Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(C1C=CC(C)=CC=1)(C)(C)C.ON1C(=O)N(O)C(=O)N(O)C1=O.O=O.[C:26]([C:30]1[CH:38]=[CH:37][C:33]([C:34](O)=[O:35])=[CH:32][CH:31]=1)([CH3:29])([CH3:28])[CH3:27]>C(O)(=O)C>[C:26]([C:30]1[CH:31]=[CH:32][C:33]([CH:34]=[O:35])=[CH:37][CH:38]=1)([CH3:29])([CH3:27])[CH3:28]
Reactant: CC(C)(C)c1ccc(C(=O)O)cc1
Agent: Cc1ccc(C(C)(C)C)cc1
Agent: O=O
Agent: O=c1n(O)c(=O)n(O)c(=O)n1O
Solvent: CC(=O)O
Product: CC(C)(C)c1ccc(C=O)cc1

Procedure:
In 3 mL of acetic acid was dissolved 315 mg of p-t-butyltoluene to give a solution, and the solution was combined with 156 mg of the catalyst C and 42 mg of hexahydro-1,3,5-trihydroxy-1,3,5-triazine-2,4,6-trione (hereinafter also referred to as “THICA”), followed by stirring at 100° C. in an oxygen atmosphere for 6 hours. The reaction mixture was analyzed through gas chromatography to find that p-t-butylbenzoic acid and p-t-butylbenzaldehyde were produced in yields of 84.5% and 1.4%, respectively, with a conversion from p-t-butyltoluene of 99.7%. The catalyst C was separated from the reaction mixture through filtration, washed with ethyl acetate two times, dried at room temperature (25° C.) under reduced pressure, and thereby recovered as a catalyst C1.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[CH:8]=[N:7][C:6]([NH2:13])=[CH:5]2.[C:14](N1C=CC=CC1=O)(N1C=CC=CC1=O)=[S:15]>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:12])[CH:11]=1)[CH:8]=[N:7][C:6]([N:13]=[C:14]=[S:15])=[CH:5]2
Reactant: O=c1ccccn1C(=S)n1ccccc1=O
Reactant: Nc1cc2cc(Cl)cc(Cl)c2cn1
Solvent: ClCCl
Product: S=C=Nc1cc2cc(Cl)cc(Cl)c2cn1
Temperature: 40 °C
Reaction time: 4 h
Yield: 60.9 %

Procedure:
To 6,8-dichloroisoquinolin-3-amine (0.27 g, 1.28 mmol) in dichloromethane (20 mL) was added 1,1′-thiocarbonyldipyridin-2(1H)-one (0.30 g, 1.29 mmol) and the reaction mixture was stirred at 40° C. for 4 hours. The reaction was cooled to room temperature and chromatographed (Biotage: 10-100% ethyl acetate/hexanes) to yield 6,8-dichloro-3-isothiocyanatoisoquinoline (0.2 g, 0.78 mmol, 61.9% yield) as a powder. 1H NMR (500 MHz, DMSO-D6) δ ppm 9.42 (s, 1H), 8.16 (d, J=1.83 Hz, 1H), 8.02 (d, J=2.14 Hz, 1H), 7.92 (s, 1H). MS (LC/MS) R.T.=3.63; [M+H]+=255.0.
Reaction SMILES: [C:1]1([CH2:9][OH:10])[C:2]([CH2:7][OH:8])=[CH:3][CH:4]=[CH:5][CH:6]=1.C1(C)C=CC=CC=1.[O:18]1[CH:23]=[CH:22][CH2:21][CH2:20][CH2:19]1>>[O:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH:19]1[O:8][CH2:7][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=1[CH2:9][OH:10]
Reactant: C1=COCCC1
Reactant: OCc1ccccc1CO
Solvent: Cc1ccccc1
Product: OCc1ccccc1COC1CCCCO1
Temperature: 30 °C
Reaction time: 5 h

