Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6](=[O:18])[CH2:7][CH:8]([OH:17])[C:9]1[CH:14]=[CH:13][N:12]=[C:11]([S:15][CH3:16])[N:10]=1)([CH3:4])([CH3:3])[CH3:2].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.O.[O-]S(S([O-])=O)=O.[Na+].[Na+]>C(Cl)Cl>[C:1]([O:5][C:6](=[O:18])[CH2:7][C:8]([C:9]1[CH:14]=[CH:13][N:12]=[C:11]([S:15][CH3:16])[N:10]=1)=[O:17])([CH3:3])([CH3:4])[CH3:2]
Reactant: CSc1nccc(C(O)CC(=O)OC(C)(C)C)n1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: CSc1nccc(C(=O)CC(=O)OC(C)(C)C)n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 95 %

Procedure:
To a solution of 3-hydroxy-3-(2-methylsulfanyl-pyrimidin-4-yl)-propionic acid tert-butyl ester, 18, (5.6 g, 20.9 mmol) in CH2Cl2 is added Dess-Martin periodinane (10.7 g, 25.1 mmol) followed by H2O (0.5 mL, 25.1 mmol). After stirring 1 h at room temperature, the solution is poured into aqueous saturated Na2S2O4. The aqueous phase is extracted with CH2Cl2, then EtOAc. The combined organic phases are dried (MgSO4), filtered and concentrated in vacuo. The crude residue is purified over silica (10% EtOAc/hexanes) to afford 5.6 g (95% yield) of the desired product. 1H NMR (300 MHz, CDCl3) (observed 3:1 mixture of enol:keto tautomers) enol tautomer: δ 12.34 (s, OH), 8.67 (d, J=5.1 Hz, 1H), 7.48 (d, J=5.1 Hz, 1H), 6.35 (s, 1H), 2.62 (s, 3H), 1.57 (s, 9H); ESI+ MS: m/z (rel intensity) 269.1 (30, M++H).
Reaction SMILES: [BH4-].[Na+].[CH2:3]([O:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:27][CH3:28])=[CH:24][CH:25]=3)[CH2:20][CH2:19][N:18]=2)=[CH:13][CH:12]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1>CO>[CH2:3]([O:10][C:11]1[CH:12]=[CH:13][C:14]([CH:17]2[C:26]3[C:21](=[CH:22][C:23]([O:27][CH3:28])=[CH:24][CH:25]=3)[CH2:20][CH2:19][NH:18]2)=[CH:15][CH:16]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: COc1ccc2c(c1)CCN=C2c1ccc(OCc2ccccc2)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: COc1ccc2c(c1)CCNC2c1ccc(OCc2ccccc2)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 72.4 %

Procedure:
Sodium borohydride (10.874 g, 287.3 mmol) was added in small portions to a solution of 1-(4-benzyloxyphenyl)-6-methoxy-3,4-dihydroisoquinoline (54.56 g, 143.6 mmol) in MeOH (600 ml) at 0° C. The reaction mixture was stirred at 0° C. for 1 hr, then quenched by the dropwise addition of H2O (20 ml). The resulting mixture was concentrated in vacuo to a volume of about 100 ml. The solid that separated was collected to give 35.926 g (72% yield) of white solid.
Reaction SMILES: [C:1]([O:5][O:6][C:7](=[O:22])[C:8]1[CH:13]=[CH:12][C:11]([C:14](=[O:21])[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:10][CH:9]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:23][O:24]C1C=CC(C(C2C=CC(C(O)=O)=CC=2)=O)=CC=1>CCOCC.ClCCl>[C:1]([O:5][O:6][C:7](=[O:22])[C:8]1[CH:13]=[CH:12][C:11]([C:14](=[O:21])[C:15]2[CH:20]=[CH:19][C:18]([O:24][CH3:23])=[CH:17][CH:16]=2)=[CH:10][CH:9]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: COc1ccc(C(=O)c2ccc(C(=O)O)cc2)cc1
Reactant: CC(C)(C)OOC(=O)c1ccc(C(=O)c2ccccc2)cc1
Solvent: CCOCC
Solvent: ClCCl
Product: COc1ccc(C(=O)c2ccc(C(=O)OOC(C)(C)C)cc2)cc1

