Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:10]=[CH:9][N:8]2[C:11](I)=[CH:12][N:13]=[C:7]2[CH:6]=1)=[O:4].CC1(C)C(C)(C)OB([C:23]2[CH:24]=[C:25]([NH:29][C:30]([NH:32][CH2:33][C:34]([F:37])([F:36])[F:35])=[O:31])[CH:26]=[CH:27][CH:28]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:35][C:34]([F:36])([F:37])[CH2:33][NH:32][C:30](=[O:31])[NH:29][C:25]1[CH:24]=[C:23]([C:11]2[N:8]3[CH:9]=[CH:10][C:5]([C:3]([OH:2])=[O:4])=[CH:6][C:7]3=[N:13][CH:12]=2)[CH:28]=[CH:27][CH:26]=1
Reactant: COC(=O)c1ccn2c(I)cnc2c1
Reactant: CC1(C)OB(c2cccc(NC(=O)NCC(F)(F)F)c2)OC1(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Solvent: O
Product: O=C(NCC(F)(F)F)Nc1cccc(-c2cnc3cc(C(=O)O)ccn23)c1
Temperature: 80 °C

Procedure:
To a solution of 3-Iodo-imidazo[1,2-a]pyridine-7-carboxylic acid methyl ester (3.02 g, 10 mmol) in DME (200 ml) was added 1-[3-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-3-(2,2,2-trifluoro-ethyl)-urea (4.13 g, 12 mmol), 1M Na2CO3 (80 ml) [reaction degassed by bubbling N2 through] followed by tetrakis(triphenylphosphine)palladium(0) (0.58 g, 0.5 mmol). The mixture was heated at 80° C. overnight, then diluted with water and extracted with CH2Cl2. The aqueous layer was neutralised and loaded onto a reverse phase (C18) SPE (Solid Phase Extraction) cartridge. The cartridge was washed with H2O (2 column volumes) and eluted with MeOH (2 column volumes), the organic solvent removed in vacuo to afford the product as an off-white solid: 1H NMR (400 MHz, DMSO-d6): 12.31 (1H, s), 9.77 (1H, s), 8.85 (1H, d), 8.12 (1H, d), 8.04 (1H, s), 7.94 (1H, s), 7.84 (1H, s), 7.76 (1H, d), 7.39 (1H, t), 7.21 (1H, d), 4.05-3.90 (2H, m). MS: [M+H]+ 379.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:10]2[O:14][C:13]([CH3:16])([CH3:15])[C:12](=[O:17])[C:11]=2[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:5]=[CH:6][C:7]=1[S:8][CH3:9].ClC1C=C(C=CC=1)C(OO)=[O:29].[OH-].[Na+]>ClCCl>[Br:1][C:2]1[CH:3]=[C:4]([C:10]2[O:14][C:13]([CH3:16])([CH3:15])[C:12](=[O:17])[C:11]=2[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:9])=[O:29]
Reactant: CSc1ccc(C2=C(c3ccccc3)C(=O)C(C)(C)O2)cc1Br
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Product: CS(=O)c1ccc(C2=C(c3ccccc3)C(=O)C(C)(C)O2)cc1Br
Reaction time: 0.17 h
Yield: 76.2 %

Procedure:
391 mg of 5-{3-bromo-4-(methylthio)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone (Example 336) dissolved in 50 ml dichloromethane was stirred at 0° C. for 50 minutes in the presence of 183 mg of 70% m-chloroperoxybenzoic acid. Then 10 ml 5% aqueous sodium hydroxide was added to the reaction mixture and the mixed solution was stirred for another 10 minutes. The dichloromethane was removed in vacuo and the resulting residue was extracted with 50 ml water and dichloromethane (30 ml×3). The organic layer was then concentrated under reduced pressure and was purified by column chromatography (hexane/ethylacetate=1:1) to give 310 mg of 5-(3-bromo-4-(methylsulfinyl)phenyl}-2,2-dimethyl-4-phenyl-3(2H)-furanone. NMR: δ1.58 (s, 6H), 2.84 (s, 3H), 7.30 (m, 2H), 7.38 (m, 3H), 7.78 (dd, J=8.4, 1.8 Hz, 1H), 7.88 (d, J=5.4 Hz, 1H), 7.90 (d, J=2.7 Hz, 1H). IR (cm−1): 1698, 1619, 1388, 1064.
Reaction SMILES: [CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH:2]1[C:10]([OH:12])=[O:11].S(=O)(=O)(O)O.[N+:18]([O-])([OH:20])=[O:19]>CCOCC>[N+:18]([C:6]1[CH:5]=[C:4]2[C:9](=[CH:8][CH:7]=1)[CH2:1][CH:2]([C:10]([OH:12])=[O:11])[CH2:3]2)([O-:20])=[O:19]
Reactant: O=[N+]([O-])O
Reactant: O=C(O)C1Cc2ccccc2C1
Agent: O=S(=O)(O)O
Solvent: CCOCC
Product: O=C(O)C1Cc2ccc([N+](=O)[O-])cc2C1
Temperature: 5 °C
Reaction time: 1 h

