Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][CH:15]=1)[CH2:5][S:6][CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1.[F:16][C:17]([F:25])([F:24])[C:18]([NH:20][CH2:21][C:22]#[CH:23])=[O:19]>>[CH:7]1([S:6][CH2:5][C:4]2[CH:3]=[C:2]([C:23]#[C:22][CH2:21][NH:20][C:18](=[O:19])[C:17]([F:25])([F:24])[F:16])[CH:15]=[CH:14][CH:13]=2)[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1
Reactant: Brc1cccc(CSC2CCCCC2)c1
Reactant: C#CCNC(=O)C(F)(F)F
Product: O=C(NCC#Cc1cccc(CSC2CCCCC2)c1)C(F)(F)F

Procedure:
Sonogashira coupling between (3-bromobenzyl)(cyclohexyl)sulfane and 2,2,2-trifluoro-N-(prop-2-ynyl)acetamide following the method used in Example 139 gave N-(3-(3-(cyclohexylthiomethyl)phenyl)prop-2-ynyl)-2,2,2-trifluoroacetamide as a yellow oil. Yield (0.70 g, 35%); 1H NMR (400 MHz, DMSO-d6) δ 10.0 (br t, 1H), 7.24-7.37 (m, 4H), 4.25 (d, J=5.5 Hz, 2H), 3.72 (s, 2H), 2.48-2.53 (m, 1H), 1.79-1.87 (m, 2H), 1.58-1.65 (m, 2H), 1.45-1.52 (m, 1H), 1.12-1.27 (m, 5H).
Reaction SMILES: C[O:2][C:3]1[C:4]([CH3:33])=[C:5]([C:24]([O:31]C)=[C:25]([O:29][CH3:30])[C:26]=1[O:27][CH3:28])[CH2:6][C:7]1[CH:8]=[CH:9][C:10]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[O:22][CH3:23])=[C:11]([CH:15]=1)[C:12]([OH:14])=[O:13].O=[N+]([O-])[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[Ce+4].[NH4+].[NH4+]>C(#N)C.O>[CH3:28][O:27][C:26]1[C:3](=[O:2])[C:4]([CH3:33])=[C:5]([CH2:6][C:7]2[CH:8]=[CH:9][C:10]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[O:22][CH3:23])=[C:11]([CH:15]=2)[C:12]([OH:14])=[O:13])[C:24](=[O:31])[C:25]=1[O:29][CH3:30]
Reactant: COc1ccccc1-c1ccc(Cc2c(C)c(OC)c(OC)c(OC)c2OC)cc1C(=O)O
Agent: O=[N+]([O-])[O-]
Agent: [Ce+4]
Agent: [NH4+]
Solvent: CC#N
Solvent: O
Product: COC1=C(OC)C(=O)C(Cc2ccc(-c3ccccc3OC)c(C(=O)O)c2)=C(C)C1=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 76 %

Procedure:
5-(3,4,5,6-Tetramethoxy-2-methylbenzyl)-2-(2-methoxyphenyl)benzoic acid (1.21 g, 2.6769 mmol) was dissolved in a mixed solvent of acetonitrile (30 ml) and water (10 ml), then CAN (3.60 g, 6.6914 mmol) was added thereto at room temperature and the mixture was stirred for 3 hour. The reaction solution was poured into water and extracted with ether. The extract was washed with water and dried and the solvent was evaporated therefrom. The residue was purified by silica gel column chromatography (5% methanol-methylene chloride) to give the title compound (859 mg, 2.0355 mmol, 76%).
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[N:11][NH:12][CH:13]=2)[O:3]1.[C:15](#[N:18])[CH:16]=[CH2:17].N12CCCN=C1CCCCC2>C(#N)C>[CH3:1][C:2]1([CH3:14])[C:6]([CH3:7])([CH3:8])[O:5][B:4]([C:9]2[CH:13]=[N:12][N:11]([CH2:17][CH2:16][C:15]#[N:18])[CH:10]=2)[O:3]1
Reactant: CC1(C)OB(c2cn[nH]c2)OC1(C)C
Reactant: C=CC#N
Solvent: C1CCC2=NCCCN2CC1
Solvent: CC#N
Product: CC1(C)OB(c2cnn(CCC#N)c2)OC1(C)C
Reaction time: 2 h