Procedure:
Tert-butyl-4-(4'-methoxybenzoyl)perbenzoate is prepared by the above discussed procedure for the preparation of t-butyl-4-benzoylperbenzoate, except that the acid employed is 4-(4'-methoxybenzoyl)-benzoic acid, and during the preparation, the corresponding acid chloride is dissolved in a mixture of ether and dichloromethane.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].Cl.[NH2:11]C1C=CC=CC=1.N([O-])=O.[Na+].[OH-].[Na+]>O.Cl>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][NH2:11])[CH:6]=[CH:7][C:8]=1[F:9]
Reactant: Nc1ccccc1
Reactant: Nc1ccc(F)c(Cl)c1
Agent: Cl
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Product: NNc1ccc(F)c(Cl)c1
Temperature: 80 °C
Reaction time: 24 h
Yield: 67 %

Procedure:
A mixture of 144.9 g of 3-chloro-4-fluoroaniline and 705 ml of concentrated hydrochloric acid was stirred and heated to 80° C. The mixture containing the aniline hydrochloride was allowed to cool to ambient temperature. After 24 hours, the mixture was stirred and cooled to 5°-10° C. while a solution of 69.5 g of sodium nitrite in 350 ml of water was added dropwise within 1/2 hour. After an additional 1/2 hour, the solution containing the diazonium salt was gradually added with stirring to a solution of 427 g of stannous chloride (2H2O) in 700 ml of hydrochloric acid. After 45 minutes at ambient temperature, the reaction mixture was made alkaline by the addition of 3000 ml of 50% sodium hydroxide and extracted with ether. The combined ether extracts were dried (MgSO4), filtered and concentrated to give 214.1 g (67%) of 3-chloro-4-fluorophenylhydrazine as a tan solid; melting point 75°-77° C.
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[CH2:6]([O:13][CH2:14][C:15]1([CH2:18][OH:19])[CH2:17][CH2:16]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C(N(CC)CC)C>ClCCl>[CH3:1][S:2]([O:19][CH2:18][C:15]1([CH2:14][O:13][CH2:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[CH2:16][CH2:17]1)(=[O:4])=[O:3]
Reactant: OCC1(COCc2ccccc2)CC1
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)OCC1(COCc2ccccc2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 77.6 %

Procedure:
Methane sulfonyl chloride (5.2 mL, 68.7 mmol) was added drop wise to an ice cooled solution of {1-[(benzyloxy)methyl]cyclopropyl}methanol (Compound 63E, 11 g, 57.2 mmol) and triethylamine (15.5 mL, 114 mmol) in dichloromethane (50 mL). The reaction mixture warmed to RT and allowed to stir overnight. The reaction mixture was filtered to remove solids. The filtrate was washed with saturated sodium bicarbonate solution followed by brine, dried over magnesium sulfate, filtered and concentrated to give 12 g (77%) of the desired product as light yellow oil which was used without further purification. 1H NMR (400 MHz, CDCl3) δ 7.25-7.41 (m, 5H), 4.58 (s, 2H), 4.21 (s, 2H), 3.42 (s, 2H), 2.96 (s, 3H), 0.61-0.75 (m, 4H).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1([C:14]([OH:16])=[O:15])[CH2:13][CH2:12][CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:17](=O)([O-])[O-].[K+].[K+].IC>CC(C)=O>[CH3:17][O:15][C:14]([C:9]1([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:13][CH2:12][CH2:11][CH2:10]1)=[O:16]
Reactant: CC(C)(C)OC(=O)NC1(C(=O)O)CCCC1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CC(C)=O
Product: COC(=O)C1(NC(=O)OC(C)(C)C)CCCC1
Temperature: 25 °C
Yield: 103.7 %

