C 10 )aryl(C 6 -C 10 )aryl, (C 6 -C 1 o)aryl(C 6 -C 10 )aryl(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 3 - CeJcycloalky C CeJalkyl, hydroxy(C 2 -C 6 )alkyl, (C 1 -C 6 )acyloxy(C 2 -C 6 )alkyl, (C 1 -C 6 )alkoxy(C 2 - C 6 )alkyl, (C r C 6 )acylamino(C r C 6 )alkyl, (C 6 -C 10 )aryl(C 1 -C 6 )alkoxy(C 1 - C 6 )alkyl, (C 5 -C 9 )heteroaryl(C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylthιo(C 1 -C 6 )alkyl, (C 6 - C 10 )arylthιo(C r C 6 )alkyl, (CrC^alkylsulfiny CrCeJalk l, (C 6 -C 10 )arylsulfinyl(C r C 6 )alkyl, (C r C 6 )alkylsulfonyl(C C 6 )alkyl, (Ce-C arylsulfony CrC^alkyl, amιno(C 1 -C 6 )alkyl, (C r C 6 )alkylamιno(C 1 -C 6 )alkyl, ((C 1 -C 6 )alkyl) 2 amιno(C 1 -C 6 )alkyl, R 13 CO(C 1 -C 6 )alkyl wherein R 13 is R 0 O or R 20 R 21 N wherein R 20 and R 21 are each independently selected from the group consisting of hydrogen, (C r C 6 )alkyl, (Cs-C ary CrCsJalkyl or (C 5 -C 9 )heteroaryl(C 1 -C 6 )alkyl, or R 14 (C 2 - C 6 )alkyl wherein R 14 is (C 1 -C 6 )acylpιperazιno, (C 6 -C 10 )arylpιperazιno, (C 5 - C 9 )heteroarylpiperazino, (C 1 -C 6 )alkylpιperazιno, (C 6 -C 10 )ai7l(C r C 6 )alkylpιperazιno, (C 5 - CgJheteroary C^CeJalkylpiperazmo, morpholino, thiomorpholino, piperidmo, pyrrolidino, piperidyl, (C 6 -C 10 )arylpιpeπdyl, (C 5 -C 9 )heteroarylpiperidyl, (Cg-C ary C,- C 6 )alkylpιpeπdyl, (C 3 -C 9 )heteroaryl(C 1 -C 6 )alkylpιpeπdyl, (C r C 6 )alkoxyacyl, (CrCsJalkylaminoaryl, ((C 1 -C 6 )alkyl 2 amιnoacyl or (C 1 -C 6 )acylpιpeπdyl, R 7 and R 8 are each independently selected from the group consisting of hydrogen, (C,- C 6 )alkyl, ammo, hydroxy, (C C 6 )alkoxy, (C r C 6 )alkylamιno, ((C 1 -C 6 )alkyl)amιno, (C,- C 6 )acylamιno, (C 1 -C 6 )acyl(C 1 -C 6 )alkylamιno, carboxy, (CrC^alkoxyacyl, (C 1 -C 6 )alkylamιnoacyl, ((C 1 -C 6 )alkyl) 2 amιnoacyl, aminoacyl, tnfluoromethyl, (difluoromethylene), (C 1 -C 3 )alkyl(dιfluoromethylene)(C 1 -C 3 )alkyl, (C 6 -C 10 )aryl, (C 5 -C 9 )heteroaryl, (Ce-C^Jary C C^alkyl, (Cs-C^heteroaryKC^alkyl, (C 6 -C 10 )aryl(C 6 -C 10 )aryl, (C 6 -C 10 )aryl(C 6 - C 10 )aryl(C r C 6 )alkyl, (C 3 -C 6 )cycloalkyl, hydroxy(C 1 -C 6 )alkyl, (C,- C 6 )acyloxy(C r C 6 )alkyl, (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C 1 -C β )acylamιno(C 1 - C 6 )alkyl, piperidyl, (C 6 -C 10 )aryl(C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C 5 - C 9 )heteroaryl(C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylthιo(C 1 -C 6 )alkyl, (C 6 -C 10 )arylthιo(C 1 -C 6 )alkyl, (C CsJalkylsulfiny C^CgJalkyl, (C 6 -C 10 )arylsulfinyl(C r C 6 )alkyl, (C C^alkylsulfony CrC^alkyl, (C 6 -C 10 )arylsulfonyl(C r C 6 )alkyl, amιno(C r C 6 )alkyl, (C 1 -C 6 )alkylamιno(C 1 -C 6 )alkyl, ((C r C 6 )alkyl) 2 amιno(C 1 -C 6 )alkyl, R 13 CO(C 1 -C 5 )alkyl or R 13 CO(C 3 -C 10 )cycloalkyl wherein R 13 is R 20 O or R 20 R 21 N wherein R 20 and R 21 are each independently selected from the group consisting of hydrogen, (C r C 6 )alkyl, R 14 , R 1 (C r C 6 )alkyl or R 14 (C 3 -C 10 )cycloalkyl wherein R 14 is (C r C 6 )acylpiperazino, (C 6 -C 10 )arylpιperazιno, (C 5 -C 9 )heteroarylpιperazιno, (C r C 6 )alkylpιperazιno, (C 6 -C 10 )aryl(C 1 -C 6 )alkylpιperazιno, (C 5 - C 9 )heteroaryl(C 1 -C 6 )alkylpιperazιno, morpholino, thiomorpholino, piperidmo, pyrrolidino, pipendyl, (C 6 -C 10 )arylpιpeπdyl, (C 6 -C 9 )heteroarylpιpeπdyl, (C 6 -C 10 )aryl(C r Cg)alkylpιpeπdyl, (Cs-CgJheteroary C CgJalkylpipendyl or (C r C 6 )acylpiperidyl, or a group of the formula wherein p is 0, 1, 2 or 3, and Z is hydroxy, (C C 6 )alkoxy or NR 1 R 2 wherein R 1 and R 2 are each independently selected from the group consisting of hydrogen, (C 1 -C 6 )alkyl, pipendyl, (C r C 6 )alkylpιpeπdyl, (C 6 - C 10 )arylpιpeπdyl, (C 5 -C 9 )heteroar7lpiperidyl, (C 6 -C 10 )aryl(C 1 -C 6 )alkylpιpeπdyl, (C 5 - C 9 )heteroaryl(C 1 -C 6 )alkyipiperidyl, (C 1 -Cg)acylpιpeπdyl, (C 6 -C 10 )aryl, (C 5 -C 9 )heteroaryl, (C 6 - C 10 )aryl(C r C 6 )alkyl, (C 5 -C 9 )heteroaryl(C 1 -C 6 )alkyl, (C 6 -C 10 )aryl(C 6 -C 10 )aryl, (C 6 -C 10 )aryl(C 6 - C 10 )aryl(C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl(C 1 -C 6 )alkyl, R 5 (C r C 6 )alkyl, (C r C s )alkyl(CHR 5 )(C 1 -C 6 )alkyl wherein R 6 is hydroxy, (C^acyloxy, (C r C 6 )alkoxy, piperazmo, (C r C 6 )acylamιno, (C r C 6 )alkylthιo, (C 6 -C 10 )arylthιo, (CrCgJalkylsulfinyl, (C e -C 10 )arylsulfinyl, (C r C 6 )alkylsulfoxyl, (C 6 -C 10 )arylsulfoxyl, ammo, (C 1 -C β )alkylamιno, ((C r C 6 )alkyl) 2 ammo, (C r C 6 )acylpιperazιno, (C 1 -C 6 )alkylpιperazιno, (C 6 -C 10 )aryl(C 1 -C 6 )alkylpιperazιno, (C 5 - C 9 )heteroaryl(C 1 -C β )alkylpιperazιno, morpholino, thiomorpholino, piperidmo or pyrrolidino, R 6 (C r C 6 )alkyl, (C 1 -C 5 )alkyl(CHR 6 )(C 1 -C 6 )alkyl wherein R 6 is pipendyl, (C r C 6 )alkylpιpeπdyl, (C 6 - C 10 )arylpιperιdyl, (C 6 -C 10 )aryl(C 1 -C 6 )alkylpιpeπdyl, (C 5 -C 9 )heteroarylpιpeπdyl or (C 5 - C 9 )heteroaryl(C 1 -C 6 )alkylpiperidyl, or R 1 is defined as OR 9 or S(0) q R 9 wherein q is 0, 1 or 2, and R 9 is selected from the group consisting of tπfluoromethy C C^alkyl, (C,- C 3 )alkyl(dιfluoromethylene)(C 1 -C 