Procedure:
To a solution of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (5.00 g, 25.8 mmol) in acetonitrile (50 mL) was added acrylonitrile (3.4 mL, 52 mmol) followed by 1,8-diazabicyclo[5.4.0]undec-7-ene (1.94 mL, 12.9 mmol). After about 2 hours, the reaction mixture was concentrated under reduced pressure. The crude material was then dissolved in a minimal amount of dichloromethane and purified via silica gel chromatography eluting with a gradient of 10-50% ethyl acetate in heptane to afford the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.03 (s, 1H), 7.64 (s, 1H), 4.40 (t, J=6.4 Hz, 2H), 3.06 (t, J=6.4 Hz, 2H), 1.26 (s, 12H). MS (ESI+) m/z 247.3 (M+H)+.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[N:5][CH:6]=[C:7]([N+:26]([O-])=O)[C:8]=1[N:9]1[CH2:14][CH2:13][CH2:12][C@H:11]([NH:15][C:16](=[O:25])[O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:10]1)#[N:2].[Cl-].[NH4+]>CCO.O.[Fe]>[NH2:26][C:7]1[CH:6]=[N:5][CH:4]=[C:3]([C:1]#[N:2])[C:8]=1[N:9]1[CH2:14][CH2:13][CH2:12][C@H:11]([NH:15][C:16](=[O:25])[O:17][CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:10]1
Reactant: N#Cc1cncc([N+](=O)[O-])c1N1CCC[C@H](NC(=O)OCc2ccccc2)C1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CCO
Product: N#Cc1cncc(N)c1N1CCC[C@H](NC(=O)OCc2ccccc2)C1
Temperature: 85 °C
Reaction time: 0.25 h
Yield: 92.1 %

Procedure:
A mixture of benzyl [(3S)-1-(3-cyano-5-nitropyridin-4-yl)piperidin-3-yl]carbamate (0.065 g, 0.17 mmol), iron (0.084 g, 1.5 mmol), and ammonium chloride (0.091 g, 1.7 mmol) in EtOH (2 mL) and water (0.2 mL) was stirred at 85° C. for 15 min. The crude reaction mixture was filtered through a pad of diatomaceous earth and the inorganics were washed thoroughly with EtOH. The filtrate was concentrated under reduced pressure and the residue was partitioned between water and EtOAc. The organic fraction was washed with water, brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to afford the sub-title compound (0.055 g). LCMS (ESI) calc. for C19H22N5O2 m/z=352.2 [M+H]+. found 352.1.
Reaction SMILES: [O:1]1[CH:7]2[CH:2]1[C:3](OC)([O:19]C)[C:4]([NH:9][C:10](=[O:18])[C:11]1[C:12](=[CH:14][CH:15]=[CH:16][CH:17]=1)[OH:13])=[CH:5][C:6]2=[O:8].C(OCC)(=O)C>C(Cl)Cl>[O:1]1[CH:2]2[CH:7]1[C:6](=[O:8])[CH:5]=[C:4]([NH:9][C:10](=[O:18])[C:11]1[C:12](=[CH:14][CH:15]=[CH:16][CH:17]=1)[OH:13])[C:3]2=[O:19]
Reactant: COC1(OC)C(NC(=O)c2ccccc2O)=CC(=O)C2OC21
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: O=C(NC1=CC(=O)C2OC2C1=O)c1ccccc1O
Yield: 47.1 %

