Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:16][C:17]2[CH:26]=[CH:25][CH:24]=[C:23]3[C:18]=2[CH:19]=[CH:20][C:21]([CH3:27])=[N:22]3)[C:9]2([C:12]([F:15])([F:14])[F:13])[CH2:11][O:10]2)=[C:4]([F:28])[C:3]=1[O:29][CH3:30].[CH2:31]([SH:33])[CH3:32].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([NH:16][C:17]2[CH:26]=[CH:25][CH:24]=[C:23]3[C:18]=2[CH:19]=[CH:20][C:21]([CH3:27])=[N:22]3)[C:9]([CH2:11][S:33][CH2:31][CH3:32])([C:12]([F:13])([F:15])[F:14])[OH:10])=[C:4]([F:28])[C:3]=1[O:29][CH3:30]
Reactant: CCS
Reactant: COc1c(Cl)ccc(C(Nc2cccc3nc(C)ccc23)C2(C(F)(F)F)CO2)c1F
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CCSCC(O)(C(Nc1cccc2nc(C)ccc12)c1ccc(Cl)c(OC)c1F)C(F)(F)F

Procedure:
Analogously to example 45 100 mg (0.25 mmol) {[4-chloro-2-fluoro-3-methoxyphenyl][2-(trifluoromethyl)oxiranyl]methyl}-(2-methylquinolin-5-yl)amine (example 13) are reacted with 0.24 ml of the 1 M ethanthiol solution under the presence of 148 mg Caesium carbonate in DMF. The typical work up after 2 hours yields 54 mg of the title compound after preparative thin layer chromatography on silica gel (acetone in hexane 50%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[N:12]=[C:13]=[O:14].C(N(CC)CC)C.[NH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[C:30]([C:34]([NH2:36])=[O:35])=[CH:31][NH:32][CH:33]=2)=[CH:25][CH:24]=1>O1CCCC1.ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[NH:12][C:13](=[O:14])[NH:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[C:30]([C:34]([NH2:36])=[O:35])=[CH:31][NH:32][CH:33]=2)=[CH:25][CH:24]=1
Reactant: O=C=Nc1cc(C(F)(F)F)ccc1F
Reactant: NC(=O)c1c[nH]cc1-c1ccc(N)cc1
Solvent: C1CCOC1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: NC(=O)c1c[nH]cc1-c1ccc(NC(=O)Nc2cc(C(F)(F)F)ccc2F)cc1
Temperature: 20 °C
Reaction time: 20 h