3 )alkyl, (C 3 -C 10 )cycloalkyl wherein the cycloalkyl group is optionally substituted by one to five carboxy, cyano, ammo, hydroxy, (CrCg) alkoxy, halo, (C,- C 6 )alkyl S(0) m wherein m is 0, 1 or 2, R 15 R 16 NS(0) m wherein m is 0, 1 or 2 and R 15 and R 16 are each independently selected from hydrogen or (C CgJal yl, (C r C 6 )acyl, (C 1 -C 6 )alkylamιno, amιno(C 1 -C 6 )alkyl, (C r C 6 )alkoxy-CO-NH, (C 1 -C 6 )alkylamιno-CO-, R 15 R 16 N-0O-O-, R 15 R 16 N- herein R 15 and R 16 are as defined above, (C 2 -C 6 )alkenyl, (C 2 -C 6 ) alkynyl, amιno(C 1 -C 6 )alkyl, hydroxy(C r C 6 )alkyl, (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C r C 6 )acyloxy(C 1 -C 6 )alkyl, nitro, cyano(C 1 -C 6 )alkyl, nιtro(C r C 6 )alkyl, tnfluoromethyl, tπfluoromethyl(C 1 -Cg)alkyl, (CrCgJacylammo, (C 1 -C 6 )alkoxy(C 1 -C 6 )acylamιno, amιno(C r C 6 )acyl, (C 1 -C 6 )alkylamιno(C 1 -C 6 )acyl or ((C 1 -C 6 )alkyl) 2 amιno(C 1 -C 6 )acyl, (C 2 -C 6 )alkenyl, (C 2 - C 6 )alkynyl, (C 3 -C 10 )cycloalkyl(C r C 6 )alkyl, (C 1 -C 6 )acyloxy(C 1 -C 6 )alkyl, (C 2 -C 6 )alkoxy(C r C 6 )alkyl, piperazmy C CgJalkyl, (C 1 -C 6 )acylamιno(C 1 -C 6 )alkyl, (C 6 -C 10 )aryl(C 1 -C 6 )alkoxy(C 1 - C 6 )alkyl, (C 5 -C 9 )heteroaryl(C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl, (C 1 -C 6 )alkylthιo(C 1 -C 6 )alkyl, (C 6 - C 10 )arylthio(C 1 -C 6 )alkyl, (C CgJalkylsulfmy CrCgJalk l, (C 6 -C 10 )arylsulfιnyl(C l -C 6 )alkyl, (C,- C 6 )alkylsulfonyl(C r C 6 )alkyl, amιno(C 1 -C 6 )alkyl, (C r C 6 )alkylamιno(C 1 -C 6 )alkyl, ((C r C 6 )alkyl) 2 amιno, (C r C 6 )alkyl wherein the alkyl group is optionally substituted by one to five cyano, nitro, hydroxy, carboxy, (C,- C 6 )alkoxy(C 1 -C 6 )acylamιno, amιno(C 1 -C 6 )acyl, (C 1 -C 6 )alkylamιno(C 1 -C 6 )acyl or ((C R 13 CO(C 1 -C 6 )alkyl or R 13 CO(C 3 -C 10 )cycloalkyl wherein R 13 is R 20 O or R 20 R 21 N wherein R 20 and R 21 are each independently selected from the group consisting of hydrogen, (C CgJalkyl, R 14 , R 14 (C C 6 )alkyl or R 1 (C 3 -C 10 )cycloalkyl wherein R 14 is (C 2 -C 9 )heterocycloalkyl, (CrCgJacylpiperazmo, (C 6 -C 10 )arylpιperazιno, (C 5 -C 9 )heteroarylpιperazιno, C 6 )alkylpiperazino, (C 5 -C 9 )heteroaryl(C 1 -C 6 )alkylpιperazιno, morpholino, thiomorpholino, piperidmo, pyrrolidino, pipendyl, (C 1 -C 6 )alkylpιpeπdιnyl, (C 6 -C 10 )arylpιpeπdyl, (C 5 - C 9 )heteroarylpιpeπdyl, (C 5 -C 9 )heteroaryl(C 1 -C 6 )alkylpiperidyl or (C 1 -C 6 )acylpiperidyl, or R 9 is a group of the formula wherein g, h and j are each independently 0 to 6, F, K