Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3]([C:5]1[N:9]=[CH:8][N:7]([CH:10]2[CH:14]([O:15]C(=O)C3C=CC=CC=3)[CH2:13][CH:12]([O:24][CH2:25][P:26]([O:31]CC)([O:28]CC)=[O:27])[O:11]2)[N:6]=1)=O.Br[Si](C)(C)C.[N:39]1C(C)=CC=CC=1C.N>CC#N>[C:3]([C:5]1[N:9]=[CH:8][N:7]([CH:10]2[O:11][CH:12]([O:24][CH2:25][P:26](=[O:27])([OH:28])[OH:31])[CH2:13][CH:14]2[OH:15])[N:6]=1)(=[O:2])[NH2:39]
Reactant: Cc1cccc(C)n1
Reactant: CCOP(=O)(COC1CC(OC(=O)c2ccccc2)C(n2cnc(C(=O)OC)n2)O1)OCC
Agent: C[Si](C)(C)Br
Agent: N
Solvent: CC#N
Product: NC(=O)c1ncn(C2OC(OCP(=O)(O)O)CC2O)n1
Temperature: 25 °C
Reaction time: 10 h

Procedure:
The 1-[3-benzoyloxy-5-(diethoxy-phosphorylmethoxy)-tetrahydrofuran-2-yl]-1H-[1,2,4]triazole-3-carboxylic acid methyl ester (60 mg. 0.124 mmol) was dissolved in MeCN (1.5 mL). Bromotrimethylsilane (0.164 mL, 1.24 mmol) and 2,6-lutidine (0.043 mL, 0.372 mmol) were added and the mixture stirred at ambient temperature for 10 h. The solvents were removed in vacuo and the product isolated by C-18 HPLC. To this was then added ammonia (7 N in MeOH, 4 mL) and the mixture stirred overnight. The title compound was isolated by C-18 HPLC. 1H NMR (300 MHz, D2O) ppm 8.65 (s, 1H), 5.95 (d, 1H, J=2.4 Hz), 5.49-5.52 (m, 1H), 4.81-4.89 (m, 1H), 3.47-3.70 (m, 2H), 2.27-2.32 (m, 2H). 31P NMR (121.4 MHz, D2O) ppm 15.0. LRMS (ESI) M-H C8H12N4O7P requires 307.0 Found 307.0.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([NH:10][CH2:11][CH2:12][C:13]([O:15]CC)=[O:14])=[O:9])=[CH:4][CH:3]=1.[CH2:18]([C:20]1[C:24]([CH:25](O)[CH2:26][CH:27]([CH3:29])[CH3:28])=[CH:23][N:22]([C:31]2[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=2)[N:21]=1)[CH3:19]>>[CH2:18]([C:20]1[C:24]([CH:25]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]([NH:10][CH2:11][CH2:12][C:13]([OH:15])=[O:14])=[O:9])=[CH:6][CH:7]=2)[CH2:26][CH:27]([CH3:29])[CH3:28])=[CH:23][N:22]([C:31]2[CH:32]=[CH:33][C:34]([O:37][CH3:38])=[CH:35][CH:36]=2)[N:21]=1)[CH3:19]
Reactant: CCc1nn(-c2ccc(OC)cc2)cc1C(O)CC(C)C
Reactant: CCOC(=O)CCNC(=O)c1ccc(N)cc1
Product: CCc1nn(-c2ccc(OC)cc2)cc1C(CC(C)C)Nc1ccc(C(=O)NCCC(=O)O)cc1
Yield: 24.1 %

Procedure:
Using in 1-[3-ethyl-1-(4-methoxyphenyl)-1H-pyrazol-4-yl]-3-methylbutan-1-ol (0.5 g) synthesized above and ethyl 3-{[(4-aminophenyl)carbonyl]amino}propanoate (0.41 g) synthesized in Example 1(2) and in the same manner as in Example 1(7), the title object compound (0.2 g, 25%) was obtained as a white solid.
Reaction SMILES: [C:1]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1Cl)=[CH:13][CH:12]=[CH:11][C:10]=2[CH3:17])(=[O:5])[CH2:2][CH2:3][CH3:4].[CH3:18][O:19][C:20]1[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][C:21]=1[NH2:22]>O1CCOCC1>[C:1]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[NH:22][C:21]1[CH:23]=[C:24]([CH3:27])[CH:25]=[CH:26][C:20]=1[O:19][CH3:18])=[CH:13][CH:12]=[CH:11][C:10]=2[CH3:17])(=[O:5])[CH2:2][CH2:3][CH3:4]
Reactant: COc1ccc(C)cc1N
Reactant: CCCC(=O)c1cnc2c(C)cccc2c1Cl
Solvent: C1COCCO1
Product: CCCC(=O)c1cnc2c(C)cccc2c1Nc1cc(C)ccc1OC
Yield: 53.1 %

