Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CO[C:3](=[O:31])[C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH:14]=[C:13]([C:15]3[C:16]([C:24]4[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=4)=[N:17][O:18][C:19]=3[C:20]([F:23])([F:22])[F:21])[N:12]=[CH:11]2)=[N:6][CH:5]=1.COC(=O)C1C=CC(N2C=C(C3[C:47]([C:55]4[CH:60]=[CH:59]C=CC=4)=[N:48]OC=3C(F)(F)F)N=C2)=CC=1>>[Cl:30][C:27]1[CH:28]=[CH:29][C:24]([C:16]2[C:15]([C:13]3[N:12]=[CH:11][N:10]([C:7]4[CH:8]=[CH:9][C:4]([C:3]([NH:48][CH2:47][CH:55]5[CH2:60][CH2:59]5)=[O:31])=[CH:5][N:6]=4)[CH:14]=3)=[C:19]([C:20]([F:21])([F:23])[F:22])[O:18][N:17]=2)=[CH:25][CH:26]=1
Reactant: COC(=O)c1ccc(-n2cnc(-c3c(-c4ccccc4)noc3C(F)(F)F)c2)cc1
Reactant: COC(=O)c1ccc(-n2cnc(-c3c(-c4ccc(Cl)cc4)noc3C(F)(F)F)c2)nc1
Product: O=C(NCC1CC1)c1ccc(-n2cnc(-c3c(-c4ccc(Cl)cc4)noc3C(F)(F)F)c2)nc1
Yield: 83 %

Procedure:
As described for Example 10, 6-{4-[3-(4-chloro-phenyl)-5-trifluoromethyl-isoxazol-4-yl]-imidazol-1-yl}-nicotinic acid methyl ester (100 mg, 0.23 mmol), instead of 4-[4-(3-phenyl-5-trifluoromethyl-isoxazol-4-yl)-imidazol-1-yl]-benzoic acid methyl ester was converted, to the title compound (90 mg, 83%) which was obtained as a white solid. MS: m/e=488.1 [M+H]+.
Reaction SMILES: Cl.[CH2:2]([O:9][C:10]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:11]=1[CH2:12][CH2:13][CH2:14][CH:15]2[C:20]([N:22]([C:29]1[CH:30]=[N:31][C:32]([CH:35]([CH3:37])[CH3:36])=[CH:33][CH:34]=1)[CH2:23][C:24]1[CH:25]=[N:26][NH:27][CH:28]=1)=[O:21])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:38][C:39]1[CH:46]=[CH:45][C:42]([CH2:43]Cl)=[CH:41][CH:40]=1>>[CH2:2]([O:9][C:10]1[CH:19]=[CH:18][CH:17]=[C:16]2[C:11]=1[CH2:12][CH2:13][CH2:14][CH:15]2[C:20]([N:22]([C:29]1[CH:30]=[N:31][C:32]([CH:35]([CH3:37])[CH3:36])=[CH:33][CH:34]=1)[CH2:23][C:24]1[CH:25]=[N:26][N:27]([CH2:38][C:39]2[CH:46]=[CH:45][C:42]([CH3:43])=[CH:41][CH:40]=2)[CH:28]=1)=[O:21])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: CC(C)c1ccc(N(Cc2cn[nH]c2)C(=O)C2CCCc3c(OCc4ccccc4)cccc32)cn1
Reactant: Cc1ccc(CCl)cc1
Agent: Cl
Product: Cc1ccc(Cn2cc(CN(C(=O)C3CCCc4c(OCc5ccccc5)cccc43)c3ccc(C(C)C)nc3)cn2)cc1
Yield: 74.8 %