Procedure:
A solution of indane-2-carboxylic Acid 9a (18.8 g) in ether (250 ml) was added to conc. sulfuric acid (300 ml) (temp.=3-13° C.). To this mixture, a solution of conc. nitric acid (4.4 ml) and conc. sulfuric acid (100 ml) was added (temp.=−1° C.). The mixture was stirred at 2-8° C. for 1 h, poured onto ice, and the aqueous phase was extracted with ether. The combined organic extracts were washed with brine, dried (MgSO4) and evaporated to dryness in vacuo. The residue was crystallized from ether to give 5-nitroindane-2-carboxylic acid (6.0 g). The solid was dissolved in CH2Cl2 (100 ml) and DMF (1 ml). Thionyl chloride (8.4 ml) was added, and the solution was boiled under reflux for 5 hours. Evaporation in vacuo gave the title compound (8.6 g).
Reaction SMILES: [CH3:1][CH:2]([CH3:38])[C@@H:3]([NH:30]C(=O)OC(C)(C)C)[C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]3[NH:18][CH:19]=[C:20]([NH:21][C:22](=[O:29])[C:23]4[CH:28]=[CH:27][CH:26]=[N:25][CH:24]=4)[C:13]=23)[CH2:8][CH2:7]1)=[O:5].C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:30][C@H:3]([CH:2]([CH3:38])[CH3:1])[C:4]([N:6]1[CH2:7][CH2:8][N:9]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]3[NH:18][CH:19]=[C:20]([NH:21][C:22](=[O:29])[C:23]4[CH:28]=[CH:27][CH:26]=[N:25][CH:24]=4)[C:13]=23)[CH2:10][CH2:11]1)=[O:5]
Reactant: CC(C)[C@@H](NC(=O)OC(C)(C)C)C(=O)N1CCN(c2ccnc3[nH]cc(NC(=O)c4cccnc4)c23)CC1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC(C)[C@@H](N)C(=O)N1CCN(c2ccnc3[nH]cc(NC(=O)c4cccnc4)c23)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 79.1 %