Procedure:
0.012 cm3 of 2-fluoro-5-trifluoromethylphenyl isocyanate and 0.012 cm3 of triethylamine are added at a temperature in the region of 20° C., under an argon atmosphere, to 0.017 g (84.48 mmol) of 4-(4-aminophenyl)-1H-pyrrole-3-carboxamide in suspension in 27 cm3 of tetrahydrofuran. After stirring for 20 hours at a temperature in the region of 20° C., the reaction mixture is concentrated to dryness under reduced pressure (2.7 kPa) to give a residue which is purified by flash chromatography [eluent: ethyl acetate/dichloromethane (95/5 by volume)]. After concentrating the fractions under reduced pressure, a yellow residue is obtained which is stirred in 5 cm3 of dichloromethane and then filtered and dried under reduced pressure (2.7 kPa) to give 22 mg of 4-{4-[3-(2-fluoro-5-trifluoromethylphenyl)-ureido]phenyl}-1H-pyrrole-3-carboxamide, in the form of a beige solid; 1H NMR (300 MHz, (CD3)2SO, —δ in ppm): from 6.57 to 7.02 (very broad m: 2H); 6.85 (broad t, J=2.5 Hz: 1H); 7.29 (broad t, J=2.5 Hz: 1H); from 7.33 to 7.43 (m; 5H); 7.49 (dd, J=10.5 and 8.5 Hz: 1H); 8.60 (dd, J=7.5 and 2.5 Hz: 1H); 9.31 (broad s: 1H); 9.58 (broad s: 1H); 11.2 (broad s: 1H); EI: m/z=406 (M+), m/z=205 (C8H3NOF4+), m/z=179 (C7H4NF4+) base peak, ES+: m/z=407 (MH+).
Reaction SMILES: [C:1]([CH2:4][O:5][C:6]1[CH:19]=[CH:18][C:9]([CH2:10][CH:11]2[S:15][C:14](=[O:16])[NH:13][C:12]2=[O:17])=[CH:8][CH:7]=1)(O)=O.[CH3:20][NH:21][C:22](=[O:30])[C:23]1[C:24](=[CH:26][CH:27]=[CH:28][CH:29]=1)[NH2:25].C1(C)C(C)=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[CH3:20][N:21]1[C:22](=[O:30])[C:23]2[C:24](=[CH:26][CH:27]=[CH:28][CH:29]=2)[N:25]=[C:1]1[CH2:4][O:5][C:6]1[CH:7]=[CH:8][C:9]([CH2:10][CH:11]2[S:15][C:14](=[O:16])[NH:13][C:12]2=[O:17])=[CH:18][CH:19]=1
Reactant: O=C(O)COc1ccc(CC2SC(=O)NC2=O)cc1
Reactant: CNC(=O)c1ccccc1N
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CO
Solvent: Cc1ccccc1C
Product: Cn1c(COc2ccc(CC3SC(=O)NC3=O)cc2)nc2ccccc2c1=O
Temperature: 175 °C

Procedure:
A suspension of 5-[4-[(carboxy)methoxy]benzyl]thiazolidine-2,4-dione obtained by following a procedure described in any of Examples 25-28 (100 g., 0.36 M), N-methyl anthranilamide (58.7 g, 0.39 M), xylene (100 ml) and p-toluenesulfonic acid (200 mg) was taken in a round bottom flask fitted with a mechanical stirrer, oil bath and Dean-Stark condenser. The reaction mixture was heated to reflux (Internal temperature 150-155° C., oil bath temperature 170-180° C.) for a period of 12-15 h while monitoring the reaction by TLC. After completion of the reaction, reaction mass was cooled to 80° C. and methanol (700 ml) was added slowly through a dropping funnel. The reaction mass was allowed to attain room temperature while stirring and the solid thus obtained was filtered and washed with methanol (150 ml) and dried at 100-120° C. for 1 h to afford 5-[4-[[3-methyl-4-oxo-3,4-dihydroquinazolin-2-yl]methoxy]benzyl]thiazolidine-2,4-dione as a white solid (95 g, Y=68%, P=98%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[O:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11][CH:10]2[CH2:23]OS(C)(=O)=O)[CH:5]=[CH:6][C:7]=1[Cl:8].[CH3:29][S-:30].[Na+]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[O:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:17])[CH2:11][CH:10]2[CH2:23][S:30][CH3:29])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: CC(C)(C)OC(=O)N1CCOC(c2ccc(Cl)c(Cl)c2)C(COS(C)(=O)=O)C1
Reactant: C[S-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CSCC1CN(C(=O)OC(C)(C)C)CCOC1c1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 61.5 %

Procedure:
To a solution of tert-butyl (6RS,7SR)-7-(3,4-dichlorophenyl)-6-{[(methylsulfonyl)oxy]methyl}-1,4-oxazepane-4-carboxylate (200 mg) in DMF (3 ml) was added sodium thiomethoxide (46.3 mg), and the mixture was stirred at room temperature for 16 hr. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with ethyl acetate. The diluted solution was washed with distilled water and brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography (hexane/ethyl acetate) to give the title compound (110 mg).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][C:3]=1/[CH:13]=[CH:14]/[C:15]([O:17]CC)=O>Cl.O1CCOCC1>[F:8][C:6]1[CH:7]=[C:2]2[C:3]([CH:13]=[CH:14][C:15](=[O:17])[NH:1]2)=[CH:4][C:5]=1[C:9]([F:12])([F:11])[F:10]
Reactant: CCOC(=O)/C=C/c1cc(C(F)(F)F)c(F)cc1N
Agent: Cl
Solvent: C1COCCO1
Product: O=c1ccc2cc(C(F)(F)F)c(F)cc2[nH]1
Temperature: 100 °C