Procedure:
5,6-Epoxy-4,4-dimethoxy-3-salicyloylamino-2-cyclohexenone (1.0 g, 3.27 mmol) was dissolved in methylene chloride (25 ml), trifluoroboron diethyl ether complex (1 ml) was added thereto under ice cooling, and the mixture was stirred at the same temperature as described above for 30 minutes. Ethyl acetate (300 ml) was added to the reaction mixture and the reaction mixture was washed with water (200 ml). After drying it over Glauber's salt, the ethyl acetate layer was dried under vacuum to obtain brown solids, which were washed with methanol (5 ml) to obtain the titled compound (399 mg) as pale brown solids (yield: 47%).
Reaction SMILES: [F:1][C:2]1[CH:28]=[CH:27][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][N:17]4[CH:25]([OH:26])[C:24]5[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=5)[CH2:18]4)[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.FC(F)(F)C(O)=O.C([SiH](CC)CC)C.C([O-])(O)=O.[Na+]>ClCCl>[F:1][C:2]1[CH:28]=[CH:27][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][N:17]4[CH2:18][C:19]5[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=5)[C:25]4=[O:26])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1
Reactant: OC1c2ccccc2CN1CCN1CCC(c2noc3cc(F)ccc23)CC1
Agent: CC[SiH](CC)CC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C1c2ccccc2CN1CCN1CCC(c2noc3cc(F)ccc23)CC1
Reaction time: 18 h
Yield: 79 %

Procedure:
To 2-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-2,3-dihydro-3-hydroxy-1H-isoindol! -1-one (2.2 g, 5.6 mmol) was added a solution of trifluoroacetic acid (11.0 ml) in dichloromethane (30 ml) at room temperature, under nitrogen. Triethylsilane (1.5 ml) was then added and the reaction mixture was allowed to stir for 18 hours at which time it was poured into a NaHCO3 (sat.). The layers were separated and the aqueous phase was extracted with DCM (3×). The combined organics were washed with brine and dried (Na2SO4). Filtration and concentration gave the crude product as a solid which was recrystallized from EtOAc to give 1.6 g (79%) of the desired product as a white solid, m.p.=166°-168° C.
Reaction SMILES: [NH:1]1[CH2:11][CH2:10][CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH2:3][CH2:2]1.[CH3:12][C:13]([CH3:15])=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>ClCCCl>[CH3:12][CH:13]([N:1]1[CH2:2][CH2:3][CH:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH2:10][CH2:11]1)[CH3:15]
Reactant: CCOC(=O)C1CCNCC1
Reactant: CC(C)=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCCl
Product: CCOC(=O)C1CCN(C(C)C)CC1
Temperature: 25 °C
Reaction time: 72 h
Yield: 93.3 %

Procedure:
Ethyl isonipecotate (3.2 g, 20 mmol, 1 eq) was combined with acetone (5.8 g, 100 mmol, 5 eq), sodium triacetoxyborohydride (10.5 g, 50 mmol, 2.5 eq) and 1,2-dichloroethane (200 mL). The reaction mixture was stirred at rt for 72 h. Saturated aqueous NaHCO3 was added, and the mixture was extracted with CH2Cl2. The organic extracts were dried, filtered through a silica gel pad, and concentrated in vacuo to provide 3.72 g (93%) of ethyl 1-(1-methylethyl)-4-piperidine carboxylate as a colorless liquid.
Reaction SMILES: [CH2:1]([C:6]1[N:11]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:9]=[CH:8][N:7]=1)[CH2:2][CH2:3][CH:4]=C.[OH2:16]>C1COCC1.O.O=[Os](=O)(=O)=O>[F:13][C:12]([F:15])([F:14])[C:10]1[CH:9]=[CH:8][N:7]=[C:6]([CH2:1][CH2:2][CH2:3][CH:4]=[O:16])[N:11]=1
Reactant: C=CCCCc1nccc(C(F)(F)F)n1
Reactant: O
Agent: O=[Os](=O)(=O)=O
Solvent: C1CCOC1
Product: O=CCCCc1nccc(C(F)(F)F)n1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of 2-(4-penten-1-yl)-4-(trifluoromethyl)pyrimidine (P7, 143 mg) in THF/H2O 5/1 (6.5 mL) were added OsO4 (4% in water, 0.2 mL) and NaIO4 (424 mg). The solution was stirred at r.t. for 30 min. Water was then added and the mixture extracted with DCM. The organic phase was washed with brine, dried over Na2SO4, filtered and evaporated in vacuo to give 91 mg of the title compound as an oil, which was used in the subsequent step without further purification.
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][C@H:2]1[C:6]([OH:8])=[O:7].O.C([O-])([O-])=O.[Na+].[Na+].[CH:16]1[CH:21]=[CH:20][C:19]([CH2:22][O:23][C:24](Cl)=[O:25])=[CH:18][CH:17]=1>C1COCC1>[CH2:22]([O:23][C:24]([N:1]1[CH2:5][CH2:4][CH2:3][C@H:2]1[C:6]([OH:8])=[O:7])=[O:25])[C:19]1[CH:20]=[CH:21][CH:16]=[CH:17][CH:18]=1
Reactant: O=C(O)[C@@H]1CCCN1
Reactant: O=C(Cl)OCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)[C@@H]1CCCN1C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 69.2 %