Procedure:
3-Butyryl-4-chloro-8-methylquinoline (1.77 g, 7.14 mmol) and 2-methoxy-5-methylaniline (1.47 g, 10.7 mmol) in dioxan (10 ml) were heated at reflux for 30 minutes, then evaporated and converted to free base. Recrystallisation from methanol and then from ethyl acetate/petroleum ether gave 3-butyryl-4-(2-methoxy-5-methylphenylamino)-8-methylquinoline (1.32 g), m.p. 136°-138°.
Reaction SMILES: [CH3:1][O:2][P:3]([C:7]1[CH:21]=[C:20]([F:22])[CH:19]=[CH:18][C:8]=1[CH2:9][NH:10]C(=O)OC(C)(C)C)([O:5][CH3:6])=[O:4].[F:23][C:24]([F:29])([F:28])[C:25]([OH:27])=[O:26]>ClCCl>[F:23][C:24]([F:29])([F:28])[C:25]([OH:27])=[O:26].[NH2:10][CH2:9][C:8]1[CH:18]=[CH:19][C:20]([F:22])=[CH:21][C:7]=1[P:3](=[O:4])([O:5][CH3:6])[O:2][CH3:1]
Reactant: COP(=O)(OC)c1cc(F)ccc1CNC(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COP(=O)(OC)c1cc(F)ccc1CN
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of tert-butyl 2-(dimethoxyphosphoryl)-4-fluorobenzylcarbamate (0.140 g, 0.42 mmol) in dichloromethane (5 ml) was treated with trifluoroacetic acid (5 ml) and the resulting mixture was stirred at 25° C. for 1 h. The solvent was then evaporated in vacuo to give the title amine salt as an amorphous white solid. MS (ESI+) m/z 234 [M+H+].
Reaction SMILES: [C:1]([Si:5]([CH3:24])([CH3:23])[O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13](=[N:21][OH:22])[CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2].C[O:26][C:27]([C:29]1([CH3:32])[CH2:31][CH2:30]1)=O>>[C:1]([Si:5]([CH3:24])([CH3:23])[O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:14]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:27]([C:29]3([CH3:32])[CH2:31][CH2:30]3)([OH:26])[O:22][N:21]=2)=[CH:9][CH:8]=1)([CH3:2])([CH3:4])[CH3:3]
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc(C(Cc2ccccc2)=NO)cc1
Reactant: COC(=O)C1(C)CC1
Product: CC1(C2(O)ON=C(c3ccc(O[Si](C)(C)C(C)(C)C)cc3)C2c2ccccc2)CC1