Procedure:
To a stirring mixture of (E)-ethyl 3-(2-amino-4-fluoro-5-(trifluoromethyl)phenyl)acrylate in 4N HCl in dioxane (10 mL) was added concentrated HCl (2 mL). The resulting mixture was warmed to 100° C. overnight. The reaction mixture was cooled to rt and then slowly quenched with a cold saturated NaHCO3 solution until pH>7. A normal aqueous extraction with EtOAc was followed. The crude mixture was taken directly to the next reaction without further purification. Retention time (min)=1.887, method [1], MS(ESI) 232.0 (M+H).
Reaction SMILES: [Br:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([F:9])[C:7]=1[CH3:8].CN([CH:14]=[O:15])C.C[O-].[Na+]>O>[Br:1][C:2]1[C:3]([O:15][CH3:14])=[N:4][CH:5]=[C:6]([F:9])[C:7]=1[CH3:8]
Reactant: Cc1c(F)cnc(Cl)c1Br
Reactant: CN(C)C=O
Agent: C[O-]
Agent: [Na+]
Solvent: O
Product: COc1ncc(F)c(C)c1Br
Temperature: 80 °C
Reaction time: 2 h

Procedure:
3-bromo-2-chloro-5-fluoro-4-methylpyridine (340 mg) was added to DMF (1.8 mL). Sodium methoxide (28% solution in methanol, 5.4 mL) was added to the solution, and the mixture was stirred at 80° C. for two hours. Water was added to the reaction mixture. The precipitated solid was collected by filtration to give the title compound (240 mg).
Reaction SMILES: [Cl:1][CH:2]([Cl:17])[C:3]([F:16])([F:15])[O:4][C:5]1[CH:10]=[C:9]([CH3:11])[CH:8]=[CH:7][C:6]=1[N+:12]([O-:14])=[O:13].[Cl:18][S:19](O)(=[O:21])=[O:20]>>[Cl:17][CH:2]([Cl:1])[C:3]([F:15])([F:16])[O:4][C:5]1[C:6]([N+:12]([O-:14])=[O:13])=[CH:7][C:8]([S:19]([Cl:18])(=[O:21])=[O:20])=[C:9]([CH3:11])[CH:10]=1
Reactant: O=S(=O)(O)Cl
Reactant: Cc1ccc([N+](=O)[O-])c(OC(F)(F)C(Cl)Cl)c1
Product: Cc1cc(OC(F)(F)C(Cl)Cl)c([N+](=O)[O-])cc1S(=O)(=O)Cl

Procedure:
In a 500 ml stirred reaction flask equipped with thermometer, air condenser, dropping funnel and ice water bath was placed 50 ml of chlorosulfonic acid, and, while stirring at 0° to 10° C, there was added dropwise over a one-half hour period 17.2 g of 2-(2,2-dichloro-1,1-difluoroethoxy)-4-methyl-1-nitrobenzene. After stirring for 50 hours, the reaction mixture was poured over crushed ice. The organic phase was extracted with methylene chloride, and the extract was washed with dilute bicarbonate, decolorized with charcoal and dried. Evaporation of the solvent affored 10 g of 4-(2,2-dichloro-1,1-difluoroethoxy)-2-methyl-5-nitrobenzenesulfonyl chloride as a solid melting at 60°-61° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:14]=[CH:13][C:6]2[CH2:7][CH2:8][CH2:9][C@H:10](O)[CH2:11][C:5]=2[CH:4]=1.[C:15]1(=[O:25])[NH:19][C:18](=[O:20])[C:17]2=[CH:21][CH:22]=[CH:23][CH:24]=[C:16]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[CH3:1][O:2][C:3]1[CH:14]=[CH:13][C:6]2[CH2:7][CH2:8][CH2:9][C@@H:10]([N:19]3[C:18](=[O:20])[C:17]4=[CH:21][CH:22]=[CH:23][CH:24]=[C:16]4[C:15]3=[O:25])[CH2:11][C:5]=2[CH:4]=1
Reactant: O=C1NC(=O)c2ccccc21
Reactant: COc1ccc2c(c1)C[C@@H](O)CCC2
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COc1ccc2c(c1)C[C@H](N1C(=O)c3ccccc3C1=O)CCC2
Temperature: 25 °C
Reaction time: 48 h
Yield: 25.7 %