Procedure:
By the reaction and treatment in the same manner as in Example 271 using 5-benzyloxy-N-(6-isopropylpyridin-3-yl)-N-[(pyrazol-4-yl)methyl]-1,2,3,4-tetrahydronaphthalene-1-carboxamide hydrochloride (0.78 g) and 4-methylbenzyl chloride (0.42 g) as starting materials, 5-benzyloxy-N-(6-isopropylpyridin-3-yl)-N-({1-[(4-methylphenyl)methyl]pyrazol-4-yl}methyl)-1,2,3,4-tetrahydronaphthalene-1-carboxamide (0.66 g) was obtained.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[C:8]([CH2:9][CH3:10])=[N:7][C:6]2[N:11]([CH2:14][CH3:15])[N:12]=[CH:13][C:5]=2[C:4]=1[NH:16][CH:17]1[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.[CH3:23][C:24]([O:27][C:28]([NH:30][C:31]1[CH:39]=[CH:38][CH:37]=[CH:36][C:32]=1[C:33](O)=[O:34])=[O:29])([CH3:26])[CH3:25].C(N(CC)C(C)C)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>CN(C)C=O>[CH2:14]([N:11]1[C:6]2=[N:7][C:8]([CH2:9][CH3:10])=[C:3]([CH2:2][NH:1][C:33]([C:32]3[CH:36]=[CH:37][CH:38]=[CH:39][C:31]=3[NH:30][C:28](=[O:29])[O:27][C:24]([CH3:25])([CH3:23])[CH3:26])=[O:34])[C:4]([NH:16][CH:17]3[CH2:18][CH2:19][O:20][CH2:21][CH2:22]3)=[C:5]2[CH:13]=[N:12]1)[CH3:15]
Reactant: CC(C)(C)OC(=O)Nc1ccccc1C(=O)O
Reactant: CCc1nc2c(cnn2CC)c(NC2CCOCC2)c1CN
Agent: F[P-](F)(F)(F)(F)F
Agent: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCc1nc2c(cnn2CC)c(NC2CCOCC2)c1CNC(=O)c1ccccc1NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 4 h
Yield: 67.3 %

Procedure:
A mixture of Intermediate 7 (250 mg, 0,83 mmol) and 2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)benzoic acid (196 mg, 0.83 mmol, e.g. available from Fluka) in N,N-dimethylformamide (4 ml) was treated with N,N-diisopropylethylamine (0.569 ml, 3.3 mmol) and (1H-1,2,3-benzotriazol-1-yloxy)(tri-1-pyrrolidinyl)phosphonium hexafluorophosphate (472 mg, 0.91 mmol) and allowed to stir at room temperature for 4 hours. An additional portion of (1H-1,2,3-benzotriazol-1-yloxy)(tri-1-pyrrolidinyl)phosphonium hexafluorophosphate (0.5 equiv., 0.41 mmol) was added and the mixture stirred for an additional hour. The solvent was evaporated and the residue dissolved in ethyl acetate (50 ml) and washed with aqueous sodium bicarbonate solution (2×50 ml); the organic fraction was dried (Na2SO4) and evaporated. The residue was purified by chromatography on silica gel (50 g SPE cartridge), eluting with a gradient of 0-100% ethyl acetate/cyclohexane followed by a gradient of 0-20% methanol/ethyl acetate over 40 minutes. Fractions containing product were pooled and evaporated to give the title compound (292 mg). LCMS showed MH+=523; TRET=2.71 min.
Reaction SMILES: [C:1]1([CH:8]=[CH:7][C:5]([OH:6])=[CH:4][CH:3]=1)[OH:2].[C:9]([O:12][C:13]1[CH:21]=[CH:20][C:16]([C:17](O)=[O:18])=[CH:15][CH:14]=1)(=[O:11])[CH3:10]>>[C:9]([O:12][C:13]1[CH:21]=[CH:20][C:16]([C:17]([O:2][C:1]2[CH:8]=[CH:7][C:5]([O:6][C:17](=[O:18])[C:16]3[CH:20]=[CH:21][C:13]([O:12][C:9](=[O:11])[CH3:10])=[CH:14][CH:15]=3)=[CH:4][CH:3]=2)=[O:18])=[CH:15][CH:14]=1)(=[O:11])[CH3:10]
Reactant: CC(=O)Oc1ccc(C(=O)O)cc1
Reactant: Oc1ccc(O)cc1
Product: CC(=O)Oc1ccc(C(=O)Oc2ccc(OC(=O)c3ccc(OC(C)=O)cc3)cc2)cc1