Procedure:
The synthetic intermediate 3-[4-(tert-butyl-dimethyl-silanyloxy)-phenyl]-5-(1-methyl-cyclopropyl)-4-phenyl -4,5-dihydro-isoxazol-5-ol (0.833 g) is prepared from Example 1, Compound B and 1-methyl-cyclopropanecarboxylic acid methyl ester by the general method described in Step A of Example 35.
Reaction SMILES: [C:1]1([CH:7]([O:14][C:15]([C:17]23[C:28]4([CH:30]=[O:31])[CH2:29][CH:20]([C:21]2([CH2:33][O:34][C:35]25[CH:44]([O:45][Si:46]([C:49]([CH3:52])([CH3:51])[CH3:50])([CH3:48])[CH3:47])[CH:41]6[CH:42]([OH:43])[CH:37]([CH:38]([O:40]6)[O:39]2)[O:36]5)[CH2:22][CH:23]2[CH:27]4[CH2:26][CH2:25][CH:24]2[CH3:32])[CH:19]=[C:18]3[CH:53]([CH3:55])[CH3:54])=[O:16])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].Br[CH2:59][CH:60]=[C:61]([CH3:63])[CH3:62]>CN(C)C=O>[C:1]1([CH:7]([O:14][C:15]([C:17]23[C:28]4([CH:30]=[O:31])[CH2:29][CH:20]([C:21]2([CH2:33][O:34][C:35]25[CH:44]([O:45][Si:46]([C:49]([CH3:52])([CH3:51])[CH3:50])([CH3:48])[CH3:47])[CH:41]6[CH:42]([O:43][CH2:59][CH:60]=[C:61]([CH3:63])[CH3:62])[CH:37]([CH:38]([O:40]6)[O:39]2)[O:36]5)[CH2:22][CH:23]2[CH:27]4[CH2:26][CH2:25][CH:24]2[CH3:32])[CH:19]=[C:18]3[CH:53]([CH3:55])[CH3:54])=[O:16])[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(C)C1=CC2CC3(C=O)C4CCC(C)C4CC2(COC24OC5OC(C(O)C5O2)C4O[Si](C)(C)C(C)(C)C)C13C(=O)OC(c1ccccc1)c1ccccc1
Reactant: CC(C)=CCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)=CCOC1C2OC3(OCC45CC6C(C)CCC6C6(C=O)CC4C=C(C(C)C)C65C(=O)OC(c4ccccc4)c4ccccc4)OC2OC1C3O[Si](C)(C)C(C)(C)C
Reaction time: 0.25 h

Procedure:
50 mg of compound (6) was dissolved in 0.4 ml of dry dimethylformamide under a nitrogen atmosphere and mixed with about 5 mg of sodium hydride under cooling with ice. After 15 minutes, 37.4 ml of 4-bromo-2-methyl2-butene was added, and the reaction solution was stirred under cooling with ice for 50 minutes. The reaction solution was allowed to react at room temperature for another 20 minutes under stirring. Then, the reaction solution was charged onto a silica gel column (Kieselgel 60, Merck, 1.5φ×19 cm) and eluted with n-hexane-ethyl acetate (10:1) to give 34.4 mg of compound (42) as a colorless oily substance.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([F:18])=[C:6]([C@:8]2([CH3:17])[C:13]([F:15])([F:14])[CH2:12][O:11][C:10]([NH2:16])=[N:9]2)[CH:7]=1.[F:19][C:20]([F:36])([C:32]([F:35])([F:34])[F:33])[CH2:21][O:22][C:23]1[CH:24]=[CH:25][C:26]([C:29](O)=[O:30])=[N:27][CH:28]=1>>[NH2:16][C:10]1[O:11][CH2:12][C:13]([F:14])([F:15])[C@:8]([C:6]2[CH:7]=[C:2]([NH:1][C:29]([C:26]3[CH:25]=[CH:24][C:23]([O:22][CH2:21][C:20]([F:19])([F:36])[C:32]([F:33])([F:34])[F:35])=[CH:28][N:27]=3)=[O:30])[CH:3]=[CH:4][C:5]=2[F:18])([CH3:17])[N:9]=1
Reactant: O=C(O)c1ccc(OCC(F)(F)C(F)(F)F)cn1
Reactant: C[C@]1(c2cc(N)ccc2F)N=C(N)OCC1(F)F
Product: C[C@]1(c2cc(NC(=O)c3ccc(OCC(F)(F)C(F)(F)F)cn3)ccc2F)N=C(N)OCC1(F)F

Procedure:
The condensation of (R)-4-(5-amino-2-fluoro-phenyl)-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine (intermediate XI-1) and 5-(2,2,3,3,3-pentafluoro-propoxy)-pyridine-2-carboxylic acid following procedure I yielded the title compound as a white solid. MS (ISP): m/z=513.1 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[C:5]2[S:10][C:9]([CH:11]=[C:12]3[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)=[CH:8][C:6]=2[N:7]=1.[CH:24](O)=O.C=O>O.ClCCl>[Cl:1][C:2]1[N:3]=[C:4]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[C:5]2[S:10][C:9]([CH:11]=[C:12]3[CH2:13][CH2:14][N:15]([CH3:24])[CH2:16][CH2:17]3)=[CH:8][C:6]=2[N:7]=1
Reactant: O=CO
Reactant: Clc1nc(N2CCOCC2)c2sc(C=C3CCNCC3)cc2n1
Agent: C=O
Solvent: ClCCl
Solvent: O
Product: CN1CCC(=Cc2cc3nc(Cl)nc(N4CCOCC4)c3s2)CC1
Temperature: 60 °C
Reaction time: 16 h