Procedure:
To a mixture of (S)-3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-6-ol (1.00 g), phthalimide (0.77 g), and triphenylphosphine (1.36 g) in dry tetrahydrofuran, was added dropwise a solution of diethyl azodicarboxylate (0.91 g) in dry tetrahydrofuran (3 ml) at 26° C.~33° C. The mixture was stirred at ambient temperature for 2 days. The solvent was evaporated in vacuo. Diethyl ether (30 ml) was added to the residue and the mixture was stirred and the resulting precipitates (triphenyl phosphinoxide) were removed by filtration. The filtrate was evaporated in vacuo. The residue was purified by column chromatography (silica gel, n-hexane:ethyl acetate=5:1) to give (R)-N-(3-methoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-6-yl)phthalimide as a white powder (0.43 g).
Reaction SMILES: [C:1]([NH:4][C:5]1[C:13]2[C:8](=[CH:9][C:10]([Cl:15])=[C:11]([Br:14])[CH:12]=2)[N:7](C(OCC)=O)[C:6]=1[C:21]([C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([CH3:29])[N:24]=1)=[O:22])(=[O:3])[CH3:2]>ClCCl.CO>[C:1]([NH:4][C:5]1[C:13]2[C:8](=[CH:9][C:10]([Cl:15])=[C:11]([Br:14])[CH:12]=2)[NH:7][C:6]=1[C:21]([C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([CH3:29])[N:24]=1)=[O:22])(=[O:3])[CH3:2]
Reactant: CCOC(=O)n1c(C(=O)c2cccc(C)n2)c(NC(C)=O)c2cc(Br)c(Cl)cc21
Solvent: CO
Solvent: ClCCl
Product: CC(=O)Nc1c(C(=O)c2cccc(C)n2)[nH]c2cc(Cl)c(Br)cc12