Procedure:
Using the procedure described above, this compound was prepared from hydroquinone and 4-acetoxybenzoic acid. The crude product was recrystallized from methyl isobutyl ketone (18 ml/g) giving white platelets with a m.p. of 185.0° C. to 186.5° C.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:29])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([S:12](=[O:28])(=[O:27])[NH:13][C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:25][CH2:24][C:23](=O)[CH2:22][CH2:21]3)=[CH:16][CH:15]=2)=[CH:8][CH:7]=1.[OH:30][C@@H:31]([CH2:44][NH2:45])[CH2:32][O:33][C:34]1[C:42]2[NH:41][C:40](=[O:43])[NH:39][C:38]=2[CH:37]=[CH:36][CH:35]=1>>[CH3:1][O:2][C:3](=[O:29])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([S:12]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([N:20]3[CH2:25][CH2:24][CH:23]([NH:45][CH2:44][C@H:31]([OH:30])[CH2:32][O:33][C:34]4[C:42]5[NH:41][C:40](=[O:43])[NH:39][C:38]=5[CH:37]=[CH:36][CH:35]=4)[CH2:22][CH2:21]3)=[CH:18][CH:19]=2)(=[O:28])=[O:27])=[CH:8][CH:7]=1
Reactant: NC[C@H](O)COc1cccc2[nH]c(=O)[nH]c12
Reactant: COC(=O)COc1ccc(S(=O)(=O)Nc2ccc(N3CCC(=O)CC3)cc2)cc1
Product: COC(=O)COc1ccc(S(=O)(=O)Nc2ccc(N3CCC(NC[C@H](O)COc4cccc5[nH]c(=O)[nH]c45)CC3)cc2)cc1

Procedure:
The title compound was prepared from {4-[4-(4-oxo-piperidin-1-yl)-phenylsulfamoyl]-phenoxy}-acetic acid methyl ester (which was obtained in Example 232) and (S)-4-[2-hydroxy-3-aminopropoxy]-1,3-dihydro-2H-benzimidazol-2-one (U.S. Pat. No. 5,786,356/1998) according to the procedure of Example 278 as a pale yellowish solid; 1H NMR (300 MHz, DMSO-d6) δ 1.20–1.40 (m, 2 H), 1.75–1.90 (m, 2 H), 2.50–2.85 (m, 5 H), 3.30–3.50 (m, 2 H), 3.69 (s, 3 H), 3.80–4.05 (m, 3 H), 4.87 (s, 2 H), 6.56 (d, J=7.8 Hz, 1 H), 6.61 (d, J=8.1 Hz, 1 H), 6.65–6.90 (m, 5 H), 7.02 (d, J=9.0 Hz, 2 H), 7.59 (d, J=9.0 Hz, 2H), 10.60 (s, 1 H), 10.75 (brs, 1 H); MS (ES) m/z: 626.1 (MH+); HRMS Calcd. for C30H36N5O8S (MH+): 626.2285. Found: 626.2298.
Reaction SMILES: C([O:8][C:9]1[CH:10]=[C:11]([C:15]2[N:19]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=3)[N:18]=[C:17]([C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH:16]=2)[CH:12]=[CH:13][CH:14]=1)C1C=CC=CC=1>C(O)(=O)C.[Pd]>[Cl:26][C:22]1[CH:21]=[C:20]([N:19]2[C:15]([C:11]3[CH:12]=[CH:13][CH:14]=[C:9]([OH:8])[CH:10]=3)=[CH:16][C:17]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[N:18]2)[CH:25]=[CH:24][CH:23]=1
Reactant: CCOC(=O)c1cc(-c2cccc(OCc3ccccc3)c2)n(-c2cccc(Cl)c2)n1
Agent: [Pd]
Solvent: CC(=O)O
Product: CCOC(=O)c1cc(-c2cccc(O)c2)n(-c2cccc(Cl)c2)n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 84 %