Procedure:
In a 150 mL round-bottomed flask 1-tert-butoxycarbonylamino-cyclopentanecarboxylic acid (1.00 g, 4.36 mmol) was dissolved in acetone (30 mL). Potassium carbonate (1.51 g, 10.9 mmol) was added followed by iodomethane (0.41 mL, 6.54 mmol). The reaction mixture was heated at reflux overnight then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the residue was partitioned between diethyl ether and H2O. The aqueous layer was extracted with diethyl ether. The combined organics were washed with H2O and brine then dried over Na2SO4, filtered and concentrated to afford 1.1 g (99%) of 1-tert-butoxycarbonylamino-cyclopentanecarboxylic acid methyl ester as a white solid.
Reaction SMILES: BrC1C=CC=C2C=1C(C1C(O)=CC3OCOC=3C=1)[C:5](=[O:16])N2CCCCC.[Br:27][C:28]1[CH:36]=[CH:35][CH:34]=[C:33]2[C:29]=1[CH:30]([C:44]1[CH:49]=[C:48]([F:50])[C:47]([F:51])=[CH:46][C:45]=1[OH:52])[C:31](=[O:43])[N:32]2[CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39]>>[Br:27][C:28]1[CH:36]=[CH:35][CH:34]=[C:33]2[C:29]=1[C:30]([C:44]1[CH:49]=[C:48]([F:50])[C:47]([F:51])=[CH:46][C:45]=1[OH:52])([CH2:5][OH:16])[C:31](=[O:43])[N:32]2[CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39]
Reactant: CCCCCN1C(=O)C(c2cc3c(cc2O)OCO3)c2c(Br)cccc21
Reactant: CCOC(=O)CN1C(=O)C(c2cc(F)c(F)cc2O)c2c(Br)cccc21
Product: CCOC(=O)CN1C(=O)C(CO)(c2cc(F)c(F)cc2O)c2c(Br)cccc21

Procedure:
Following the procedure as described in PREPARATION 1E, and making non-critical variations to replace 4-bromo-3-(6-hydroxy-1,3-benzodioxol-5-yl)-1-pentyl-1,3-dihydro-2H-indol-2-one with ethyl [4-bromo-3-(4,5-difluoro-2-hydroxyphenyl)-2-oxo-2,3-dihydro-1H-indol-1-yl]acetate, the title compound was obtained (83%): MS (ES+) m/z 456.3 (M+1), 458.3 (M+1).
Reaction SMILES: [CH3:1][O:2][C:3]([C@@:5]12[CH2:14][N:13]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:12][CH2:11][C:10]1=[CH:9][C:8](=O)/[C:7](=[CH:23]\O)/[CH2:6]2)=[O:4].Cl.[F:26][C:27]1[CH:32]=[CH:31][C:30]([NH:33][NH2:34])=[CH:29][CH:28]=1.C([O-])(=O)C.[Na+]>C(O)(=O)C>[CH3:1][O:2][C:3]([C@@:5]12[CH2:14][N:13]([C:15]([O:17][C:18]([CH3:19])([CH3:21])[CH3:20])=[O:16])[CH2:12][CH2:11][C:10]1=[CH:9][C:8]1[N:33]([C:30]3[CH:31]=[CH:32][C:27]([F:26])=[CH:28][CH:29]=3)[N:34]=[CH:23][C:7]=1[CH2:6]2)=[O:4]
Reactant: COC(=O)[C@]12C/C(=C/O)C(=O)C=C1CCN(C(=O)OC(C)(C)C)C2
Reactant: NNc1ccc(F)cc1
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CC(=O)O
Product: COC(=O)[C@]12Cc3cnn(-c4ccc(F)cc4)c3C=C1CCN(C(=O)OC(C)(C)C)C2
Temperature: 25 °C
Reaction time: 1 h
Yield: 76.8 %