Procedure:
To a mixture of 2-chloro-4-morpholin-4-yl-6-piperidin-4-ylidenemethyl-thieno[3,2-d]pyrimidine (500 mg) and formic acid (2.5 mL) at room temperature was added formaldehyde (0.5 mL of a 37 wt % solution in water). The reaction mixture was stirred at 60° C. for 16 h. The mixture was then diluted with dichloromethane (2 mL) and washed with 2 M aqueous sodium hydroxide solution (20 mL) and brine (20 mL), dried (MgSO4), reduced in vacuo and purified by column chromatography to give 2-chloro-6-(1-methyl-piperidin-4-ylidenemethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine as a yellow solid (0.15 g).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N:14]([CH3:31])[C:15](=[O:30])[C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([C:26]([F:29])([F:28])[F:27])[CH:17]=2)=[C:4]([OH:32])[CH:3]=1.Br[CH2:34][C:35]#[N:36]>>[C:35]([CH2:34][O:32][C:4]1[CH:3]=[C:2]([F:1])[CH:7]=[CH:6][C:5]=1[C:8]1[CH:13]=[CH:12][N:11]=[CH:10][C:9]=1[N:14]([CH3:31])[C:15](=[O:30])[C:16]1[CH:17]=[C:18]([C:26]([F:27])([F:28])[F:29])[CH:19]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:21]=1)#[N:36]
Reactant: CN(C(=O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1cnccc1-c1ccc(F)cc1O
Reactant: N#CCBr
Product: CN(C(=O)c1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1cnccc1-c1ccc(F)cc1OCC#N

Procedure:
The title compound was prepared in analogy to example 49, from N-[4-(4-fluoro-2-hydroxy-phenyl)-pyridin-3-yl]-N-methyl-3,5-bis-trifluoromethyl-benzamide (example 48) and bromoacetonitrile (CAS RN 590-17-0). Yellow solid (32%). MS (ESI): m/z=497.8 [M+H]+.
Reaction SMILES: C(N(CC)CC)C.[Cl:8][C:9]1[CH:10]=[C:11]([NH:16][C:17](=[O:23])[NH:18][CH2:19][C:20]([OH:22])=O)[CH:12]=[C:13]([Cl:15])[CH:14]=1.Cl.[CH:25]([N:28]=[C:29]=[O:30])([CH3:27])[CH3:26]>ClC1C=CC=CC=1>[CH:25]([NH:28][C:29]([N:18]1[CH2:19][C:20](=[O:22])[N:16]([C:11]2[CH:12]=[C:13]([Cl:15])[CH:14]=[C:9]([Cl:8])[CH:10]=2)[C:17]1=[O:23])=[O:30])([CH3:27])[CH3:26]
Reactant: O=C(O)CNC(=O)Nc1cc(Cl)cc(Cl)c1
Reactant: CC(C)N=C=O
Agent: Cl
Solvent: CCN(CC)CC
Solvent: Clc1ccccc1
Product: CC(C)NC(=O)N1CC(=O)N(c2cc(Cl)cc(Cl)c2)C1=O
Temperature: 50 °C
Reaction time: 4 h
Yield: 100.6 %

Procedure:
101 g of triethylamine are added to a suspension of 263 g of 2-[3-(3,5-dichlorophenyl)-ureido]-acetic acid in 2,000 cm3 of chlorobenzene and 300 g of isopropyl isocyanate, which has been heated to 50° C, and the mixture is stirred for 4 hours at 80°-90°. After cooling, the reaction mixture is stirred for 30 minutes with 500 cm3 of a 7% strength (weight/volume) aqueous solution of hydrochloric acid. The organic solution is decanted, dried and concentrated under reduced pressure. 332 g of 1-isopropylcarbamoyl-3-(3,5-dichlorophenyl)-hydantoin melting at 130° C are thus obtained.
Reaction SMILES: Br[C:2]1[C:25]([F:26])=[CH:24][C:5]2[O:6][C:7]([C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=3[Cl:23])([C:9]3[CH:14]=[CH:13][C:12]([F:15])=[CH:11][CH:10]=3)[O:8][C:4]=2[CH:3]=1.C([Li])CCC.[C:32](=[O:34])=[O:33]>C(OCC)C>[Cl:23][C:17]1[CH:18]=[C:19]([Cl:22])[CH:20]=[CH:21][C:16]=1[C:7]1([C:9]2[CH:10]=[CH:11][C:12]([F:15])=[CH:13][CH:14]=2)[O:6][C:5]2[CH:24]=[C:25]([F:26])[C:2]([C:32]([OH:34])=[O:33])=[CH:3][C:4]=2[O:8]1
Reactant: O=C=O
Reactant: Fc1ccc(C2(c3ccc(Cl)cc3Cl)Oc3cc(F)c(Br)cc3O2)cc1
Agent: [Li]CCCC
Solvent: CCOCC
Product: O=C(O)c1cc2c(cc1F)OC(c1ccc(F)cc1)(c1ccc(Cl)cc1Cl)O2
Temperature: 20 °C
Reaction time: 1 h
Yield: 70.4 %