Procedure:
The title compound was prepared according to the procedure described in step 2 of Example 2 (Method A) from 3-acetylamino-5-bromo-6-chloro-1-(ethoxycarbonyl)-2-(6-methylpyridine-2-carbonyl)indole (step 2). m.p.: 234-236° C. (dichloromethane/methanol) 1H-NMR (DMSO-d6) δ: 12.01 (1H, br s), 10.26 (1H, br s), 8.21 (1H, s), 7.98 (1H, t, J=7.7 Hz), 7.86 (1H, d, J=7.7 Hz), 7.85 (1H, s), 7.57 (1H, d, J=7.7 Hz), 2.66 (3H, s), 1.99 (3H, s).
Reaction SMILES: O.C(O[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[C:13]([CH:15]=[O:16])=[O:14])CCC.[CH3:17][CH:18]([NH2:30])[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH3:29])[CH:21]=1>CS(C)=O>[CH3:17][CH:18]([N:30]=[C:15]([O:16][CH2:12][CH2:7][CH2:8][CH3:9])[C:13]([C:8]1[CH:7]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:14])[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[C:22]([O:28][CH3:29])[CH:21]=1
Reactant: CCCCOc1ccccc1C(=O)C=O
Reactant: COc1ccc(CC(C)N)cc1OC
Solvent: O
Solvent: CS(C)=O
Product: CCCCOC(=NC(C)Cc1ccc(OC)c(OC)c1)C(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
3.0 g of 2-n-butoxyphenylglyoxal hydrate (crude oil) are dissolved in 9 ml of dimethylsulfoxide, and 2.8 g of α-methyl-3,4-dimethoxyphenethylamine are added thereto. The mixture is stirred at room temperature for 30 minutes, whereby a solution of α-(α-methyl-3,4-dimethoxyphenylethylimino)-2-n-butoxyacetophenone in dimethylsulfoxide is obtained.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C@@H:15]([OH:34])[CH2:16][NH:17][C:18]([CH3:33])([CH3:32])[CH2:19][CH2:20][N:21]2[CH:25]=[C:24]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[N:23]=[CH:22]2)=[CH:11][C:10]=1[N+:35]([O-])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H][H]>O1CCCC1.C1(C)C=CC=CC=1.[Pt](=O)=O>[NH2:35][C:10]1[CH:11]=[C:12]([C@@H:15]([OH:34])[CH2:16][NH:17][C:18]([CH3:32])([CH3:33])[CH2:19][CH2:20][N:21]2[CH:25]=[C:24]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[N:23]=[CH:22]2)[CH:13]=[CH:14][C:9]=1[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(CCn1cnc(-c2ccccc2)c1)NC[C@H](O)c1ccc(OCc2ccccc2)c([N+](=O)[O-])c1
Reactant: [H][H]
Agent: O=[Pt]=O
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: CC(C)(CCn1cnc(-c2ccccc2)c1)NC[C@H](O)c1ccc(OCc2ccccc2)c(N)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 100 %

Procedure:
0.025 g (0.11 mmol) platinum(IV)oxide were added to a solution of 0.15 g (0.28 mmol) (R)-1-(4-benzyloxy-3-nitrophenyl)-2-[1,1-dimethyl-3-(4-phenylimidazol-1-yl)-propylamino]-ethanol in 10 mL tetrahydrofuran/toluene (1:1). The reaction mixture was shaken in an autoclave under a hydrogen pressure of 10 psi at ambient temperature for 16 h. The hydrogen pressure was released, the platinum(IV)oxide was filtered off and the filtrate was freed from solvent. 0.14 g (0.28 mmol, 99%) (R)-1-(3-amino-4-benzyloxyphenyl)-2-[1,1-dimethyl-3-(4-phenylimidazol-1-yl)-propylamino]-ethanol were obtained as a brown oil.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[N:3]=1.[CH:10]12[O:22][CH:13]([CH2:14][CH:15]1[S:16]([N:19]=[C:20]=[O:21])(=[O:18])=[O:17])[CH:12]=[CH:11]2.CCCCCC>ClCCl>[CH3:9][C:4]1[CH:5]=[C:6]([CH3:8])[N:7]=[C:2]([NH:1][C:20]([NH:19][S:16]([CH:15]2[CH:10]3[O:22][CH:13]([CH:12]=[CH:11]3)[CH2:14]2)(=[O:17])=[O:18])=[O:21])[N:3]=1
Reactant: Cc1cc(C)nc(N)n1
Reactant: O=C=NS(=O)(=O)C1CC2C=CC1O2
Solvent: CCCCCC
Solvent: ClCCl
Product: Cc1cc(C)nc(NC(=O)NS(=O)(=O)C2CC3C=CC2O3)n1
Temperature: 0 °C
Yield: 90.8 %