Procedure:
(R)-tert-Butyl 3-methyl-1-(4-(3-(nicotinamido)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-1-oxobutan-2-ylcarbamate (0.014 g, 0.027 mmol) was placed in DCM (3 mL) at room temperature. TFA (0.5 mL) was then added, and the reaction was stirred at room temperature for 1 hour. The reaction was then concentrated to dryness. The resulting residue was dissolved in minimal DCM and then added dropwise to a stirring solution of 1M HCl in ether. The resulting solid was filtered, washed with ether, and dried to give (R)—N-(4-(4-(2-amino-3-methylbutanoyl)piperazin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide (0.009 g, 63% yield) as the trihydrochloride salt. MS APCI (+) m/z 422 detected.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][C:5]([N:7]1[CH2:12][CH2:11][N:10]([CH:13]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:9][CH2:8]1)=[O:6].[N-:26]=[N+]=[N-].[Na+].[I-].[K+]>CN(C=O)C>[NH2:26][CH2:2][CH2:3][CH2:4][C:5]([N:7]1[CH2:12][CH2:11][N:10]([CH:13]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:9][CH2:8]1)=[O:6]
Reactant: [N-]=[N+]=[N-]
Reactant: O=C(CCCCl)N1CCN(C(c2ccccc2)c2ccccc2)CC1
Agent: [I-]
Agent: [K+]
Agent: [Na+]
Solvent: CN(C)C=O
Product: NCCCC(=O)N1CCN(C(c2ccccc2)c2ccccc2)CC1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
8.9 g (24.9 mmol) 1-(4-chlorobutyryl)-4-diphenylmethylpiperazine, 4.8 g (73.8 mmol) sodium azide, 1 g potassium iodide and 1 g molecular sieve 4A are stirred in 70 ml DMF for five hours at 70° C. After cooling, the reaction mixture is filtered and the filtrate is concentrated under vacuum. The accumulated crude product is dissolved in methanol and mixed with a spatula tip of palladium-carbon (10%). The mixture is stirred for two days at RT under hydrogen atmosphere. The mixture is filtered from the catalyst and the solvent is removed under vacuum. The residue is chromatographically purified over silica gel with CHCl3/CH3OH/TEA (90/10/5): yield 5.2 g (62%) as a colorless amorphous solid.
Reaction SMILES: [O:1]=[C:2]1[C:6]2([CH2:9][CH2:8][CH2:7]2)[N:5]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)=[CH:12][CH:11]=2)[C:4](=[S:23])[N:3]1[C:24]1[CH:25]=[C:26]([C:32]([F:35])([F:34])[F:33])[C:27]([C:30]#[N:31])=[N:28][CH:29]=1.Br[CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39]>>[C:30]([C:27]1[N:28]=[CH:29][C:24]([N:3]2[C:2](=[O:1])[C:6]3([CH2:9][CH2:8][CH2:7]3)[N:5]([C:10]3[CH:15]=[CH:14][C:13]([O:16][CH:17]4[CH2:22][CH2:21][N:20]([CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH2:19][CH2:18]4)=[CH:12][CH:11]=3)[C:4]2=[S:23])=[CH:25][C:26]=1[C:32]([F:34])([F:33])[F:35])#[N:31]
Reactant: CCOC(=O)CBr
Reactant: N#Cc1ncc(N2C(=O)C3(CCC3)N(c3ccc(OC4CCNCC4)cc3)C2=S)cc1C(F)(F)F
Product: CCOC(=O)CN1CCC(Oc2ccc(N3C(=S)N(c4cnc(C#N)c(C(F)(F)F)c4)C(=O)C34CCC4)cc2)CC1

Procedure:
The title compound was synthesized as described in Example 27 using 5-(8-oxo-5-(4-(piperidin-4-yloxy)phenyl)-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-3-(trifluoromethyl)picolinonitrile and ethyl 2-bromoacetate as starting materials. LCMS [M+1]+ 588.1.
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[C:3]1[CH:8]=[CH:7][N:6]=[C:5]([N:9]2[CH:13]=[C:12]([C:14]([OH:16])=O)[N:11]=[CH:10]2)[CH:4]=1.[NH:19]1[CH2:23][CH2:22][C@H:21]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:20]1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(CC)CC)C>CN(C=O)C>[F:17][C:2]([F:1])([F:18])[C:3]1[CH:8]=[CH:7][N:6]=[C:5]([N:9]2[CH:13]=[C:12]([C:14]([N:19]3[CH2:23][CH2:22][C@H:21]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:29])([CH3:28])[CH3:30])[CH2:20]3)=[O:16])[N:11]=[CH:10]2)[CH:4]=1
Reactant: O=C(O)c1cn(-c2cc(C(F)(F)F)ccn2)cn1
Reactant: CC(C)(C)OC(=O)N[C@H]1CCNC1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N[C@H]1CCN(C(=O)c2cn(-c3cc(C(F)(F)F)ccn3)cn2)C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 1-[4-(trifluoromethyl)pyridin-2-yl]-1H-imidazole-4-carboxylic acid (120 mg, 0.47 mmol) and tert-butyl (3S)-pyrrolidin-3-ylcarbamate (87 mg, 0.47 mmol) in DMF (3 mL) was added benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (210 mg, 0.47 mmol) followed by triethylamine (0.20 mL, 1.4 mmol). The reaction was stirred at room temperature overnight and purified by HPLC to give the title compound. MS (M+H) 426.3.
Reaction SMILES: [OH:1][N:2]1[C:6]([C:7]2[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=2)=[CH:5][CH:4]=[N:3]1.[CH3:15][N:16]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:17](Cl)=[O:18]>>[CH3:14][O:13][C:10]1[CH:9]=[CH:8][C:7]([C:6]2[N:2]([O:1][C:17](=[O:18])[N:16]([CH3:15])[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[N:3]=[CH:4][CH:5]=2)=[CH:12][CH:11]=1
Reactant: CN(C(=O)Cl)c1ccccc1
Reactant: COc1ccc(-c2ccnn2O)cc1
Product: COc1ccc(-c2ccnn2OC(=O)N(C)c2ccccc2)cc1