Procedure:
A mixture of (R)-7-[1-hydroxymeth-(Z)-ylidene]-6-oxo-4,6,7,8-tetrahydro-3H-isoquinoline-2,8a-dicarboxylic acid 2-tert-butyl ester 8a-methyl ester (3.8 g), 4-fluorophenylhydrazine hydrochloride (2.7 g), sodium acetate (1.4 g) and acetic acid (30 mL) was stirred at room temperature for 1 hour. The mixture was concentrated under reduced pressure, and the residue was partitioned between diethyl ether and 2.0 M aqueous hydrochloric acid solution. The organic phase was washed with water, aqueous potassium carbonate solution and brine, and then dried over sodium sulfate. The solvent was removed under reduced pressure, and the residue was triturated with a mixture of cyclohexane and diethyl ether to afford the title compound as a yellow solid (3.7 g). 1H NMR (CDCl3): δ 7.48-7.39 (m, 3H), 7.21-7.12 (m, 2H), 6.45-6.41 (s, 1H), 4.69-4.55 (d, 1H, J=13 Hz), 4.32-3.98 (m, 1H), 3.64 (s, 3H), 3.51-3.33 (m, 1H), 3.00-2.71 (m, 3H), 2.59-2.51 (d, 1H, J=16 Hz), 2.48-2.34 (m, 1H), 1.46 (s, 9H).
Reaction SMILES: I[C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.[C:10]([S-:12])#[N:11].[K+].CN(C=O)C>C1(C)C=CC=CC=1.O>[S:12]([C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1)[C:10]#[N:11]
Reactant: N#C[S-]
Reactant: O=Cc1ccc(I)cc1
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: O
Solvent: CN(C)C=O
Product: N#CSc1ccc(C=O)cc1
Temperature: 140 °C
Yield: 20.2 %

Procedure:
Under an argon atmosphere, a mixture of 4-iodobenzaldehyde (232 mg, 1.00 mmol), KSCN (95.0 mg, 1.00 mmol), CuSCN (120 mg, 1.00 mmol) and DMF (7.5 mL) was heated with stirring in an oil bath maintained at 140° C. for 12 h. After cooling, the mixture was diluted with toluene and water, and then filtered through a Celite bed. The aqueous phase was extracted with toluene, the organic fractions were combined and washed with water, dried and concentrated. The resulting dark oil was chromatographed on silica gel using centrifugal preparative chromatography to obtain off-white crystals (33 mg, 20%). mp 82-83° C.; 1H NMR (CDCl3) δ7.63, 7.92 (AA′BB′, 2H, ArH), 10.01 (s, 1H, CHO); 13C NMR (CDCl3) δ109.4, 129.3, 131.6, 132.9, 191.3; EI-MS obsd 163.0092, calcd exact mass 163.0092 (C8H5NOS); Anal. Calcd. for C8H5NOS: C, 58.88; H, 3.09; N, 8.58; S, 19.65; Found: C, 58.85; H, 2.99; N, 8.61; S, 19.68.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([NH:25][C:26]2[N:31]=[C:30]([C:32]3[C:40]4[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=4)[N:34]([CH3:41])[CH:33]=3)[CH:29]=[CH:28][N:27]=2)=[CH:5][C:6]([N+:22]([O-])=O)=[C:7]([N:9]([CH3:21])[CH2:10][CH2:11][N:12]([CH3:20])[C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH:8]=1.[NH4+].[Cl-].O>C(O)C.[Fe]>[NH2:22][C:6]1[CH:5]=[C:4]([NH:25][C:26]2[N:31]=[C:30]([C:32]3[C:40]4[C:35](=[CH:36][CH:37]=[CH:38][CH:39]=4)[N:34]([CH3:41])[CH:33]=3)[CH:29]=[CH:28][N:27]=2)[C:3]([O:2][CH3:1])=[CH:8][C:7]=1[N:9]([CH3:21])[CH2:10][CH2:11][N:12]([CH3:20])[C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:16])[CH3:17]
Reactant: COc1cc(N(C)CCN(C)C(=O)OC(C)(C)C)c([N+](=O)[O-])cc1Nc1nccc(-c2cn(C)c3ccccc23)n1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Solvent: O
Product: COc1cc(N(C)CCN(C)C(=O)OC(C)(C)C)c(N)cc1Nc1nccc(-c2cn(C)c3ccccc23)n1
Temperature: 100 °C
Yield: 94 %