Procedure:
To a stirred solution of (S)-pyrrolidine-2-carboxylic acid (7) (2.0 g, 17.39 mmol) in THF:H2O (20 mL, 1:1) were added Na2CO3 (2.76 g, 26.08 mmol) and Cbz-Cl (3.54 g, 20.80 mmol) and stirred at RT for 18 h. The reaction mixture was washed with EtOAc (10 mL) and the aqueous layer was acidified with 3N HCl and extracted with EtOAc (2×20 mL). The combined organic layer was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure to yield compound 8 (3.0 g, 69.7%).
Reaction SMILES: [CH:1]([NH:4][CH2:5][C:6]1[CH:7]=[C:8]([CH:11]=[CH:12][CH:13]=1)[C:9]#[N:10])([CH3:3])[CH3:2].[C:14]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])(=[O:17])[CH:15]=[CH2:16].C1CCN2C(=NCCC2)CC1>O>[C:9]([C:8]1[CH:7]=[C:6]([CH:13]=[CH:12][CH:11]=1)[CH2:5][N:4]([CH:1]([CH3:3])[CH3:2])[CH2:16][CH2:15][C:14]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])#[N:10]
Reactant: C=CC(=O)OC(C)(C)C
Reactant: CC(C)NCc1cccc(C#N)c1
Solvent: C1CCC2=NCCCN2CC1
Solvent: O
Product: CC(C)N(CCC(=O)OC(C)(C)C)Cc1cccc(C#N)c1
Temperature: 80 °C

Procedure:
A mixture of 3-[(isopropylamino)methyl]benzonitrile (5.7 g, 32.7 mmol), tert-butyl acrylate (4.78 ml, 32.7 mmol) and DBU (5.0 ml, 32.7 mmol) was heated neat at 80° C. for 24 hours. The reaction mixture was diluted with water and extracted with DCM. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. After purification by chromatography (silica, pet ether/EtOAc), the title compound was obtained as a colorless oil. 1H NMR (DMSO-d6, 400 MHz) δ 7.73 (s, 1H), 7.67 (d, J=7.7 Hz, 1H), 7.63 (d, J=7.8 Hz, 1H), 7.49 (t, J=7.7 Hz, 1H), 3.56 (s, 2H), 2.75 (m, 1H), 2.62 (t, J=6.5 Hz, 2H), 2.25 (t, J=6.4 Hz, 2H), 1.39 (s, 9H), 0.83 (d, J=8.8 Hz, 6H).
Reaction SMILES: [O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([C:11]3[CH:12]=[C:13]4[CH:19]=[CH:18][NH:17][C:14]4=[N:15][CH:16]=3)[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[OH-].[K+].[I:22]I>CN(C=O)C>[I:22][C:19]1[C:13]2[C:14](=[N:15][CH:16]=[C:11]([CH:8]3[CH2:7][CH2:6][C:5]4([O:4][CH2:3][CH2:2][O:1]4)[CH2:10][CH2:9]3)[CH:12]=2)[NH:17][CH:18]=1
Reactant: c1cc2cc(C3CCC4(CC3)OCCO4)cnc2[nH]1
Reactant: II
Agent: [K+]
Agent: [OH-]
Solvent: CN(C)C=O
Product: Ic1c[nH]c2ncc(C3CCC4(CC3)OCCO4)cc12
Temperature: 25 °C
Reaction time: 3.5 h