Procedure:
The title compound was prepared from 1-hydroxy-5-(4-methoxyphenyl)pyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (38%, yellow crystals).
Reaction SMILES: [CH2:1]([S:3]([NH2:6])(=[O:5])=[O:4])[CH3:2].[H-].[Na+].Cl[C:10]1[C:15]([N+:16]([O-:18])=[O:17])=[CH:14][C:13]([C:19]([F:22])([F:21])[F:20])=[CH:12][N:11]=1.O>O1CCCC1>[N+:16]([C:15]1[C:10]([NH:6][S:3]([CH2:1][CH3:2])(=[O:5])=[O:4])=[N:11][CH:12]=[C:13]([C:19]([F:22])([F:20])[F:21])[CH:14]=1)([O-:18])=[O:17]
Reactant: CCS(N)(=O)=O
Reactant: O=[N+]([O-])c1cc(C(F)(F)F)cnc1Cl
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: CCS(=O)(=O)Nc1ncc(C(F)(F)F)cc1[N+](=O)[O-]
Yield: 54.5 %

Procedure:
3.1 g of ethanesulfonamide was dissolved in 50 ml of dry tetrahydrofuran, and 1.2 g of 60% sodium hydride was added thereto under cooling with ice. After completion of the addition, the mixture was reacted for one hour under reflux. After cooling, 5.0 g of 2-chloro-3-nitro-5-trifluoromethylpyridine was added thereto, and then the mixture was reacted for 7 hours under reflux. After completion of the reaction, the reaction product was poured into 200 ml of water. Undissolved materials in water were extracted with ethyl ether and removed. Then, the aqueous layer was weakly acidified with dilute hydrochloric acid. Precipitated crystals were collected by filtration and dried to obtain 3.6 g of N-(3-nitro-5-trifluoromethyl-2-pyridyl)ethanesulfonamide having a melting point of from 160° to 163° C.
Reaction SMILES: Cl[CH2:2][CH2:3][C:4]1[N:8]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[C:22]#[N:23])=[CH:12][CH:11]=2)[C:7]2[C:24]([C:28]([O:30][CH3:31])=[O:29])=[CH:25][CH:26]=[CH:27][C:6]=2[N:5]=1.[C:32]([O-])([O-])=[O:33].[K+].[K+]>CO>[C:22]([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[C:13]1[CH:12]=[CH:11][C:10]([CH2:9][N:8]2[C:7]3[C:24]([C:28]([O:30][CH3:31])=[O:29])=[CH:25][CH:26]=[CH:27][C:6]=3[N:5]=[C:4]2[CH2:3][CH2:2][O:33][CH3:32])=[CH:15][CH:14]=1)#[N:23]
Reactant: COC(=O)c1cccc2nc(CCCl)n(Cc3ccc(-c4ccccc4C#N)cc3)c12
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: COCCc1nc2cccc(C(=O)OC)c2n1Cc1ccc(-c2ccccc2C#N)cc1
Yield: 58.5 %

Procedure:
A mixture of methyl 2-(2-chloroethyl)-1-[(2'-cyanobiphenyl-4-yl)methyl]benzimidazole-7-carboxylate (1.0 g) and K2CO3 (0.25 g) in methanol (30 ml) was refluxed for 2 hours. The reaction mixture was concentrated to dryness to give a residue. The residue was dissolved to dryness to give a residue. The residue filtered off. The filtrate was concentrated to dryness and a resulting syrup was purified by column chromatography on silica gel to give a pale yellow syrup (0.45 g, 59%).
Reaction SMILES: [OH:1][CH2:2][C:3]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH:17]=[N:18][CH3:19])=[C:9]2[C:4]=1[CH:5]=[CH:6][CH:7]=[CH:8]2.[BH4-].[Na+]>C(O)(C)C>[OH:1][CH2:2][C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[C:10]([CH2:17][NH:18][CH3:19])=[C:11]2[C:16]=1[CH:15]=[CH:14][CH:13]=[CH:12]2
Reactant: CN=Cc1c2ccccc2c(CO)c2ccccc12
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(C)O
Product: CNCc1c2ccccc2c(CO)c2ccccc12
Temperature: 25 °C
Reaction time: 72 h
Yield: 84.9 %