and P are each independently oxygen, S(0) d wherein d is 0, 1 or 2, NR 6 or CR 7 R 8 wherein R 6 , R 7 and R 8 are as defined above, R 2 and R 3 are each independently selected from the group consisting of hydrogen, deuterium, ammo, halo, hydoxy, nitro, carboxy, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, tnfluoromethyl, tπfluoromethoxy, (C 1 -C 6 )alkyl, (C r C 6 )alkoxy wherein the alkyl or alkoxy groups are optionally substittued by one to three groups selected from halo, hydroxy, carboxy, ammo (C r C 6 )alkylthιo, (C.|-C 6 )alkylamιno, ((C 1 -C 6 )alkyl) 2 amιno, (C 5 -C 9 )heteroaryl, (C 2 - C 9 )heterocycloalkyl, (C 3 -C 9 )cycloalkyl or (C 6 -C 10 )aryl, or R 2 and R 3 are each independently (C 3 -C 10 )cycloalkyl, (C 3 -C 10 )cycloalkoxy, (C r C 6 )alkylamιno, ((C 1 -C 6 )alkyl) 2 amιno, (C 6 - C 10 )arylamιno, (C r C 6 )alkylthιo, (C 6 -C 10 )arylthιo, (C CeJalkylsulfmyl, (C 6 -C 10 )arylsulfιnyl, (C,- C 6 )alkylsulfonyl, (C 6 -C 10 )arylsulfonyl, (C 1 -C 6 )acyl, (CrCgJalkoxy-CO-NH-, (C C^alkyamino- CO-, (C 5 -C 9 )heteroaryl, (C 2 -C 9 )heterocycloalkyl or (C 6 -C 10 )aryl wherein the heteroaryl, heterocycloalkyl and aryl groups are optionally substituted by one to three halo, (C r C 6 )alkyl, (C C alkyl-CO-NH-, (C 1 -Cg)alkoxy-CO-NH-, (C^CβJalkyl-CO-NH-fCrCβJalkyl, (C r C β )alkoxy- (C 1 -C 6 )alkoxy-CO-NH-(C 1 -C 6 )alkoxy, carboxy, carboxy(C r C 6 )alkyl, carboxy(C 1 -C 6 )alkoxy, benzyloxycarbony C CgJalkoxy, (C 1 -C 6 )alkoxycarbonyl(C 1 -C 6 )alkoxy, (C 6 -C 10 )aryl, ammo, amιno(C 1 -C 6 )alkyl, (CrCgJalkoxycarbonylamino, C 6 )alkoxycarbonylamιno, (C 1 -C 6 )alkylamιno, ((C 1 -C 6 )alkyl) 2 amιno, (C 1 -C 6 )alkylamιno(C 1 - C 6 )alkyl, ((C 1 -C 6 )alkyl) 2 amιno(C 1 -C 6 )alkyl, hydroxy, (C,-C 6 )alkoxy, carboxy, carboxy(C r C 6 )alkyl, (C 1 -C 6 )alkoxycarbonyl, (C 1 -C 6 )alkoxycarbonyl(C 1 -C 6 )alkyl, (C r C 6 )alkoxy-CO-NH-, (C CgJalkyl-CO-NH-, cyano, (C 3 -C 9 )heterocycloalkyl, ammo-CO-NH-, (C 1 -C 6 )alkylamιno-CO- NH-, ((C 1 -C 6 )alkyl) 2 amιno-CO-NH-, (C 6 -C 10 )aιylamιno-CO-NH-, (C 5 -C 9 )heteroarylamιno-CO- NH-, (C 1 -C 6 )alkylamιno-CO-NH-(C 1 -C 6 )alkyl, ((C 1 -C 6 )alkyl) 2 amιno-CO-NH-(C 1 -C 6 )alkyl, (C 6 - C 10 )arylamιno-CO-NH-(C 1 -C 6 )alkyl, (C 3 -C 9 )heteroarylamιno-CO-NH-(C 1 -C 6 )alkyl, (C,- C 6 )alkylsulfonyl, (C 1 -C 6 )alkylsulfonylamιno, (C 1 -C 6 )alkylsulfonylamιno(C 1 -C 6 )alkyl, (C 6 - C 10 )arylsulfonyl, (C 6 -C 10 )arylsulfonylamιno, (C 6 -C 10 )arylsulfonylamιno(C 1 -C 6 )alkyl, (C,- Cg)alkylsulfonylamιno, (C 1 -C 6 )alkylsulfonylamιno(C 