Procedure:
30.7 g (0.25 mole) of 2-amino-4,6-dimethylpyrimidine were dissolved in 350 ml of dichloromethane and a solution of 52 g (0.26 mole) of 7-oxabicyclo[2.2.1]hept-2-en-6-ylsulfonyl isocyanate (Diels-Alder adduct of vinylsulfonyl isocyanate and furan) in 100 ml of dichloromethane was added at 0° C. with stirring. The mixture was stirred a further 12 hours at room temperature, cooled to 0° C. and n-hexane was added. The precipitated reaction product was filtered off with suction, washed with n-hexane and dried. 73.6 g (90.8% of theory) of N-[(4,6-dimethylpyrimidin-2-yl)aminocarbonyl]-7-oxabicyclo[2.2.1]hept-2-en-6-ylsulfonamide having a melting point of 125°-145° C. were obtained.
Reaction SMILES: [C:1]([O:5][CH2:6][C@H:7]([CH3:10])[CH2:8]Br)([CH3:4])([CH3:3])[CH3:2].BrOBr.[C-:14]#[N:15].[Na+].CO>O>[C:1]([O:5][CH2:6][C@H:7]([CH3:10])[CH2:8][C:14]#[N:15])([CH3:4])([CH3:3])[CH3:2]
Reactant: C[C@H](CBr)COC(C)(C)C
Reactant: [C-]#N
Agent: BrOBr
Agent: [Na+]
Solvent: O
Solvent: CO
Product: C[C@H](CC#N)COC(C)(C)C
Yield: 64.6 %

Procedure:
A mixture of 23.1 g. (0.11 mole) of bromo ether (S)-(+)-3-tert. butoxy-2-methyl-1-bromopropane and 11.07 g. (0.225 mole) of sodium cyanide in 144 ml. of methanol and 36 ml. of water was stirred and refluxed for 17 hours. After cooling, the reaction mixture was diluted with water and worked up by extraction with CH2Cl2 in the manner of Example 1. The crude product was chromatographed on 500 g. of silica gel. Elution with 9:1 parts by volume and 4:1 parts by volume hexane-ether followed by evaporative distillation gave (R)-(+)-4-tert. butoxy-3-methylbutyronitrile (11.03 g.; 64.5%) as a colorless liquid, b.p. 88°-90° C. (bath temperature) (11 mm Hg.); [α]25D+7.41° (c 1.8, C6H6).
Reaction SMILES: [CH3:1][N:2]([CH3:32])[C:3]([C:5]1[N:26]([CH:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)[C:8]2[N:9]=[C:10]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([N:20]4[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]4)=[CH:16][N:15]=3)[N:11]=[CH:12][C:7]=2[CH:6]=1)=[O:4].Br[CH:34]1[CH2:38][CH2:37][CH2:36][CH2:35]1>>[CH3:1][N:2]([CH3:32])[C:3]([C:5]1[N:26]([CH:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)[C:8]2[N:9]=[C:10]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([N:20]4[CH2:21][CH2:22][N:23]([CH:34]5[CH2:38][CH2:37][CH2:36][CH2:35]5)[CH2:24][CH2:25]4)=[CH:16][N:15]=3)[N:11]=[CH:12][C:7]=2[CH:6]=1)=[O:4]
Reactant: CN(C)C(=O)c1cc2cnc(Nc3ccc(N4CCNCC4)cn3)nc2n1C1CCCC1
Reactant: BrC1CCCC1
Product: CN(C)C(=O)c1cc2cnc(Nc3ccc(N4CCN(C5CCCC5)CC4)cn3)nc2n1C1CCCC1
Yield: 73.5 %