Procedure:
To a stirred solution of the azaindole (XIb-19) (2.51 g, 9.72 mmol) in DMF (40 mL), was added crushed KOH pellets (2.05 g, 36.6 mmol) followed by I2 (2.22 g, 8.7 mmol). The mixture was stirred at room temperature for 3.5 h and concentrated in vacuum. The residue was partitioned between EtOAc (100 mL) and saturated aqueous NaHCO3 solution (40 mL). The aqueous layer was extracted with EtOAc (3×60 mL). The combined organic solutions were dried (MgSO4), filtered and concentrated. The residue consisting of crude iodide (XIIb-19) was used for the preparation of (IXb-19) without any additional purification.
Reaction SMILES: Cl[C:2]1[N:7]2[N:8]=[CH:9][C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:6]2[N:5]=[CH:4][C:3]=1[C:16]([O:18][CH3:19])=[O:17].[F:20][C:21]1[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][C:22]=1[NH2:23]>>[CH2:14]([O:13][C:11]([C:10]1[CH:9]=[N:8][N:7]2[C:2]([NH:23][C:22]3[CH:24]=[C:25]([CH3:28])[CH:26]=[CH:27][C:21]=3[F:20])=[C:3]([C:16]([O:18][CH3:19])=[O:17])[CH:4]=[N:5][C:6]=12)=[O:12])[CH3:15]
Reactant: Cc1ccc(F)c(N)c1
Reactant: CCOC(=O)c1cnn2c(Cl)c(C(=O)OC)cnc12
Product: CCOC(=O)c1cnn2c(Nc3cc(C)ccc3F)c(C(=O)OC)cnc12
Yield: 47 %

Procedure:
In the same manner as in Example 1, step 4 and using methyl 7-chloro-3-ethoxycarbonylpyrazolo[1,5-a]pyrimidine-6-carboxylate (4.0 g, 14.0 mmol) obtained in Example 21, step 2 and 2-fluoro-5-methylaniline (2.4 mL, 20.9 mmol), the title compound (2.45 g, 47%) was obtained.
Reaction SMILES: [F:1][C:2]([F:28])([F:27])[C:3]1[CH:4]=[C:5]([CH2:9][N:10]2[C:22]3[CH:21]=[CH:20][CH:19]=[C:18]([OH:23])[C:17]=3[C:16]3[C:11]2=[CH:12][CH:13]=[CH:14][C:15]=3[C:24](=[O:26])[NH2:25])[CH:6]=[CH:7][CH:8]=1.Br[CH2:30][C:31]([O:33][CH3:34])=[O:32]>CN(C=O)C.C(OCC)(=O)C>[F:28][C:2]([F:27])([F:1])[C:3]1[CH:4]=[C:5]([CH2:9][N:10]2[C:22]3[CH:21]=[CH:20][CH:19]=[C:18]([O:23][CH2:30][C:31]([O:33][CH3:34])=[O:32])[C:17]=3[C:16]3[C:11]2=[CH:12][CH:13]=[CH:14][C:15]=3[C:24](=[O:26])[NH2:25])[CH:6]=[CH:7][CH:8]=1
Reactant: COC(=O)CBr
Reactant: NC(=O)c1cccc2c1c1c(O)cccc1n2Cc1cccc(C(F)(F)F)c1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COC(=O)COc1cccc2c1c1c(C(N)=O)cccc1n2Cc1cccc(C(F)(F)F)c1
Reaction time: 0.25 h
Yield: 87.9 %