Procedure:
tert-Butyl N-[2-[[5-methoxy-4-[[4-(1-methylindol-3-yl)pyrimidin-2-yl]amino]-2-nitrophenyl]-methylamino]ethyl]-N-methylcarbamate (Intermediate 172, 428 mg, 0.76 mmol), iron (255 mg, 4.57 mmol) and NH4Cl (30.6 mg, 0.57 mmol) were heated in ethanol (16 mL) and water (5.33 mL) at reflux for 1.5 h (heating block at 100° C.) and then the mixture was cooled and concentrated in vacuo. The resulting residue was triturated in 10% CH3OH/CH2Cl2 (30 mL) and filtered. The residues were triturated again with 10% CH3OH/CH2Cl2 (30 mL) and filtered. The combined filtrates were washed with brine, dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 0-5% CH3OH in CH2Cl2 gave the title compound (380 mg, 94%) as a light brown foam; 1H NMR: 1.41 (9H, s), 2.64 (3H, s), 2.80 (3H, s), 2.95 (2H, t), 3.34 (2H, t), 3.77 (3H, s), 3.89 (3H, s), 4.40 (2H, s), 6.78 (1H, s), 7.14-7.20 (2H, m), 7.23-7.27 (1H, m), 7.52 (1H, d), 7.55 (1H, s), 7.75 (1H, s), 8.28 (1H, d), 8.29 (1H, s), 8.42 (1H, d); m/z: ES+ MH+ 532.37.
Reaction SMILES: [N:1]1[CH:2]=[CH:3][N:4]2[C:8]3[CH:9]=[C:10]([NH2:13])[CH:11]=[CH:12][C:7]=3[S:6][C:5]=12.C(O[CH:17]=[C:18]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[C:19]([O:21][CH2:22][CH3:23])=[O:20])C>O(CC)CC>[N:1]1[CH2:2][CH2:3][N:4]2[C:8]3[CH:9]=[C:10]([NH:13][CH:17]=[C:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH:11]=[CH:12][C:7]=3[S:6][C:5]=12
Reactant: Nc1ccc2sc3nccn3c2c1
Reactant: CCOC=C(C(=O)OCC)C(=O)OCC
Solvent: CCOCC
Product: CCOC(=O)C(=CNc1ccc2c(c1)N1CCN=C1S2)C(=O)OCC
Temperature: 110 °C
Reaction time: 0.5 h
Yield: 95 %

Procedure:
A mixture of 5.5 parts of imidazo[2,1-b]benzothiazol-6-amine and 7.5 parts of diethyl 2-(ethoxymethylene)propanedioate is stirred for 30 minutes at 110° C. The solid product is suspended in 1,1'-oxybisethane. It is filtered off and dried, yielding 10 parts (95%) of diethyl 2-[(2,3-dihydroimidazo[2,1-b]benzothiazol-6-yl)aminomethylene]propanedioate; mp. 140° C.
Reaction SMILES: [CH:1]([NH:3][C:4]1[N:9]=[C:8]([C:10](=[N:36][O:37][CH3:38])[C:11]([NH:13][CH:14]2[C:34](=[O:35])[N:16]3[C:17]([C:21]([O:23]CC4C=CC([N+]([O-])=O)=CC=4)=[O:22])=[CH:18][CH2:19][S:20][C@H:15]23)=[O:12])[CH:7]=[CH:6][CH:5]=1)=[O:2].O>[Pd].O1CCCC1.CO.C(O)(=O)C>[CH:1]([NH:3][C:4]1[N:9]=[C:8]([C:10](=[N:36][O:37][CH3:38])[C:11]([NH:13][CH:14]2[C:34](=[O:35])[N:16]3[C:17]([C:21]([OH:23])=[O:22])=[CH:18][CH2:19][S:20][C@H:15]23)=[O:12])[CH:7]=[CH:6][CH:5]=1)=[O:2]
Reactant: CON=C(C(=O)NC1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=CCS[C@H]12)c1cccc(NC=O)n1
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: O
Product: CON=C(C(=O)NC1C(=O)N2C(C(=O)O)=CCS[C@H]12)c1cccc(NC=O)n1
Reaction time: 5 h
Yield: 74.1 %