Procedure:
19.1 g (44.1 mmol) of the compound of Example 43A are provided in 367 ml of conc. acetic acid, 23.5 g (11.0 mmol) of palladium on activated carbon (5%) are added, and the mixture is stirred under a hydrogen atmosphere at room temperature overnight. The reaction mixture is subsequently filtered, the filtrate is concentrated, the residue is taken up in dichloromethane and washed with an aqueous sodium bicarbonate solution, and the organic phase is dried over sodium sulfate and concentrated. 12.7 g of the title compound with 63% purity (53% of theory) are obtained.
Reaction SMILES: [OH:1][CH:2]1[CH2:7][NH:6][CH2:5][C:4]2[S:8][CH:9]=[CH:10][C:3]1=2.[C:11]1([N:17]=[C:18]=[O:19])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>C1C=CC=CC=1>[OH:1][CH:2]1[CH2:7][N:6]([C:18](=[O:19])[NH:17][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:5][C:4]2[S:8][CH:9]=[CH:10][C:3]1=2
Reactant: O=C=Nc1ccccc1
Reactant: OC1CNCc2sccc21
Solvent: c1ccccc1
Product: O=C(Nc1ccccc1)N1Cc2sccc2C(O)C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 65 %

Procedure:
To a solution of 4-hydroxy-4,5,6,7-tetrahydro-thieno[2,3-c]-pyridine (5.6 g; 36.2 mmoles) in benzene (40 cc), is added dropwise a mixture of phenyl isocyanate (4.3 g; 36.2 mmoles) in benzene (10 ml). After stirring during 2 hours at room temperature, the resulting precipitate is filtered off, washed with ether and dried in vacuo. On recrystallization from ethanol, the desired product is obtained in a yield of 65% (M.p. = 200° C).
Reaction SMILES: C([N:8]([CH2:54][C@@H:55]([C:64]1[CH:73]=[CH:72][C:71]([O:74]CC2C=CC=CC=2)=[C:70]2[C:65]=1[CH:66]=[CH:67][C:68](=[O:82])[NH:69]2)[O:56][Si:57]([C:60]([CH3:63])([CH3:62])[CH3:61])([CH3:59])[CH3:58])[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]2[CH:21]=[C:22]([CH2:26][NH:27][C:28]([CH2:30][CH2:31][N:32]3[CH2:37][CH2:36][CH:35]([O:38][C:39](=[O:53])[NH:40][C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=4[C:47]4[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=4)[CH2:34][CH2:33]3)=[O:29])[CH:23]=[CH:24][CH:25]=2)=[O:19])=[CH:13][CH:12]=1)C1C=CC=CC=1>CCO.CC(O)=O.[Pd]>[Si:57]([O:56][C@H:55]([C:64]1[CH:73]=[CH:72][C:71]([OH:74])=[C:70]2[C:65]=1[CH:66]=[CH:67][C:68](=[O:82])[NH:69]2)[CH2:54][NH:8][CH2:9][CH2:10][C:11]1[CH:12]=[CH:13][C:14]([NH:17][C:18]([C:20]2[CH:21]=[C:22]([CH2:26][NH:27][C:28]([CH2:30][CH2:31][N:32]3[CH2:37][CH2:36][CH:35]([O:38][C:39](=[O:53])[NH:40][C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=4[C:47]4[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=4)[CH2:34][CH2:33]3)=[O:29])[CH:23]=[CH:24][CH:25]=2)=[O:19])=[CH:15][CH:16]=1)([C:60]([CH3:63])([CH3:61])[CH3:62])([CH3:59])[CH3:58]
Reactant: CC(C)(C)[Si](C)(C)O[C@@H](CN(CCc1ccc(NC(=O)c2cccc(CNC(=O)CCN3CCC(OC(=O)Nc4ccccc4-c4ccccc4)CC3)c2)cc1)Cc1ccccc1)c1ccc(OCc2ccccc2)c2[nH]c(=O)ccc12
Agent: [Pd]
Solvent: CC(=O)O
Solvent: CCO
Product: CC(C)(C)[Si](C)(C)O[C@@H](CNCCc1ccc(NC(=O)c2cccc(CNC(=O)CCN3CCC(OC(=O)Nc4ccccc4-c4ccccc4)CC3)c2)cc1)c1ccc(O)c2[nH]c(=O)ccc12
Reaction time: 8 h
Yield: 75.9 %