Procedure:
Following General Procedure D, 7-cyclopentyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (100 mg, 0.230 mmol) and bromo cyclopentane (103 mg, 0.691 mmol) gave 7-cyclopentyl-2-[5-(4-cyclopentyl-piperazin-1-yl)-pyridin-2-ylamino]-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid dimethylamide (85 mg, 71%). MS (ESI) m/z 503.3 (M+H)+
Reaction SMILES: I.[NH:2]=[C:3]1[NH:7][CH2:6][CH2:5][NH:4]1.[H-].[Li+].[Br:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([Br:17])[C:12]=1[N:18]=[C:19]=[O:20]>CN(C)C=O>[Br:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([Br:17])[C:12]=1[NH:18][C:19]([N:2]=[C:3]1[NH:7][CH2:6][CH2:5][NH:4]1)=[O:20]
Reactant: N=C1NCCN1
Reactant: O=C=Nc1c(Br)cccc1Br
Agent: I
Agent: [H-]
Agent: [Li+]
Solvent: CN(C)C=O
Product: O=C(N=C1NCCN1)Nc1c(Br)cccc1Br
Temperature: 25 °C
Reaction time: 8 h

Procedure:
In a manner similar to that described in Examples II and III, a solution of 12.0 grams (0.0563 mole) of 2-iminoimidazolidine hydroiodide in 50 milliliters of dry dimethylformamide is added dropwise with cooling and under an atmosphere of nitrogen to a suspension of 447 milligrams (0.0563 mole) of lithium hydride in 50 milliliters of dry dimethylformamide. After completion of the addition the mixture is allowed to warm to room temperature over a period of about half an hour, then cooled to 0°-5° C., and a solution of 7.8 grams (0.0282 mole) of 2,6-dibromophenyl isocyanate in 25 milliliters of dry dimethylformamide is added dropwise over a two hour period while maintaining the cooled temperature range. The mixture is then allowed to warm to room temperature and stirred overnight under nitrogen to obtain the desired N-(2,6-dibromophenyl)-N'-(2-imidazolidinylidene)urea product in the reaction mixture. The product is recovered from the reaction mixture by pouring the mixture into 400 milliliters of ice water, acidifying with 10 percent hydrochloric acid to pH below 3, filtering to remove impurities, saturating the filtrate with solid sodium chloride and basifying with potassium carbonate to a pH of 8-9 to precipate the N-(2,6-dibromophenyl)-N'-(2-imidazolidinylidene)urea product as a white solid, m.p. 185°-190° C. (dec.)
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:21]=[CH:20][CH:19]=[CH:18][C:4]=1[CH2:5][NH:6][C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([NH2:17])[CH:13]=2)[N:8]=1.C(N(CC)CC)C.ClC(O[C:34](=[O:40])OC(Cl)(Cl)Cl)(Cl)Cl.[CH3:41][N:42]1[CH2:47][CH2:46][CH:45]([NH2:48])[CH2:44][CH2:43]1>O1CCCC1>[CH3:1][O:2][C:3]1[CH:21]=[CH:20][CH:19]=[CH:18][C:4]=1[CH2:5][NH:6][C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][CH:11]=[C:12]([NH:17][C:34]([NH:48][CH:45]3[CH2:46][CH2:47][N:42]([CH3:41])[CH2:43][CH2:44]3)=[O:40])[CH:13]=2)[N:8]=1
Reactant: CN1CCC(N)CC1
Reactant: COc1ccccc1CNc1ccc2cc(N)ccc2n1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: COc1ccccc1CNc1ccc2cc(NC(=O)NC3CCN(C)CC3)ccc2n1
Temperature: 80 °C
Yield: 34.1 %