Procedure:
10% Palladium on carbon (216 mg.) was added to a solution of 4-nitrobenzyl 7-[2-(6-formamidopyridin-2-yl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylate (540 mg.) in tetrahydrofuran (10 ml.), methanol (5 ml.), acetic acid (0.075 ml.), and water (0.75 ml.). The mixture was subjected to catalytic reduction at ambient temperature under ordinary pressure for 5 hours, and then allowed to stand overnight. After filtered off the catalyst, the filtrate was concentrated under reduced pressure. Ethyl acetate and an aqueous solution of sodium bicarbonate were added to the residue, and the aqueous layer was separated. The solution was adjusted to pH 2 with 10% hydrochloric acid. The appeared precipitates were collected by filtration, washed with water and dried to give 7-[2-(6-formamidopyridin-2-yl)-2-methoxyiminoacetamido]-3-cephem-4-carboxylic acid (300 mg.), mp. 202° to 204° C. (dec.).
Reaction SMILES: CC(C)([O-])C.[K+].[CH3:7][C:8]1[CH:13]=[CH:12][C:11]([SH:14])=[CH:10][CH:9]=1.[Br:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1Br.O>CN1CCCC1=O.C1(C)C=CC=CC=1>[C:8]1([CH3:7])[CH:13]=[CH:12][C:11]([S:14][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[Br:15])=[CH:10][CH:9]=1
Reactant: Cc1ccc(S)cc1
Reactant: Brc1ccccc1Br
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN1CCCC1=O
Solvent: O
Solvent: Cc1ccccc1
Product: Cc1ccc(Sc2ccccc2Br)cc1
Temperature: 100 °C

Procedure:
To a stirred solution of potassium tert-butoxide (75 g, 0.668 mol, 1.1 eq) in N-methyl-2-pyrrolidone (225 mL) a solution of 4-methylthiophenol (78 g, 0.628 mol, 1.0 eq) dissolved in N-methyl-2-pyrrolidone (225 mL) was added. To the reaction mixture was then added to 1,2-dibromobenzene (73 mL, 605 mol, 1.0 eq); once the addition was complete the reaction mixture was warmed to 100° C. and maintained at this temperature for approximately 22 hrs. (The reaction is monitored by HPLC). After cooling to room temperature water (750 mL) and toluene (375 mL) were added, the phases separated, and the water phase extracted with toluene (250 mL). The organic phases were combined and the organic phase was concentrated by vacuum distillation. Once the distillation was complete, the residue was cooled and methanol (750 mL) added. The solvents were removed from the organic phase by vacuum distillation and further methanol (250 mL) added. Stirring over night at room temperature precipitated 2-(4-tolylsulfanyl)-phenyl bromide which was isolated by filtration, washed with methanol (260 mL) and dried in vacuum. Yield=120.8 g.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[C:6]([S:10]([O:13]C2C(F)=C(F)C(F)=C(F)C=2F)(=[O:12])=O)=[C:5]([CH3:25])[CH:4]=1.[OH:26][CH2:27][CH:28]1[CH2:33][CH2:32][CH2:31][CH2:30][NH:29]1>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.CN(C)C=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH3:25])[C:6]([S:10]([N:29]2[CH2:30][CH2:31][CH2:32][CH2:33][CH:28]2[CH2:27][OH:26])(=[O:12])=[O:13])=[C:7]([CH3:9])[CH:8]=1
Reactant: OCC1CCCCN1
Reactant: COc1cc(C)c(S(=O)(=O)Oc2c(F)c(F)c(F)c(F)c2F)c(C)c1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Cl-]
Solvent: CN(C)C=O
Product: COc1cc(C)c(S(=O)(=O)N2CCCCC2CO)c(C)c1
Temperature: 110 °C
Reaction time: 1 h