Procedure:
10-(hydroxymethyl)-9-((methylimino)methyl)anthracene (1.00 g, 4.0 mmol) was slurried in 25 mL isopropanol. NaBH4 (0.454 g, 12.0 mmol) was added as a solid and the solution was stirred at room temperature for 72 h. The mixture was filtered on a sintered-glass frit and the solvent was removed under reduced pressure to yield 10 as a bright yellow powder (0.853 g, 86% yield): 1H NMR (300.13 MHz, CD3OD) δ 2.55 (s, 3H), 4.64 (s, 2H), 5.56 (s, 2H), 7.55 (m, 4H), 8.38 (m, 2H), 8.50 (m, 2H); 13C-{1H} NMR (75.4 MHz, CD3OD) δ 133.4, 133.0, 131.6, 131.5, 126.9, 126.7, 126.2, 125.7, 57.2, 47.9, 36.5.
Reaction SMILES: [H-].[Na+].[O:3]=[C:4]1[N:8]([C:9]2[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[C:11]([C:17]([F:20])([F:19])[F:18])[CH:10]=2)[C:7](=[O:21])[C:6]2([CH2:26][CH2:25][S:24][CH2:23][CH2:22]2)[NH:5]1>CS(C)=O>[O:3]=[C:4]1[N:8]([C:9]2[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[C:11]([C:17]([F:20])([F:18])[F:19])[CH:10]=2)[C:7](=[O:21])[C:6]2([CH2:26][CH2:25][S:24][CH2:23][CH2:22]2)[N:5]1[CH2:23][CH2:22][CH2:6][CH2:7][OH:21]
Reactant: N#Cc1ccc(N2C(=O)NC3(CCSCC3)C2=O)cc1C(F)(F)F
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Product: N#Cc1ccc(N2C(=O)N(CCCCO)C3(CCSCC3)C2=O)cc1C(F)(F)F
Reaction time: 0.5 h
Yield: 148.5 %

Procedure:
Using the procedure of Example 3, 55 mg of 50% sodium hydride and 355 mg of the product of Example 13 were reacted and 2.5 ml of dimethylsulfoxide were added dropwise over 20 minutes. Rinsing was carried out with 0.5 ml of dimethylsulfoxide and 20 minutes after the release of hydrogen had stopped, 0.41 g of 4-iodo-butoxytrimethylsilane were added. The reaction medium was poured into 25 ml of water containing 0.1 g of monopotassium phosphate and extraction was carried out 3 times with ether. The organic phase was washed with water, then with salt water and dried. The resultant product was taken up in 10 ml of methanol and 1 ml of 2N hydrochloric acid and left for 30 minutes. It was poured into 30 ml of 50% sodium chloride and extraction was carried out 3 times with ethyl acetate. The extracts were washed with salt water and dried. Purification was carried out on silica with methylene chloride-acetone: 9-1 as eluant to obtain 317 mg of the expected product (white crystals) melting at 139°-140° c.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:14]2[C:13]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][C:22](=[O:27])[C:23]([CH2:25]O)=[CH2:24])[CH:16]=3)=[N:12][CH:11]=[N:10][C:9]=2[NH:8][CH:7]=1)=[O:5])[CH3:2].C(Cl)Cl.CCN(S(F)(F)[F:37])CC>CS(C)=O>[CH2:1]([O:3][C:4]([C:6]1[C:14]2[C:13]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][C:22](=[O:27])[C:23]([CH2:25][F:37])=[CH2:24])[CH:16]=3)=[N:12][CH:11]=[N:10][C:9]=2[NH:8][CH:7]=1)=[O:5])[CH3:2]
Reactant: CCN(CC)S(F)(F)F
Reactant: C=C(CO)C(=O)Nc1cccc(-c2ncnc3[nH]cc(C(=O)OCC)c23)c1
Solvent: CS(C)=O
Solvent: ClCCl
Product: C=C(CF)C(=O)Nc1cccc(-c2ncnc3[nH]cc(C(=O)OCC)c23)c1
Temperature: 25 °C