Procedure:
40% Methanolic Triton B (0.18 mL, 0.4 mM) was added to a solution of the 9-[(3-trifluoromethylphenyl)methyl]-4-hydroxy-5-carbamoyl carbazole (115 mg, 0.3 mN) in 5 mL DMF at room temperature. After 15 minutes, methyl bromoacetate (95 mg, 0.6 mM) was added and the resultant mixture stirred at room temperature for 22 hours. The mixture was diluted with ethyl acetate, washed four times with H2O, 1 N HCl, H2O, sat. NaHCO3, and saturated brine, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by column chromatography on silica gel (elution with ethyl acetate) to afford 120 mg (88%) of the {9-[(3-trifluoromethylphenyl)methyl]-5-carbamoylcarbazol-4-yl}oxyacetic acid, methyl ester as a white solid. 1H NMR (CDCl3) δ7.5-7.2 (m, 7H), 7.1 (d, 1H, J=8 Hz), 7.0 (d, 1H, J=8 Hz), 6.6 (d, 1H, J=8 Hz), 6.4 (br s, 1H), 6.0 (br s, 1H), 5.55 (s, 2H), 4.9 (s, 2H), and 3.9 (s, 3H). IR (KBr, cm−1) 1763 and 1673. MS (ES) m/e 457.
Reaction SMILES: [CH3:1][S:2][C:3]1[S:7][C:6]([N:8]=[C:9]=[O:10])=[N:5][N:4]=1.[CH2:11]([NH:14][CH2:15][CH:16]=[O:17])[CH2:12][CH3:13]>C1C=CC=CC=1>[CH2:11]([N:14]([CH2:15][CH:16]=[O:17])[C:9]([NH:8][C:6]1[S:7][C:3]([S:2][CH3:1])=[N:4][N:5]=1)=[O:10])[CH2:12][CH3:13]
Reactant: CCCNCC=O
Reactant: CSc1nnc(N=C=O)s1
Solvent: c1ccccc1
Product: CCCN(CC=O)C(=O)Nc1nnc(SC)s1

Procedure:
A mixture of 5-methylthio-1,3,4-thiadiazol-2-yl isocyanate dimer (0.05 mole), the dimethyl acetal of 2-propylaminoacetaldehyde (0.1 mole) and benzene (60 ml) are charged into a glass reaction vessel equipped with a mechanical stirrer and reflux condenser. The reaction mixture is heated at reflux for a period of about 15 minutes. After this time the mixture is stripped of benzene under reduced pressure to yield a solid product as the residue. The residue is then recrystallized to yield the desired product the dimethyl acetal of 2-[1-propyl-3-(5-methylthio-1,3,4-thiadiazol-2-yl)ureido] acetaldehyde.
Reaction SMILES: [CH3:1][O:2][C@H:3]1[CH2:20][CH2:19][C@@:18]2([CH3:21])[C:5](=[CH:6][C:7](=[O:23])[C@@H:8]3[C@@H:17]2[CH2:16][CH2:15][C@@:13]2([CH3:14])[C@H:9]3[CH2:10][CH2:11][C:12]2=[O:22])[CH2:4]1.[BH4-].[Na+]>C(Cl)Cl.CO>[CH3:1][O:2][C@H:3]1[CH2:20][CH2:19][C@@:18]2([CH3:21])[C:5](=[CH:6][C@H:7]([OH:23])[C@@H:8]3[C@@H:17]2[CH2:16][CH2:15][C@@:13]2([CH3:14])[C@H:9]3[CH2:10][CH2:11][C@@H:12]2[OH:22])[CH2:4]1
Reactant: CO[C@H]1CC[C@@]2(C)C(=CC(=O)[C@@H]3[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]32)C1
Agent: [BH4-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CO
Product: CO[C@H]1CC[C@@]2(C)C(=C[C@H](O)[C@H]3[C@@H]4CC[C@H](O)[C@@]4(C)CC[C@@H]32)C1