Procedure:
Perfluorophenyl 4-methoxy-2,6-dimethylbenzenesulfonate (1 g, 2.616 mmol), 2-(hydroxymethyl)-piperidine (1.61 g, 13.079 mmol) and tetrabutylammonium chloride (1.45 g, 5.231 mmol) were dissolved in N,N-dimethylformamide (10 ml) and the solution was stirred at 110° C. for 1 h. The solvent was removed in vacuo, the residue was dissolved in ethyl acetate and the solution was washed with ammonium chloride solution (10%, 20 ml), dried over sodium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (silica gel) with diethyl ether/hexane/methylene chloride (1:1:1). Yield: 0.63 g (76%)
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]#[N:13])=[CH:9][CH:10]=2)[C:5](Cl)=[N:4][N:3]=1.[Cl:15][C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][C:23]=1[CH3:24])[CH2:19][NH2:20].C1CCN2C(=NCCC2)CC1>CN1CCCC1=O>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]#[N:13])=[CH:9][CH:10]=2)[C:5]([NH:20][CH2:19][C:18]2[CH:21]=[CH:22][C:23]([CH3:24])=[C:16]([Cl:15])[CH:17]=2)=[N:4][N:3]=1
Reactant: Cc1ccc(CN)cc1Cl
Reactant: N#Cc1ccc2c(Cl)nnc(Cl)c2c1
Solvent: C1CCC2=NCCCN2CC1
Solvent: CN1CCCC1=O
Product: Cc1ccc(CNc2nnc(Cl)c3ccc(C#N)cc23)cc1Cl

Procedure:
1,4-Dichlorophthalazine-6-carbonitrile and 3-chloro-4-methylbenzylamine were stirred at room temperature in 1-methyl-2-pyrrolidinone in the presence of DBU, whereby the title compound was obtained as a less polar compound.
Reaction SMILES: [CH3:1][NH:2][CH:3]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:7]([C:14](=[O:31])[C:15]2[CH:20]=[CH:19][C:18]([NH:21][C:22](=[O:30])[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[CH3:29])=[CH:17][CH:16]=2)[CH2:6][CH2:5][CH2:4]1.C(N(CC)CC)C.[CH3:39][S:40](Cl)(=[O:42])=[O:41].O>ClCCl>[CH3:1][N:2]([CH:3]1[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=2[N:7]([C:14](=[O:31])[C:15]2[CH:20]=[CH:19][C:18]([NH:21][C:22](=[O:30])[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[CH3:29])=[CH:17][CH:16]=2)[CH2:6][CH2:5][CH2:4]1)[S:40]([CH3:39])(=[O:42])=[O:41]
Reactant: CS(=O)(=O)Cl
Reactant: CNC1CCCN(C(=O)c2ccc(NC(=O)c3ccccc3C)cc2)c2ccccc21
Solvent: CCN(CC)CC
Solvent: O
Solvent: ClCCl
Product: Cc1ccccc1C(=O)Nc1ccc(C(=O)N2CCCC(N(C)S(C)(=O)=O)c3ccccc32)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 5-methylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.6 g) in dichloromethane (10 ml) is added triethylamine (0.24 ml). Subsequently, thereto is added methanesulfonyl chloride (0.14 ml) under ice-cooling, and then, the mixture is warmed to room temperature and stirred overnight. Water is added to the reaction solution, extracted three times with dichloromethane. The extract is washed with saturated saline solution, and dried over magnesium sulfate. The solvent is distilled off and the resulting residue is purified by silica gel column chromatography (eluent; dichloromethane:methanol=20:1), and recrystallized from ethanol to give 5-(N-methyl-N-methanesulfonylamino)-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine (0.48 g) as colorless scales, m.p. 197°-198° C.
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([N:8]2[CH2:12][CH2:11][CH2:10][C@H:9]2[C:13]([CH3:21])([CH3:20])[O:14][SiH2:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH:7]=1.[CH3:22][N:23]1[C:32]2[C:27](=[CH:28][C:29](B3OC(C)(C)C(C)(C)O3)=[CH:30][CH:31]=2)[CH2:26][CH2:25][C:24]1=[O:42].C([O-])([O-])=O.[Na+].[Na+].C([O-])(O)=O.[Na+]>CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.CN(C=O)C>[C:16]([SiH2:15][O:14][C:13]([CH3:21])([CH3:20])[C@@H:9]1[CH2:10][CH2:11][CH2:12][N:8]1[C:6]1[CH:7]=[C:2]([C:29]2[CH:28]=[C:27]3[C:32](=[CH:31][CH:30]=2)[N:23]([CH3:22])[C:24](=[O:42])[CH2:25][CH2:26]3)[CH:3]=[N:4][CH:5]=1)([CH3:19])([CH3:18])[CH3:17]
Reactant: CC(C)(C)[SiH2]OC(C)(C)[C@@H]1CCCN1c1cncc(Br)c1
Reactant: CN1C(=O)CCc2cc(B3OC(C)(C)C(C)(C)O3)ccc21
Agent: Cl[Pd]Cl
Agent: O=C([O-])O
Agent: O=C([O-])[O-]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CN1C(=O)CCc2cc(-c3cncc(N4CCC[C@H]4C(C)(C)O[SiH2]C(C)(C)C)c3)ccc21
Temperature: 120 °C
Yield: 90.4 %