Procedure:
A solution of biphenyl-2-ylcarbamic acid 1-[2-({3-[4-(2-{benzyl-[(R)-2-(8-benzyloxy-2-oxo-1,2-dihydroquinolin-5-yl)-2-(tert- butyldimethylsilanyloxy)ethyl]-amino}ethyl)phenylcarbamoyl]phenyl}methylcarbamoyl)ethyl]piperidin-4-yl ester (1.74 g, 1.56 mmol) in EtOH (12.2 mL) and AcOH (0.122 mL) was flushed with nitrogen for 3 min. Palladium on carbon (10%, ˜50% water, 0.18 g) was added and the reaction mixture was flushed with hydrogen for 4 min. The mixture was stirred under a hydrogen atmosphere (balloon) overnight and then filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (0-15% MeOH in DCM) to give the title compound (1.11 g, 76% yield) as a thick brownish liquid.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][NH:5][C:4](=[O:8])[C:3]=1[N+:9]([O-:11])=[O:10].C([O-])(=O)C.[Na+].[Br:17]Br>C(O)(=O)C.C(OCC)(=O)C>[Br:17][C:7]1[C:2]([CH3:1])=[C:3]([N+:9]([O-:11])=[O:10])[C:4](=[O:8])[NH:5][CH:6]=1
Reactant: Cc1cc[nH]c(=O)c1[N+](=O)[O-]
Reactant: BrBr
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: Cc1c(Br)c[nH]c(=O)c1[N+](=O)[O-]
Reaction time: 5.5 h
Yield: 90 %

Procedure:
To a stirred solution of 4-methyl-3-nitro-2-pyridone (0.45 g, 2.9 mmol) in glacial acetic acid (3 mL) was added sodium acetate (0.24 g) followed by bromine (0.15 mL) dropwise. After 5.5 hours, the mixture was diluted with ethyl acetate, washed with water, dried, filtered and concentrated to give 5-bromo-4-methyl-3-nitro-2-pyridone (0.62 g, 2.6 mmol, 90%).
Reaction SMILES: [CH3:1][O:2][CH2:3][C@@H:4]([NH:6][C:7]([C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15](Br)[N:16]=2)[N:11]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[CH:10]=1)=[O:8])[CH3:5].[F:27][C:28]1[CH:29]=[C:30]([F:50])[C:31]2[N:32]([CH:34]=[N:35][C:36]=2[Sn](CCCC)(CCCC)CCCC)[CH:33]=1>CN(C=O)C.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.[Cu]I>[CH3:1][O:2][CH2:3][C@@H:4]([NH:6][C:7]([C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:36]3[N:35]=[CH:34][N:32]4[CH:33]=[C:28]([F:27])[CH:29]=[C:30]([F:50])[C:31]=34)[N:16]=2)[N:11]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[CH:10]=1)=[O:8])[CH3:5]
Reactant: COC[C@H](C)NC(=O)c1cn(COCC[Si](C)(C)C)c2ncc(Br)nc12
Reactant: CCCC[Sn](CCCC)(CCCC)c1ncn2cc(F)cc(F)c12
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Product: COC[C@H](C)NC(=O)c1cn(COCC[Si](C)(C)C)c2ncc(-c3ncn4cc(F)cc(F)c34)nc12
Temperature: 90 °C
Reaction time: 1.5 h
Yield: 94 %