Procedure:
To a cooled (-78° C.) solution of 5-bromo-2-(2,4-dichloro-phenyl)-6-fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxole (16.5 g, 36.0 mmol) in diethyl ether (250 mL) was slowly added a solution of n-butyl lithium in hexanes (1.6M, 23 mL, 36.0 mmol, 1.0 eq.). After 1 h at −78° C., solid carbon dioxide (50 g approx.) was added to the solution and the reaction was allowed to warm up to 20° C. After 16 h at 20° C. the reaction mixture was partitioned between water (150 mL), ethyl acetate (1.5 L) and hydrochloric acid (1N, 150 mL). The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with water. The volatiles were removed in vacuo. Purification by flash chromatography afforded the title compound (10.73 g, 69%) as a light yellow solid.
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]3[C:11](=[O:21])[C:12]([CH3:20])([C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)[S:13][C:6]3=[CH:5][C:4]=2[CH:3]=1.[OH-:22].[Na+]>>[OH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([S:13][C:12]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([CH3:20])[C:11]([OH:21])=[O:22])=[CH:5]2
Reactant: [OH-]
Reactant: CC1(c2ccccc2)Sc2cc3cc(O)ccc3n2C1=O
Agent: [Na+]
Product: CC(Sc1cc2cc(O)ccc2[nH]1)(C(=O)O)c1ccccc1
Yield: 71 %

Procedure:
To the 7-hydroxy-2-methyl-2-phenylthiazolo[3,2-a]indol-3(2H)-one (3.65 g), a 2N sodium hydroxide solution (70 ml) was added, and the mixture was heated and refluxed for 30 minutes. The reaction mixture was allowed to cool, and was washed with ethyl acetate. The water layer was acidified with 6N hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with water, and a saturated aqueous sodium chloride solution, and was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (diluting solvent: chloroform/methanol=4:1), and recrystallized from acetonitrile to give 2.77 g (yield: 71%) of the desired product compound as a brown powder. The melting point was 179.5-181.5° C.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[CH:10][C:11]([NH2:14])=[N:12][CH:13]=2)[CH2:4][CH2:3]1.CS([C:18]1[N:23]=[CH:22][C:21]2=[CH:24][CH:25]=[C:26]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[O:33][CH3:34])[N:20]2[N:19]=1)=O.[F-].[Cs+].C(N(CC)C(C)C)(C)C.C(O)(C)(C)C>>[CH3:34][O:33][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=1[C:26]1[N:20]2[C:21]([CH:22]=[N:23][C:18]([NH:14][C:11]3[CH:10]=[CH:9][C:8]([N:5]4[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]4)=[CH:13][N:12]=3)=[N:19]2)=[CH:24][CH:25]=1
Reactant: CN1CCN(c2ccc(N)nc2)CC1
Reactant: COc1ccccc1-c1ccc2cnc(S(C)=O)nn12
Agent: [Cs+]
Agent: [F-]
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(C)(C)O
Product: COc1ccccc1-c1ccc2cnc(Nc3ccc(N4CCN(C)CC4)cn3)nn12
Temperature: 120 °C