Procedure:
A microwave vial was charged with 3-bromo-5-[(S)-2-(tert-butyl-dimethyl-silanyloxymethyl)-pyrrolidin-1-yl]-pyridine (0.091 g, 0.245 mmol), 1-methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-quinolin-2-one (intermediate A-1, 0.077 g, 0.270 mmol) and DMF (1.5 mL). The reaction mixture was purged with Argon; then, bis(triphenylphosphine)palladium(II)chloride (0.017 g, 0.025 mmol), followed by a 1N Na2CO3 aqueous solution (0.980 mL, 0.980 mmol) were added and the reaction mixture was heated in the microwave at 120° C. for 30 min. The reaction mixture was diluted with EtOAc, poured into aq. NaHCO3 (10 mL) and the aqueous layer was extracted with EtOAc (2×40 mL). Combined organics were washed with brine, dried over Na2SO4, filtered and evaporated. The residue was purified by silica gel flash chromatography eluting with a 0 to 5% MeOH-DCM gradient to give the title compound (0.1 g, 90%) as a white solid. MS: 452.1 (M+H+).
Reaction SMILES: [Br:1][C:2]1[N:7]=[C:6]([CH:8]=O)[CH:5]=[CH:4][CH:3]=1.Cl.[CH:11]1([NH:16][C:17](=[O:20])[CH2:18][NH2:19])[CH2:15][CH2:14][CH2:13][CH2:12]1>>[Br:1][C:2]1[N:7]=[C:6]([CH2:8][NH:19][CH2:18][C:17]([NH:16][CH:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)=[O:20])[CH:5]=[CH:4][CH:3]=1
Reactant: O=Cc1cccc(Br)n1
Reactant: NCC(=O)NC1CCCC1
Agent: Cl
Product: O=C(CNCc1cccc(Br)n1)NC1CCCC1

Procedure:
The title compound was prepared by using the procedure listed in Example 47, Step 7 with 6-bromopyridine-2-carbaldehyde (1.0 g, 5.38 mmol) and N-cyclopentylglycinamide hydrochloride (0.96 g, 5.38 mmol) as the starting materials.
Reaction SMILES: [CH:1](=O)[CH2:2][CH:3]([CH3:5])[CH3:4].[CH3:7][C:8]([CH3:10])=[O:9]>>[CH3:4][CH:3]([CH3:5])[CH2:2][CH2:1][CH2:7][C:8](=[O:9])[CH3:10]
Reactant: CC(C)=O
Reactant: CC(C)CC=O
Product: CC(=O)CCCC(C)C

Procedure:
To aid comprehension, the reaction will be explained here by the example of the reaction of acetone with isovaleraldehyde to produce 6-methylheptan-2-one. The reaction takes place “in situ” via the stage of aldol condensation with the formation of the corresponding β-hydroxyketone, which is not isolated. Dehydration to 6-methylhept-3-en-2-one takes place under the reaction conditions, and this is hydrogenated selectively to the corresponding methylketone with the hydrogenation catalyst distributed homogeneously in the aqueous catalyst phase.