1 -C 6 )alkyl, (C 5 -C 9 )heteroaryl or (C 2 - C 9 )heterocycloalkyl, with the proviso that when either R 4 and R 5 is hydrogen, the other of R 4 or R 5 cannot be (C 6 -C 10 )aryl or (C β -C 10 )aryl(C r C β )alkyl, with the proviso that when R 4 is hydrogen, unsubstituted (C r C 6 )alkyl or unsubstituted (C 3 -C 10 )cycloalkyl, R 5 cannot be R 20 and R 21 cannot be (C 5 - C 9 )heteroaryl(C 1 -C 6 )alkyl, and R 14 cannot be (C 2 -C 9 )heterocycloalkyl, morpholino, thiomorphlmo, piperidmo, pyrrolidino, pipeπdinyl or (C 1 -C 6 )alkylpιperιdιnyl, with the proviso that the sp 2 and sp carbons of alkenyl or alkynyl cannot be substituted by hydroxy or ammo, with the proviso that when R 4 is hydrogen, R 5 cannot be am o (C 1 -C 6 )alkyl, (C C 6 )alkyl, (C 1 -C 6 )alkylamιno(C 1 -C β )alkyl, ((C 1 -C 6 )alkyl) 2 amιno(C 1 -C 6 )alkyl, furanyl, (C,- C 6 )alkoxy(C 1 -C 6 )alkyl or carboxy(C 1 -C 6 )alkyl, with the proviso that both R 4 and R 5 cannot both be hydroxy (C^C^alkyl, with the proviso that when R 4 is (C^C^alkyl, R 5 cannot be (C 1 -C 6 )alkoxy(C 1 -C 6 )alkyl or carboxy(C 1 -C 6 )alkyl, and with the proviso that R 1 cannot be carboxy(C,-C 6 )alkylthιo or (C,- C^alkoxycarbony C^CgJalkylthio 2 A compound according to claim 1 , wherein R 1 is NR 4 R 5 3 A compound according to claim 1 , wherein R 4 is hydrogen, (C 2 - C 6 )alkenyl, (C 2 -C 6 )alkynyl wherein the alkyl, alkenyl and alkynyl groups are optionally substituted by hydroxy, ammo, tnfluoromethyl, (C CgJacyloxy, (C r C 6 )alkylamιno, ((C r Cg)alkyl) 2 amιno or (C 1 -C 6 )acylamιno, or R 4 is (C 3 -C 10 )cycloalkyl wherein the cycloalkyl group is optionally substituted by hydroxy, tnfluoromethyl or (C 1 -C 6 )acyloxy 4 A compound according to claim 1 , wherein R 5 is (C 3 -C 10 )cycloalkyl wherein the cycloalkyl group is optionally substituted by one to five deuterium, hydroxy, tnfluoromethyl, halo, (C r C 6 )alkyl, hydroxy(C r C 6 )alkyl, (C r C 6 )acyl, (C 1 -C 6 )alkylamιno(C 1 -C 6 )acyl, ((C r C 6 )alkyl) 2 amιno(C 1 -C 6 )acyl, (C CgJacylammo, (C 1 -C 6 )alkoxy-CO-NH, (C 1 -C 6 )alkylamιno-CO-, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, halo(C r C 6 )alkyl, (C 1 -C 6 )acylamιno(C 1 -C 6 )alkyl, R 15 S(0) m R 16 N, R 15 S(0) m R 16 N(C r C 6 )alkyl wherein m is 0, 1 or 2 and R 15 and R 16 are each independently selected from hydrogen or 5 A compound according to claim 1 , wherein R 2 and R 3 are each independently selected from the group consisting of hydrogen, halo, (C r C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 - C β )alkynyl, (C r C 6 )alkoxy, (C 3 -C 10 )cycloalkyl, (C 3 -C 10 )cycloalkoxy, (C 2 -C 9 )heterocycloalkyl, (C 5 - C 9 )heteroaryl or (C 6 -C 10 )aryl 6 A compound according to claim 1 , wherein said compound is selected from the group consisting of 2-{4-Methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyπmιdιn-4-yl)-amιno]-cyclohexyl}-propan-2- ol, 2-{3-[(2-Hydroxy-ethyl)-(7H-pyrrolo[2,3-d]pyπmιdιn-4-yl)-amιno]-4-methyl-cyclohexyl}- propan-2-ol, 2-[(5-lsopropenyl-2-methyl-cyclohexyl)-(7H-pyrrolo[2,3-d]pyπmιdm-4-yl)-amιno]- ethanol, (5-lsopropenyl-2-methyl-cyclohexyl)-(7H-pyrrolo[2,3-d]pyπmιdιn-4-yl)-(2,2,2-tπfluoro- ethyl)-amιne, 2-{4-Methyl-3-[(7H-pyrrolo[2,3-d]pyπmιdιn-4-yl)-(2,2,2-tπfluoro-ethyl)-amιno]- cyclohexyl}-propan-2-ol, 2-{4-Methyl-5-[methyl-(7H-pyrrolo[2,3-d]pyπmιdιn-4-yl)-amιno]-cyclohex-3-enyl}- propan-2-ol, 2-[1-(7H-Pyrrolo[2,3-d]pyπmιdιn-4-yl)-azetιdιn-3-yl]-propan-2-ol, 2-[1-(7H-Pyrrolo[2,3-d]pyπmιdιn-4-yl)-azetιdιn-2-yl]-propan-2-ol, (5-Fluoro-7H-pyrrolo[2,3-d]pyπmιdιn-4-yl)-(5-ιsopropenyl-2-methyl-cyclohexyl)-methyl- amme, 2-{3-[(5-Fluoro-7H-pyrrolo[2,3-d]pyπmιdιn-4-yl)-methyl-amιno]-4-methyl-cyclohexyl}- propan-2-ol, (2-Ethyl-4-ιsopropenyl-cyclopentyl)-methyl-(7H-pyrrolo[2,3-d]pyπmιdιn-4-yl)-amιne, 2-{3-Ethyl-4-[methyl-(7H-pyrrolo[2,3-d]pyπmιdιn-4-yl)-amιno]-cyclopentyl}-propan-2-ol, 2-{3-Ethyl-4-[(2-hydroxy-ethyl)-(7H-pyrrolo[2,3-d]pyπmιdιn-4-yl)-amιno]-cyclopentyl}- propan-2-ol, 2-[(2-Ethyl-4-ιsopropenyl-cyclopentyl)-(7H-pyrrolo[2,3-d]pyπmιdιn-4-yl)-amιno]- ethanol, (5-(S)-lsopropenyl-2-methyl-cyclohexyl)-methyl-(7H-pyrrolo[2,3-d]pyπmιdιn-4-yl)- amine, 3-Methyl-8-(7H-pyrrolo[2,3-d]pyπmιdιn-4-yl)-8-aza-bιcyclo[3 2 1]octan-3-ol, 2-[Cycloheptyl-(7H-pyrrolo[2,3-d]pyπmιdιn-4-yl)-amιno]-ethanol, 2-[Cyclooctyl-(7H-pyrrolo[2,3-d]pyπmιdιn-4-yl)-amιno]-ethanol, Bιcyclo[2 2 1]hept-2-yl-methyl-(7H-pyrrolo[2,3-d]pyπmιdιn-4-yl)-amιne, and 4-Pιpeπdιn-1-yl-5-m-tolyl-7H-pyrrolo[2,3-d]pyπmιdιne 7 A pharmaceutical composition for (a) treating or preventing a disorder or condition selected from organ transplant rejection, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, leukemia and other autoimmune diseases or (b) the inhibition of protein tyrosine kinases or Janus Kinase 3 (JAK3) in a mammal, including a human, comprising an amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof, effective in such disorders or conditions and a pharmaceutically acceptable carrier 8 A pharmaceutical composition for (a) treating or preventing a disorder or condition selected from organ transplant