Procedure:
Into a 8-dram vial, 5-(4-Methyl-piperazin-1-yl)-pyridin-2-ylamine (0.154 g, 0.804 mmol), 2-Methanesulfinyl-7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazine (0.105 g, 0.365 mmol), Cesium fluoride (0.139 g, 0.914 mmol), N,N-Diisopropylethylamine (0.1400 mL, 0.8039 mmol) and tert-Butyl alcohol (2.00 mL, 20.9 mmol) were added. The reaction was heated at 120° C. overnight. LCMS suggested presence of desired product. The reaction mixture was purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN. The collected fractions were lyophilized to give [7-(2-Methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-yl]-[5-(4-methyl-piperazin-1-yl)-pyridin-2-yl]-amine as a yellow solid (30 mg, 22%). LCMS (E/I+) 416.18 (M+H). NMR 1H (DMSO-d6)-9.80 (s, 1H), 9.72 (bs, 1H), 9.01 (s, 1H), 7.99 (s, 1H), 7.90 (d, 1H, J=9.58 Hz), 7.80 (d, 1H, J=7.49), 7.53 (d, 1H, J=9.38 Hz), 7.47 (d, 1H, J=7.59 Hz), 7.24 (d, 1H, J=8.04 Hz), 7.14 (t, 1H, J=7.15 Hz), 7.01 (s, 2H), 3.80 (bs, 5H), 3.55 (d, 2H, J=11.72 Hz), 3.19 (q, 2H, J=10.34 Hz), 2.96 (t, 2H, J=11.72 Hz), 2.83 (s, 3H).
Reaction SMILES: C(N(CC)CC)C.[Br:8][C:9]1[C:18]([O:19][CH2:20][C:21]([O:23][CH3:24])=[O:22])=[CH:17][CH:16]=[C:15]2[C:10]=1[CH:11]=[CH:12][C:13]([CH2:25][NH3+:26])=[CH:14]2.[Cl-].[C:28]1([N:34]2[C:38]([CH2:39][CH2:40][CH3:41])=[C:37]([C:42](Cl)=[O:43])[CH:36]=[N:35]2)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>C(Cl)Cl>[CH3:24][O:23][C:21](=[O:22])[CH2:20][O:19][C:18]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH2:25][NH:26][C:42]([C:37]3[CH:36]=[N:35][N:34]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[C:38]=3[CH2:39][CH2:40][CH3:41])=[O:43])[CH:14]=2)[C:9]=1[Br:8]
Reactant: CCCc1c(C(=O)Cl)cnn1-c1ccccc1
Reactant: COC(=O)COc1ccc2cc(C[NH3+])ccc2c1Br
Agent: [Cl-]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCc1c(C(=O)NCc2ccc3c(Br)c(OCC(=O)OC)ccc3c2)cnn1-c1ccccc1
Reaction time: 17 h
Yield: 95 %

Procedure:
Triethylamine (0.192 mL, 1.38 mmol) was added under nitrogen to a mixture of 5-bromo-6-methoxycarbonylmethoxy-naphthalen-2-ylmethyl-ammonium; chloride (0.25 g, 0.69 mmol), prepared in the previous step, and 1-phenyl-5-propyl-1H-pyrazole-4-carbonyl chloride (0.17 g, 0.69 mmol) in 20 mL of methylene chloride at room temperature. The reaction stirred under nitrogen for 17 h. The reaction was diluted with methylene chloride, extracted two times with water, two times with 5% sodium bicarbonate, dried (MgSO4) and the solvent removed under reduced pressure to give (1-Bromo-6-{[(1-phenyl-5-propyl-1H-pyrazole-4-carbonyl)-amino]-methyl}-naphthalen-2-yloxy)-acetic acid methyl ester (0.347 g, 95%) as a white solid, mp 144-146° C.
Reaction SMILES: [Cl:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4](Cl)[N:3]=1.Cl.[I:13][C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=1)[CH2:17][NH2:18].C(N(CC)CC)C>C(O)C>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4]([NH:18][CH2:17][C:16]2[CH:19]=[CH:20][CH:21]=[C:14]([I:13])[CH:15]=2)[N:3]=1
Reactant: Clc1nc(Cl)c2[nH]cnc2n1
Reactant: NCc1cccc(I)c1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCO
Product: Clc1nc(NCc2cccc(I)c2)c2[nH]cnc2n1
Yield: 56.8 %