Procedure:
In a round-bottomed flask, 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide (125 mg, 0.28 mmol) and 6,8-difluoro-1-tributylstannyl-imidazo[1,5-a]pyridine (458 mg, 0.62 mmol) were dissolved in DMF (2.5 ml). The flask was evacuated and backfilled with argon then tetrakis(triphenylphosphine)palladium (0) (17 mg, 0.015 mmol) and copper (I) iodide (11 mg, 0.058 mmol) were added. The reaction mixture was stirred at 90° C. in an oil bath for 1.5 h then cooled to room temperature, quenched with water and extracted with diethyl ether (2×). The combined organic layers were washed twice with water and once with brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed twice over silica gel with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-3% MeOH) to afford 136 mg (89%) of 2-(6,8-difluoro-imidazo[1,5-a]pyridin-1-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-methoxy-1-methyl-ethyl)-amide as a yellow solid.
Reaction SMILES: [C:1]([OH:5])(=O)[CH:2]=[CH2:3].[C:6]([OH:10])(=O)[CH:7]=[CH2:8].[C:11](O)(=[O:14])C=C.C(C(CO)(CO)CC)O.C(C1C=C(CC)C2SC3C(=CC=CC=3)C(=O)C=2C=1)C>[O-][Ti]([O-])=O.[Ba+2].C(O)C>[CH3:11][O:14][CH:7]([CH2:6][O:10][CH:2]([CH2:1][OH:5])[CH3:3])[CH3:8]
Reactant: C=CC(=O)O
Agent: O=[Ti]([O-])[O-]
Agent: CCC(CO)(CO)CO
Agent: CCc1cc(CC)c2sc3ccccc3c(=O)c2c1
Solvent: CCO
Product: COC(C)COC(C)CO
Yield: 39.4 %

Procedure:
A slurry obtained by mixing 6.2 g of a borosilicate glass powder, 56.0 g of barium titanate, 6.2 g of an acrylic organic binder containing hydroxyl groups, 3.1 g of ethanol, 3.0 g of trimethylolpropane triacrylate, 1.2 g of 2-methyl-1-[4-(methylthio)phenyl]-2-morphorinopropane-1-on, 0.3 g of 2,4-diethylthioxanthone and 0.5 g of dipropyleneglycol monomethyl ether was formed into a sheet by the doctor blade method. The sheet was dried at 100° C. to obtain a photosensitive dielectric ceramic green sheet with a thickness of 30 μm.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:21]=[CH:20][C:6]2[NH:7][C:8]([S:10][CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[C:13]=3[NH2:19])=[N:9][C:5]=2[CH:4]=1.C([O:24]CC)C>>[CH3:1][O:2][C:3]1[CH:21]=[CH:20][C:6]2[NH:7][C:8]([S:10]([CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([CH3:18])[C:13]=3[NH2:19])=[O:24])=[N:9][C:5]=2[CH:4]=1
Reactant: CCOCC
Reactant: COc1ccc2[nH]c(SCc3cccc(C)c3N)nc2c1
Product: COc1ccc2[nH]c(S(=O)Cc3cccc(C)c3N)nc2c1

Procedure:
The title compound was prepared by the method of Example 3 using 2.00 g of the title product of Example 35 instead of the title product of Example 2. Trituration with diethylether gave 1.58 g of the title compound: m.p. 142-144° C. Analysis. Calc'd. for C16H17N3O2S: C, 60.93; H, 5.43; N, 13.32; S, 10.17. Found: C, 60.60; H, 5.42; N, 12.83; S, 9.86.
Reaction SMILES: [CH2:1]([O:8][C:9](Cl)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:12]([O:14][C:15](=[O:21])[C:16]([CH3:20])([CH3:19])[CH2:17][NH2:18])[CH3:13]>C(OCC)(=O)C.C(=O)([O-])O.[Na+]>[CH2:12]([O:14][C:15](=[O:21])[C:16]([CH3:20])([CH3:19])[CH2:17][NH:18][C:9]([O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:10])[CH3:13]
Reactant: CCOC(=O)C(C)(C)CN
Reactant: O=C(Cl)OCc1ccccc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Product: CCOC(=O)C(C)(C)CNC(=O)OCc1ccccc1
Reaction time: 2 h

Procedure:
31 ml of 90% chloroformic acid benzyl ester are slowly added, at 0°-5° C., to 29.04 g of 3-amino-2,2-dimethylpropionic acid ethyl ester in 500 ml of ethyl acetate and 250 ml of 1M sodium hydrogen carbonate solution. The reaction mixture is stirred for 2 hours at 0°-5° C. and extracted with ethyl acetate. The organic phases are washed with saturated sodium chloride solution and then concentrated. The evaporation residue is purified by FC (1 kg of silica gel; eluant: ethyl acetate/hexane=1:3). The title compound is obtained: Rf (ethyl acetate/hexane=1:3)=0.28.
Reaction SMILES: B(Br)(Br)Br.[Br:5][C:6]1[CH:15]=[C:14]2[C:9]([CH:10]=[CH:11][N:12]=[CH:13]2)=[CH:8][C:7]=1[O:16]C.C([O-])(O)=O.[Na+]>ClCCl>[Br:5][C:6]1[CH:15]=[C:14]2[C:9]([CH:10]=[CH:11][N:12]=[CH:13]2)=[CH:8][C:7]=1[OH:16]
Reactant: COc1cc2ccncc2cc1Br
Agent: BrB(Br)Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: Oc1cc2ccncc2cc1Br
Temperature: 25 °C
Reaction time: 18 h
Yield: 63.8 %