rejection, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, leukemia and other autoimmune diseases or (b) the inhibition of protein tyrosine kinases or Janus Kinase 3 (JAK3) in a mammal, including a human, comprising an amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof, alone or in combination with one or more additional agents which modulate a mammalian immune system or with antimflammatory agents, effective in such disorders or conditions and a pharmaceutically acceptable carrier 9 A method for the inhibition of protein tyrosine kinases or Janus Kinase 3 (JAK3) in a mammal, including a human, comprising administering to said mammal an effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof 10 A method for treating or preventing a disorder or condition selected from organ transplant rejection, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, leukemia and other autoimmune diseases in a mammal, including a human, comprising administering to said mammal an amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof, effective in treating such a condition 11 A method for the inhibition of protein tyrosine kinases or Janus Kinase 3 (JAK3) in a mammal, including a human, comprising administering to said mammal an effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof alone or in combination with one or more additional agents which modulate a mammalian immune system or with antimflammatory agents 12 A method for treating or preventing a disorder or condition selected from organ transplant rejection, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, leukemia and other autoimmune diseases in a mammal, including a human, comprising administering to said mammal an amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof, alone or in combination with one or more additional agents which modulate a mammalian immune system or with antimflammatory agents, effective in treating such a condition

Inventors: BLUMENKOPF TODD ANDREW, BROWN MATTHEW FRANK, CHANGELIAN PAUL STEVEN, FLANAGAN MARK EDWARD, BLUMENKOPF, TODD, ANDREW, BROWN, MATTHEW, FRANK, CHANGELIAN, PAUL, STEVEN, FLANAGAN, MARK, EDWARD
Applicants: BLUMENKOPF TODD ANDREW, BROWN MATTHEW FRANK, CHANGELIAN PAUL STEVEN, FLANAGAN MARK EDWARD, PFIZER PROD INC, BLUMENKOPF, TODD, ANDREW, BROWN, MATTHEW, FRANK, CHANGELIAN, PAUL, STEVEN, FLANAGAN, MARK, EDWARD, PFIZER PRODUCTS INC.
Application year: 1999
Main classification: C07D487
IPC codes: A61K31, A61P1, A61P3, A61P5, A61P11, A61P17, A61P19, A61P25, A61P29, A61P35, A61P37, C07D487, C07D519