Procedure:
To ethyl-4-(3-{[2-(hydroxymethyl)acryloyl]amino}phenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate (17 mg, 0.045 mmol) was added CH2Cl2 (0.90 mL) and the reaction was cooled to −78° C. before DAST (12 μL, 0.090 mmol) was added. The reaction was allowed to warm to room temperature over 2 hours. The reaction was quenched by pouring into a separatory funnel containing aqueous sodium bicarbonate (saturated) and was extracted with ethyl acetate (×3). The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo to afford a residue that was dissolved in 2 mL of DMSO, and was purified by reverse phase HPLC using an acetonitrile gradient in water with 0.1% TFA modifier. Lyophilization of the desired fractions affords a colorless solid. LRMS (ESI) calc'd for C19H18N4O3F [M+H]+: 369, found 369. 1H NMR (600 MHz, DMSO-D6) δ 13.02 (bs, 1H), 10.25 (s, 114), 8.97 (s, 1H), 8.36 (m, 1H), 8.09 (s, 1H), 7.88 (d, 1H, J=7.8 Hz), 7.47 (t, 1H, J=7.8 Hz), 7.38 (d, 1H, J=7.8 Hz), 6.19 (s, 1H), 5.94 (s, 1H), 5.26 (s, 1H), 5.18 (s, 1H), 3.90 (q, 2H, J=7.2 Hz), 0.90 (t, 3H, J=7.2 Hz).
Reaction SMILES: C(OC([N:11]1[CH2:15][CH2:14][CH:13]([C@@H:16]2[CH2:18][C@@H:17]2[NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:12]1)=O)C1C=CC=CC=1.[H][H]>[Pd].C(O)C>[C:23]([O:22][C:20]([NH:19][C@H:17]1[CH2:18][C@H:16]1[CH:13]1[CH2:14][CH2:15][NH:11][CH2:12]1)=[O:21])([CH3:26])([CH3:24])[CH3:25]
Reactant: [H][H]
Reactant: CC(C)(C)OC(=O)N[C@H]1C[C@H]1C1CCN(C(=O)OCc2ccccc2)C1
Agent: [Pd]
Solvent: CCO
Product: CC(C)(C)OC(=O)N[C@H]1C[C@H]1C1CCNC1

Procedure:
To 15 ml of an ethanol solution of 547.3 mg (1.52 mmol) of 1-benzyloxycarbonyl-3-(cis-2-t-butoxycarbonylaminocyclopropyl)pyrrolidine (isomer A) was added 550 mg of 5% palladium-on-carbon, followed by shaking in a hydrogen stream (4 kg/cm2) for 1.5 hours. The catalyst was removed by filtration, and the solvent was removed by evaporation under reduced pressure to give 343.6 mg (quantitative) of the title compound as a brown oily substance.
Reaction SMILES: Cl[C:2]1[CH:11]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[Cl:18])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([N+:19]([O-:21])=[O:20])[CH:8]=2)[N:3]=1.O.[NH2:23][NH2:24]>>[N+:19]([C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([NH:23][NH2:24])[CH:11]=[C:10]2[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[Cl:18])([O-:21])=[O:20]
Reactant: O=[N+]([O-])c1ccc2nc(Cl)cc(-c3ccccc3Cl)c2c1
Reactant: NN
Solvent: O
Product: NNc1cc(-c2ccccc2Cl)c2cc([N+](=O)[O-])ccc2n1

Procedure:
In the manner given in Example 1, 2-chloro-6-nitro-4-(o-chlorophenyl)quinoline is reacted at reflux with hydrazine hydrate to give 6-nitro-4-(o-chlorophenyl)-2-hydrazinoquinoline
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.Br[CH2:16][CH2:17][CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20].C([O-])([O-])=O.[K+].[K+]>C(#N)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH2:14][CH2:13][N:12]([CH2:16][CH2:17][CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:11][CH2:10]1
Reactant: CCOC(=O)CCCBr
Reactant: COc1ccccc1N1CCNCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCOC(=O)CCCN1CCN(c2ccccc2OC)CC1
Yield: 68.4 %