Procedure:
24 was prepared by reduction of 3β-methoxyandrost-5-ene-7,17-dione 20, with sodium borohydride in a mixture of methylene dichloride-methanol at room temperature. The product was purified by column chromatography.
Reaction SMILES: [NH2:1][CH2:2][C@H:3]1[CH2:8][CH2:7][C@H:6]([C:9]([OH:11])=[O:10])[CH2:5][CH2:4]1.[F:12][C:13]([F:33])([F:32])[CH2:14][O:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][C:24]([F:27])([F:26])[F:25])=[CH:18][C:17]=1[S:28](Cl)(=[O:30])=[O:29]>C1COCC1.[OH-].[Na+]>[F:33][C:13]([F:12])([F:32])[CH2:14][O:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][C:24]([F:25])([F:26])[F:27])=[CH:18][C:17]=1[S:28]([NH:1][CH2:2][C@H:3]1[CH2:4][CH2:5][C@H:6]([C:9]([OH:11])=[O:10])[CH2:7][CH2:8]1)(=[O:30])=[O:29]
Reactant: O=S(=O)(Cl)c1cc(OCC(F)(F)F)ccc1OCC(F)(F)F
Reactant: NC[C@H]1CC[C@H](C(=O)O)CC1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: O=C(O)[C@H]1CC[C@H](CNS(=O)(=O)c2cc(OCC(F)(F)F)ccc2OCC(F)(F)F)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of trans-4-aminomethyl-cyclohexanecarboxylic acid (1.5 g, 10 mmol) in THF (10 mL) and 1 M aqueous sodium hydroxide (27 mL) was added a solution of 2,5-bis(2,2,2-trifluoroethoxy)benzenesulfonyl chloride (3.8 g, 10.25 mmol) in THF (10 mL) dropwise and the mixture was stirred at ambient temperature for 2 hr. The resulting mixture was concentrated and 1 M aqueous HCl (22.5 mL) was added. The resulting precipitate was filtered, washed with water and hexanes to give trans-4-{[2,5-bis-(2,2,2-trifluoro-ethoxy)-benzenesulfonylamino]-methyl}-cyclohexanecarboxylic acid as a white powder (2.8 g, 57%).
Reaction SMILES: [CH:1]1([NH:6][C:7]2[CH:12]=[CH:11][N:10]3[N:13]=[C:14]([C:23]4[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=4)[C:15]([C:16](=O)[CH:17]=[CH:18]N(C)C)=[C:9]3[CH:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.[CH:32]1([NH:37][C:38]([NH2:40])=[NH:39])[CH2:36][CH2:35][CH2:34][CH2:33]1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[CH:1]1([NH:6][C:7]2[CH:12]=[CH:11][N:10]3[N:13]=[C:14]([C:23]4[CH:24]=[CH:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=4)[C:15]([C:16]4[CH:17]=[CH:18][N:40]=[C:38]([NH:37][CH:32]5[CH2:36][CH2:35][CH2:34][CH2:33]5)[N:39]=4)=[C:9]3[CH:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: N=C(N)NC1CCCC1
Reactant: COc1ccc(-c2nn3ccc(NC4CCCC4)cc3c2C(=O)C=CN(C)C)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc(-c2nn3ccc(NC4CCCC4)cc3c2-c2ccnc(NC3CCCC3)n2)cc1
Temperature: 25 °C
Yield: 87 %