Procedure:
N2-(2-Methoxy-benzyl)-quinoline-2,6-diamine (example 10, step B, 65 mg, 0.233 mmol) was dissolved in tetrahydrofuran (3 ml) and triethylamine (0.052 mL, 0.512 mmol) was added. At 0° C. bis(trichloromethyl)carbonate (31 mg, 0.105 mmol) was added and the reaction mixture subsequently heated to 80° C. for 3 h. Upon cooling to ambient temperature triethylamine (0.052 mL, 0.512 mmol) and 1-methyl-piperidin-4-ylamine (27 mg, 0.233 mmol) were added and the whole reaction mixture was stirred over night at 50° C. After evaporation of the solvent, the residue was taken up in water and extracted with ethyl acetate. The combined organic phases were dried on sodium sulfate, filtered and the filtrate was evaporated. The crude product was purified by flash chromatography on silica gel (dichloromethane/methanol) and to yield the title compound as white solid (15 mg, 15%). MS: m/e=420.4 (M+H+).
Reaction SMILES: [Br:1][CH:2]([CH3:12])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8](I)=[CH:7][CH:6]=1.[CH2:13]([OH:17])[CH2:14][C:15]#[CH:16].CCN(CC)CC>ClCCl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Br:1][CH:2]([CH3:12])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:16]#[C:15][CH2:14][CH2:13][OH:17])=[CH:7][CH:6]=1
Reactant: CC(Br)COc1ccc(I)cc1
Reactant: C#CCCO
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(Br)COc1ccc(C#CCCO)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 31.7 %

Procedure:
To a solution of 4-(2-Bromopropoxy)-1-iodobenzene (10 g, 29 mmol), 3-butyn-1-ol (26 mL, 37 mmol), Cul (980 mg, 5.2 mmol) and dichlorobis(triphenylphosphine)palladium(II) (3.6 g, 5.2 mmol) in dichloromethane (40 mL) was added Et3N (6.0 mL, 44 mmol) dropwise. The reaction was stirred overnight at room temperature under Ar. The solvent was evaporated under reduced pressure and ethyl acetate was added to dissolve the compound, the solution was filtered over celite to remove most of the Pd. The crude product was purified by silica gel chromatography, eluted with hexane/ethyl acetate (2:1). 2.6 g of the title compound were obtained as a light brown solid.
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)[C:5]2[S:10][C:9](I)=[CH:8][C:6]=2[N:7]=1.[CH3:18][S:19]([C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[CH:26][CH:27]=1)(=[O:21])=[O:20].CC1(C)C(C)(C)OB([C:39]2[CH:40]=[C:41]3[CH:47]=[CH:46][NH:45][C:42]3=[N:43][CH:44]=2)O1>C([O-])([O-])=O.[Na+].[Na+].C(#N)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:18][S:19]([C:22]1[CH:23]=[C:24]([C:9]2[S:10][C:5]3[C:4]([N:12]4[CH2:17][CH2:16][O:15][CH2:14][CH2:13]4)=[N:3][C:2]([C:39]4[CH:40]=[C:41]5[CH:47]=[CH:46][NH:45][C:42]5=[N:43][CH:44]=4)=[N:7][C:6]=3[CH:8]=2)[CH:25]=[CH:26][CH:27]=1)(=[O:21])=[O:20]
Reactant: CS(=O)(=O)c1cccc(B(O)O)c1
Reactant: Clc1nc(N2CCOCC2)c2sc(I)cc2n1
Reactant: CC1(C)OB(c2cnc3[nH]ccc3c2)OC1(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC#N
Product: CS(=O)(=O)c1cccc(-c2cc3nc(-c4cnc5[nH]ccc5c4)nc(N4CCOCC4)c3s2)c1
Temperature: 150 °C

Procedure:
2-Chloro-6-iodo-4-morpholinothieno[3,2-d]pyrimidine 19 from Example 12 (0.2 g, 0.6 mmol), 3-(methylsulfonyl)phenylboronic acid (120 mg, 0.6 mmol), and bis(triphenylphosphine)palladium(II) dichloride (20 mg, 30 μmol) in 1M aqueous Na2CO3 (1 mL) and acetonitrile (1 mL) were heated to 100° C. in a sealed microwave reactor for 10 min. Upon completion, 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (210 mg, 0.87 mmol) and bis(triphenylphosphine)palladium(II) dichloride (20 mg, 30 μmol) were added and the mixture was heated to 150° C. in a sealed microwave reactor for 20 min. The mixture was extracted with EtOAc and CH2Cl2. The combined organics were concentrated to yield 418 after reverse phase HPLC purification (40 mg). MS (Q1) 492 (M)+