Procedure:
A stirred mixture of 1-(2-methoxyphenyl)piperazine (1.50 g, 7.8 mmol), ethyl 4-bromobutanoate (0.9 mL, 6.3 mmol), and K2CO3 (0.87 g, 6.3 mmol) in acetonitrile was refluxed overnight. After the mixture was cooled, the mixture was evaporated to dryness and H2O (20 mL) was added to the residue. The aqueous phase was extracted with CH2Cl2 (230 mL). The collected organic layers were dried over Na2SO4 and evaporated under reduced pressure. The crude residue was chromatographed (CHCl3/AcOEt, 1:1, as eluent) to afford pure 13 as a pale yellow oil (1.32 g, 68% yield). 1H NMR: δ 1.24 (t, 3H, J=7.1 Hz, CH2CH3), 1.79-1.89 (m, 2H, CH2CH2CO), 2.34 (t, 2H, J=7.3 Hz, COCH2), 2.41 [t, 2H, J=7.4 Hz, (CH2)2NCH2], 2.63 [br s, 4H, (CH2)2NCH2], 3.06 [br s, 4H, ArN(CH2)2], 3.83 (s, 3H, OCH3), 4.11 (q, 2H, J=7.1 Hz, CH2CH3), 6.82-7.00 (m, 3H, aromatic). GC-MS m/z 307 (M++1, 18), 306 (M+, 77), 261 (32), 205 (100), 190 (37).
Reaction SMILES: [CH2:1]([N:8]1[CH2:14][CH2:13][CH2:12][C:11]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[CH2:22]O)([OH:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.CS(Cl)(=O)=O>O1CCCC1>[CH2:1]([N:8]1[CH2:14][CH2:13][CH2:12][C:11]2([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[CH2:22][O:15]2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: OCc1ccccc1C1(O)CCCN(Cc2ccccc2)CC1
Agent: CS(=O)(=O)Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: c1ccc(CN2CCCC3(CC2)OCc2ccccc23)cc1
Reaction time: 2 h
Yield: 62 %

Procedure:
To a solution of (RS)-1-benzyl-4-(2-hydroxymethyl-phenyl)-azepan-4-ol (7.0 g, 22 mmol) and triethylamine (3.1 ml, 22 mmol) in tetrahydrofuran (80 ml) was added a solution of methanesulfonyl chloride (1.7 ml, 22 mmol) in tetrahydrofuran (20 ml) at 0° C. After completed addition the temperature was allowed to rise to room temperature. Stirring for 2 h was followed by addition of another portion of triethylamine (3.1 ml, 22 mmol). Stirring was continued over night. The reaction mixture was partitioned between water and ethyl acetate. The layers were separated and the organic layer was concentrated in vacuo. Flash column chromatography using heptane/ethyl acetate as eluent gave the title compound as a light yellow oil (4.0 g, 61%).
Reaction SMILES: [C:1]1([NH:7][C:8]2[CH:13]=[CH:12][C:11]([NH2:14])=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[SH:15][CH2:16][CH2:17][C:18](O)=[O:19].C1(C)C(C)=CC=CC=1>CCCCCC>[NH:7]([C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:18](=[O:19])[CH2:17][CH2:16][SH:15])=[CH:10][CH:9]=1)[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=C(O)CCS
Reactant: Nc1ccc(Nc2ccccc2)cc1
Solvent: CCCCCC
Solvent: Cc1ccccc1C
Product: O=C(CCS)Nc1ccc(Nc2ccccc2)cc1
Temperature: 140 °C

Procedure:
A mixture of 18.4 grams of N-phenyl-p-phenylene diamine, 10.6 grams of β-mercaptopropionic acid and 120 milliliters of xylene (technical grade) was heated to reflux (about 140° C.) under nitrogen atmosphere, with stirring. A 1.6 milliliter quantity of water (90% of theory) was removed from this mixture by azeotropic distillation through a Vigreux column with the aid of a Dean-Stark trap, during a 13-hour period. A solid product was isolated in 18.7 grams quantity from the reaction mixture by cooling the latter, pouring into hexane, collecting the resultant crystalline product by filtration, washing the crushed crystalline product with more hexane and evaporating to dryness. The product was recrystallized from hot toluene to 17.6 grams (64.5%) of white platelets melting at 98.3°-99.5° C. The resultant new compound, N-(4-anilino-phenyl)-beta-mercaptopropionamide, sometimes referred to hereafter as MPDA, had merceptan assay of 93.8% of theoretical, on the basis of a potentiometric titration with an isopropyl alcohol solution of silver nitrate, following a method described by R. M. Pierson, A. J. Costanza and A. H. Weinstein, J. Polymer Sci., 17, 234 (1955).