Procedure:
A solution of 2,6-dichloropurine (Aldrich Chemical Co., 1 g, 5.3 mmol), 3-iodobenzylamine hydrochloride (1.7 g, 5.8 mmol), and triethylamine (2.2 ml, 15.35 mmol) in ethanol (10 ml) was stirred for 5 days at room temperature. The colorless solid formed was collected by suction, washed with small amount of cold ethanol, and dried to yield 2-chloro-N6 -(3-iodobenzyl)adenine (1.16 g, 60%): m.p. 222°-224° C.; mass (EI) 385: 1H NMR (DMSO-d6 d 4.59 (br s, 2H, --CH2), 7.13 (pseudo t, J=8.2 and 7.5 Hz, 1H, Bn), 7.36 (d, J=7.5 Hz, 1H, Bn), 7.61 (d, J=7.5 Hz, 1H, Bn), 7.74 (s, 1H, Bn), 8.14 (s, 1H, H-8), 8.76 (br s, 1H, exchangeable with D2O, NH), 13.14 (br s, 1H, exchangeable with D2O, NH). UV (MeOH) 1max 281.7, 257.5, 232.5 nm.
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][CH2:12][C@@H:13]([OH:25])[CH2:14][P:15]([CH2:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1)(=[O:17])[OH:16])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:26]([O:28][C:29](=[O:33])[O:30][CH2:31]Cl)[CH3:27]>C1(C)C=CC=CC=1.C(=O)([O-])[O-].[Ag+2]>[CH2:26]([O:28][C:29]([O:30][CH2:31][O:17][P:15]([CH2:14][CH:13]([OH:25])[CH2:12][NH:11][C:9]([O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:10])([CH2:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1)=[O:16])=[O:33])[CH3:27]
Reactant: CCOC(=O)OCCl
Reactant: O=C(NC[C@@H](O)CP(=O)(O)CC1CCCCC1)OCc1ccccc1
Agent: [Ag+2]
Agent: O=C([O-])[O-]
Solvent: Cc1ccccc1
Product: CCOC(=O)OCOP(=O)(CC(O)CNC(=O)OCc1ccccc1)CC1CCCCC1
Yield: 23.2 %

Procedure:
To a solution of ((R)-3-benzyloxycarbonylamino-2-hydroxy-propyl)-cyclohexylmethyl-phosphinic acid (1.0 g, 2.71 mmol) and carbonic acid chloromethyl ester ethyl ester (1.13 g, 8.16 mmol) in toluene (60 mL) was added silver carbonate (2.26 g, 8.16 mmol). The reaction mixture was heated at reflux for 3 h. The reaction mixture was then filtered and was concentrated in vacuo. Purification by gradient flash chromatography (methanol/methylene chloride) on a 35 g RediSep disposable column gave (3-benzyloxycarbonylamino-2-hydroxy-propyl)-cyclohexylmethyl-phosphinic acid ethoxycarbonyloxymethyl ester (300 mg, 0.63 mmol). 1H-NMR (CDCl3, 300 MHz): δ 7.35 (m, 5H), 5.65 (m, 2H), 5.45 (br s, 1H), 5.10 (s, 2H), 4.2 (m, 2H), 3.45 (dd, 1H), 3.20 (dd, 1H), 2.01-1.55 (m, 11H), 1.40-0.95 (m, 8H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([S:8]([C:11]2[CH:16]=[CH:15][C:14]3[C:17]4[CH2:22][CH2:21][NH:20][C:19]([CH2:24][N:25]5C(=O)C6C(=CC=CC=6)C5=O)([CH3:23])[C:18]=4[O:36][C:13]=3[CH:12]=2)(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.C(O)C.O.NN>>[F:1][C:2]1[CH:3]=[C:4]([S:8]([C:11]2[CH:16]=[CH:15][C:14]3[C:17]4[CH2:22][CH2:21][NH:20][C:19]([CH2:24][NH2:25])([CH3:23])[C:18]=4[O:36][C:13]=3[CH:12]=2)(=[O:9])=[O:10])[CH:5]=[CH:6][CH:7]=1
Reactant: CC1(CN2C(=O)c3ccccc3C2=O)NCCc2c1oc1cc(S(=O)(=O)c3cccc(F)c3)ccc21
Agent: NN
Solvent: O
Solvent: CCO
Product: CC1(CN)NCCc2c1oc1cc(S(=O)(=O)c3cccc(F)c3)ccc21
Reaction time: 4 h