Procedure:
To a solution of 1-[5-(cyclopentylamino)-2-(4-methoxyphenyl)pyrazolo[1,5-α]pyridin-3-yl]-3-(dimethylamino)-2-propen-1-one (1.05 g, 2.60 mmol) in N,N-dimethylformamide (20 mL) was added N-cyclopentyl guanidine hydrochloride (1.27 g, 7.79 mmol; Prepared by modification of a procedure from Bannard, R. A. B. et al., Can. J. Chem. 1958, 36,1541–1549), followed by potassium carbonate (0.54 g, 3.89 mmol). The resulting solution was heated at reflux for 15 hours. Upon cooling to room temperature, water was added. The mixture was extracted with ethyl acetate. The ethyl acetate phase was washed with brine, dried (magnesium sulfate), filtered and concentrated in vacuo. The resulting residue was purified by flash chromatography (4:6 ethyl acetate:hexane) to give N-cyclopentyl-3-[2-(cyclopentylamino)-4-pyrimidinyl]-2-(4-methoxyphenyl)-pyrazolo[1,5-α]pyridin-5-amine (1.06 g, 87%) as a yellow solid. 1H NMR (CDCl3): δ 8.15 (d, 1H), 7.91 (d, 1H), 7.51 (d, 2H), 7.41 (d, 1H), 6.94 (d, 2H), 6.26 (d, 1H), 6.22 (dd, 1H). 5.11 (d, 1H), 4.42 (m, 1H), 4.09 (d, 1H), 3.88 (m, 1H), 3.85 (s, 3H), 2.10–2.01 (m, 4H), 1.76–1.52 (m, 12H); MS m/z 469 (M+1).
Reaction SMILES: Cl[CH2:2][C:3]1[C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[C:11]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)[C:10]2[C:5](=[CH:6][C:7]([O:27][CH3:28])=[C:8]([O:25][CH3:26])[CH:9]=2)[N:4]=1.[CH2:29]([NH:31][CH2:32][CH3:33])[CH3:30]>>[Cl:24][C:21]1[CH:20]=[CH:19][C:18]([C:11]2[C:10]3[C:5](=[CH:6][C:7]([O:27][CH3:28])=[C:8]([O:25][CH3:26])[CH:9]=3)[N:4]=[C:3]([CH2:2][N:31]([CH2:32][CH3:33])[CH2:29][CH3:30])[C:12]=2[C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:23][CH:22]=1
Reactant: CCNCC
Reactant: CCOC(=O)c1c(CCl)nc2cc(OC)c(OC)cc2c1-c1ccc(Cl)cc1
Product: CCOC(=O)c1c(CN(CC)CC)nc2cc(OC)c(OC)cc2c1-c1ccc(Cl)cc1

Procedure:
According to the same manner as that described in Example 33, ethyl 2-chloromethyl-4-(4-chlorophenyl)-6,7-dimethoxyquinoline-3-carboxylate was reacted with diethylamine to give ethyl 4-(4-chlorophenyl)-2-(N,N-diethylaminomethyl)-6,7-dimethoxyquinoline-3-carboxylate. This compound was recrystallized from ethyl acetate - hexane. Colorless prisms, mp. 82°-83° C.
Reaction SMILES: [C:1]1([CH2:7][O:8][C:9](=[O:15])[NH:10][CH2:11][CH2:12][CH2:13][NH2:14])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)C(C)C)(C)C.Br[CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28]>CN(C)C=O>[C:1]1([CH2:7][O:8][C:9](=[O:15])[NH:10][CH2:11][CH2:12][CH2:13][NH:14][CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: NCCCNC(=O)OCc1ccccc1
Reactant: CC(C)(C)OC(=O)CBr
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)CNCCCNC(=O)OCc1ccccc1
Reaction time: 8 h

Procedure:
A solution of (3-aminopropyl)carbamic acid phenylmethyl ester (7.08 g, 34 mmol) and N,N-diisopropylethylamine (4.5 mL, 26 mmol) in anhydrous dimethylformamide (100 mL) under nitrogen was cooled to 10° C. and treated with t-butyl bromoacetate (2.80 mL, 17 mmol) over 5 minutes. After one hour the bath was removed and the reaction mixture was stirred overnight, poured into water (500 mL), and made basic (pH 12) with 2.5N sodium hydroxide solution. The aqueous layer was extracted with dichloromethane (2×250 mL), which was dried over sodium sulfate and concentrated in vacuo with heat to remove dimethylformamide. The residue was purified by flash chromatography (9 cm diameter, gradient elution with 2.5-3.5% methanol in dichloromethane) to yield [3-[[(1,1-dimethylethyloxycarbonyl)-methyl]amino]propyl]carbamic acid phenylmethyl ester as a pale yellow oil (4.50 g 82%); 1H NMR (CDCl3 200 MHz): δ 7.35 (m, 5H), 5.43 (br s, NH), 5.09 (s, 2H), 3.35-3.24 (m, 4H), 2.68 (t, J=6.5 Hz, 2H), 1.68 (p, J=6.5 Hz, 2H), 1.46 (s, 9H).