Procedure:
3.6 mL (9.5 g, 37.8 mmol) of BBr3 were added at 0° C. to a solution of 4.5 g (18.9 mmol) 7-bromo-6-methoxy isoquinoline in 30 mL dichloromethane and stirred for 18 h at room temperature. Aqueous NaHCO3-solution was added to adjust the pH to 8. Extraction with chloroform/isopropanol (3/1) followed by drying over sodium sulfate and removal of the solvents gave 2.7 g (64%) of compound 1.
Reaction SMILES: CO[C:3](=[O:17])[C:4]1[C:9]([C:10]([F:13])([F:12])[F:11])=[CH:8][C:7]([Cl:14])=[CH:6][C:5]=1[CH2:15]Br.[F:18][C:19]([F:30])([F:29])[O:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25][NH2:26])=[CH:23][CH:22]=1.C([O-])([O-])=O.[K+].[K+].C(OCC)(=O)C>C1(C)C=CC=CC=1.CCCCCC>[Cl:14][C:7]1[CH:6]=[C:5]2[C:4](=[C:9]([C:10]([F:11])([F:12])[F:13])[CH:8]=1)[C:3](=[O:17])[N:26]([CH2:25][C:24]1[CH:27]=[CH:28][C:21]([O:20][C:19]([F:18])([F:29])[F:30])=[CH:22][CH:23]=1)[CH2:15]2
Reactant: COC(=O)c1c(CBr)cc(Cl)cc1C(F)(F)F
Reactant: NCc1ccc(OC(F)(F)F)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCCCCC
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Product: O=C1c2c(cc(Cl)cc2C(F)(F)F)CN1Cc1ccc(OC(F)(F)F)cc1
Temperature: 100 °C
Reaction time: 2 h
Yield: 47 %

Procedure:
A mixture of 4-chloro-2-bromomethyl-6-trifluoromethyl-benzoic acid methyl ester (1.33 g, 4.0 mmol), 4-trifluoromethoxy-benzylamine (0.610 mL, 4.1 mmol), and K2CO3 (0.691 g, 5.0 mmol) in toluene (10 mL) was heated with stirring at 100° C. for 2 h. Workup and silica gel column chromatography of the product using 30% ethyl acetate in hexane afforded 5-chloro-2-(4-trifluoromethoxy-benzyl)-7-trifluoromethyl-2,3-dihydro-isoindol-1-one (0.770 g, 47%). 1H NMR (300 MHz, CDCl3): δ (ppm) 4.34 (s, 2H), 4.80 (s, 2H) 7.20 (d, 2H), 7.36 (d, 2H), 7.59 (s, 1H), 7.78 (s, 1H). GC-MS: m/z 409 (M)+, 388 (M−21)+.
Reaction SMILES: C([N:9]1[C:14](=[O:15])[CH:13]=[CH:12][N:11]([CH2:16]/[CH:17]=[CH:18]\[CH2:19][O:20][C:21]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:10]1=[O:40])(=O)C1C=CC=CC=1.C(Cl)Cl.CO>CO[Na].CO>[C:21]([O:20][CH2:19][CH:18]=[CH:17][CH2:16][N:11]1[CH:12]=[CH:13][C:14](=[O:15])[NH:9][C:10]1=[O:40])([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)([C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1
Reactant: O=C(c1ccccc1)n1c(=O)ccn(C/C=C\COC(c2ccccc2)(c2ccccc2)c2ccccc2)c1=O
Agent: CO[Na]
Solvent: ClCCl
Solvent: CO
Product: O=c1ccn(CC=CCOC(c2ccccc2)(c2ccccc2)c2ccccc2)c(=O)[nH]1
Temperature: 25 °C
Reaction time: 24 h
Yield: 94.2 %