Procedure:
To a solution of 2-[7-(3-fluoro-phenylsulfanyl)-1-methyl-1,2,3,4-tetrahydro-benzofuro[2,3-c]pyridin-1-ylmethyl]isoindole-1,3-dione (0.150 g, 0.317 mmol) in methanol (10.0 mL, 247 mmol) was added a solution of Oxone® (0.488 g, 0.794 mmol) in water (5.0 mL, 280 mmol) and the reaction mixture was stirred at room temperature overnight. After 3 h, the reaction was filtered, concentrated, and extracted with DCM/sat. aq. NaHCO3. The organic layer was dried, concentrated and purified by chromatography to afford 2-[7-(3-fluoro-benzenesulfonyl)-1-methyl-1,2,3,4-tetrahydro-benzofuro[2,3-c]pyridin-1-ylmethyl]isoindole-1,3-dione as an off-white solid. A suspension of 2-[7-(3-fluoro-benzenesulfonyl)-1-methyl-1,2,3,4-tetrahydro-benzofuro[2,3-c]pyridin-1-ylmethyl]isoindole-1,3-dione (0.015 g, 0.030 mmol) in ethanol (5.00 mL, 85.6 mmol) was refluxed with hydrazine monohydrate (0.040 mL, 0.80 mmol). After 4 h, the reaction was cooled, filtered, rinsed with MeOH, and the filtrate concentrated and dried under vacuum to afford a yellowish white solid. mp>250° C. dec.; MS m/z 375 [M+H]+. 1H-NMR (400 MHz, CDCl3): δ 1.5 (s, 3H), 2.7 (m, 2H), 3.15 (m, 1H), 3.36 (m, 1H), 4.0 (d, J=14 Hz, 1H), 4.15 (d, J=14 Hz, 1H), 7.2-8.0 (m, 7H)
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:23]#[N:24])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([CH:16]([CH2:20][CH3:21])[C:17](O)=[O:18])[C:10](=[O:22])[CH:9]=2)[CH:7]=1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]2[O:36][C:35](=[O:37])[NH:34][CH:33]=2)=[CH:28][CH:27]=1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:23]#[N:24])=[C:6]([C:8]2[C:13]([O:14][CH3:15])=[CH:12][N:11]([CH:16]([CH2:20][CH3:21])[C:17]([NH:25][C:26]3[CH:27]=[CH:28][C:29]([C:32]4[O:36][C:35](=[O:37])[NH:34][CH:33]=4)=[CH:30][CH:31]=3)=[O:18])[C:10](=[O:22])[CH:9]=2)[CH:7]=1
Reactant: Nc1ccc(-c2c[nH]c(=O)o2)cc1
Reactant: CCC(C(=O)O)n1cc(OC)c(-c2cc(Cl)ccc2C#N)cc1=O
Product: CCC(C(=O)Nc1ccc(-c2c[nH]c(=O)o2)cc1)n1cc(OC)c(-c2cc(Cl)ccc2C#N)cc1=O

Procedure:
87 mg (0.25 mmol) of 2-[4-(5-chloro-2-cyanophenyl)-5-methoxy-2-oxopyridin-1(2H)-yl]butanoic acid (racemate) and 60 mg (0.30 mmol, 1.2 eq.) of 5-(4-aminophenyl)-1,3-oxazol-2(3H)-one were reacted according to General Method 1. Yield: 23 mg (purity 93%, 17% of theory)
Reaction SMILES: Cl[P:2]1[S:6][CH2:5][CH2:4][O:3]1.[CH:7]([NH:10][CH:11]([CH3:13])[CH3:12])([CH3:9])[CH3:8]>CCCCC>[CH:7]([N:10]([P:2]1[S:6][CH2:5][CH2:4][O:3]1)[CH:11]([CH3:13])[CH3:12])([CH3:9])[CH3:8]
Reactant: CC(C)NC(C)C
Reactant: ClP1OCCS1
Solvent: CCCCC
Product: CC(C)N(C(C)C)P1OCCS1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Compound 1 (0.2 mol) is dissolved in n-pentane (300 mL) and diisopropylamine (0.4 mol) is added dropwise. The reaction mixture is stirred at room temperature for 30 minutes, after which dhisopropylamine hydrochloride is filtered off, solvent is evaporated under reduced pressure and crude product is purified by vacuum distillation. Product 2 is obtained as the fraction boiling at 70° C./0.1 mm Hg and is characterized by 31P NMR arid mass spectroscopy.