Procedure:
A suspension of compound (2) (50 mg; 0.095 mmol) in MeONa/MeOH 0.2 M (5 ml) was stirred at room temperature for 24 hours. During such period of time the suspension became a colourless solution and the TLC (DCM/MeOH 90:10) showed the complete disappearance of the starting amide, and the presence of a new spot at lower Rf. The solution was neutralised with Dowex ion exchange resin. The resin was filtered off and washed twice with MeOH (5 ml). The filtrate was concentrated under reduced pressure and purified by flash chromatography using MeOH/DCM 10:90 as eluent which gave the title compound as a white solid (38 mg, 90%). Rf: 0.66 in DCM/MeOH 90:10.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([Cl:11])[C:3]=1[CH:4]=[N:5][OH:6].ClN1C(=O)CCC1=O.[CH:20]1([C:24](=O)[CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:23][CH2:22][CH2:21]1.[O-]CC.[Na+].C(O)C>CN(C=O)C.O1CCCC1.O>[CH:20]1([C:24]2[O:6][N:5]=[C:4]([C:3]3[C:2]([Cl:1])=[CH:10][CH:9]=[CH:8][C:7]=3[Cl:11])[C:25]=2[C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:21][CH2:22][CH2:23]1
Reactant: CCOC(=O)CC(=O)C1CCC1
Reactant: ON=Cc1c(Cl)cccc1Cl
Agent: CC[O-]
Agent: O=C1CCC(=O)N1Cl
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCO
Solvent: CN(C)C=O
Product: CCOC(=O)c1c(-c2c(Cl)cccc2Cl)noc1C1CCC1
Reaction time: 1 h
Yield: 38 %

Procedure:
To a solution of 2,6-dichlorobenzaldehyde oxime (2.2 g, 11.6 mmol) in N,N,-dimethylformamide (7 mL) cooled in a water bath was added solid N-chlorosuccinimide (1.5 g, 11.6 mmol). The solution was stirred with the flask in the water bath for approximately 20 minutes and then with the flask out of the bath for approximately 1 hour. The solution was poured into water and then extracted twice with ether. The combined organic phases were dried over magnesium sulfate and concentrated. To a separate solution of ethyl 3-cyclobutyl-3-oxopropanoate (2.4 g, 13.9 mmol) in tetrahydrofuran (3 mL) at 0° C. was added a 3.16 M solution of sodium ethoxide in ethanol (4.4 mL, 13.9 mmol) quickly. The solution was stirred for a few minutes. To that solution was added the isolated imidoyl chloride in tetrahydrofuran (5 mL) dropwise. The solution was stirred at 0° C. for approximately 1 h and then allowed to stir at ambient temperature overnight. The solution was poured into water and extracted with ethyl acetate. The combined organic phases were dried over magnesium sulfate, concentrated and purified by chromatography (silica gel, 0-5% ethyl acetate in hexanes gradient elution) to afford a white solid (1.5 g, 38%). 1H-NMR (DMSO-d6) 7.63-7.53 (m, 3H), 4.25 (quintet, J=9 Hz, 1H), 4.02 (q, J=7 Hz, 2H), 2.43-2.36 (m, 4H), 2.15-1.89 (m, 2H), 0.94 (t, J=7 Hz, 3H).
Reaction SMILES: [CH:1]1([C:7]([OH:9])=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1>C1(C)C=CC=CC=1>[C:7]([OH:9])(=[O:8])[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C(O)C1CCCCC1
Solvent: Cc1ccccc1
Product: O=C(O)c1ccccc1

Procedure:
cyclohexanecarboxylic acid process in which toluene is oxidized in air to produce benzoic acid, the produced benzoic acid is hydrogenated to produce cyclohexanecarboxylic acid, and the produced cyclohexanecarboxylic acid is reacted with nitrosylsulfuric acid in the presence of fuming sulfuric acid, to thereby obtain ε-caprolactam;