Procedure:
To a suspension of 1,2-benzenedimethanol (5 g, 36.19 mmol) in toluene/2,3-dihydropyran (206 ml/11 ml) at 30° C. was added 3.62 g Dowex (50WX2-100). The reaction stirred at 30° C. for 5 hours. The mixture was filtered to remove Dowex, then concentrated in vacuo and put on vacuum pump overnight w/stirring to remove 2,3-dihydropyran. The crude reaction product was purified by normal phase chromatography (20% EtOAc/hexanes—25% -30%) to give a clear liquid (5.72 g).
Reaction SMILES: C([Li])CCC.[CH3:6][C:7]1[S:8][CH:9]=[CH:10][C:11]=1[CH3:12].[CH:13](=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[Cl-].[NH4+]>C1COCC1>[CH3:12][C:11]1[CH:10]=[C:9]([CH:13]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[OH:20])[S:8][C:7]=1[CH3:6]
Reactant: O=Cc1ccccc1
Reactant: Cc1ccsc1C
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: C1CCOC1
Product: Cc1cc(C(O)c2ccccc2)sc1C
Temperature: 0 °C
Reaction time: 0.75 h
Yield: 79.8 %

Procedure:
n-Butyl lithium (19.6 ml, 49.1 mmol, 2.5 N in hexanes) was added dropwise to a stirred solution of 2,3-dimethyl-thiophene (5.0 g, 44.6 mmol) in THF (100 mL) at −78° C. under a dry nitrogen atmosphere. The solution was warmed to 0° C. for 30 min and recooled to −78° C. whereupon benzaldehyde (5.0 mL, 49.1 mmol ) was added. After an additional 45 minutes, sat. aq. ammonium chloride was added and the reaction mixture was partitioned between water and ether. The ether phase was washed with brine and concentrated. The resultant oil was triturated with pet. ether to provide the title compound as a white solid (7.77 g, 80%): mp 80-81° C.: NMR (CDCl3); δ7.45 (ddd, J=8, 1, 1 Hz, 2H), 7.37 (ddd, J=8, 8, 1 Hz, 2H), 7.3 (m, 1H), 6.57 (s, 1H), 6.93 (s, 1H, OH), 2.29 (s, 3H), 2.05 (s, 3H); MS (EI) (M+) 218 (45%, MI): Anal. Calc. for C13H14OS: C, 71.52; H, 6.46; N, 0.00. Found: C, 71.41; H, 6.42; N, 0.09.
Reaction SMILES: Cl.[NH2:2][CH2:3][C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[C:6](=[O:23])[N:7]([CH:15]1[CH2:20][CH2:19][C:18](=[O:21])[NH:17][C:16]1=[O:22])[C:8]([CH3:14])=[N:9]2.[F:24][C:25]1[CH:26]=[C:27]([CH:31]=[CH:32][CH:33]=1)[C:28](Cl)=[O:29].C(N(CC)C(C)C)(C)C>C(#N)C>[O:22]=[C:16]1[CH:15]([N:7]2[C:6](=[O:23])[C:5]3[C:10](=[CH:11][CH:12]=[CH:13][C:4]=3[CH2:3][NH:2][C:28](=[O:29])[C:27]3[CH:31]=[CH:32][CH:33]=[C:25]([F:24])[CH:26]=3)[N:9]=[C:8]2[CH3:14])[CH2:20][CH2:19][C:18](=[O:21])[NH:17]1
Reactant: O=C(Cl)c1cccc(F)c1
Reactant: Cc1nc2cccc(CN)c2c(=O)n1C1CCC(=O)NC1=O
Agent: Cl
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: Cc1nc2cccc(CNC(=O)c3cccc(F)c3)c2c(=O)n1C1CCC(=O)NC1=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 38.9 %

Procedure:
To a stirred mixture of 3-(5-aminomethyl-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione hydrogen chloride (0.47 g, 1.4 mmol) in acetonitrile (10 mL), was added 3-fluoro-benzoyl chloride (0.25 mL, 2.1 mmol) and N,N-diisopropyl ethylamine (0.61 mL, 3.5 mmol). The mixture was stirred at room temp overnight. The solvent was evaporated, and the residue was purified by flash column chromatography (Silica gel, methanol/methylene chloride 4%/96%) to give N-[3-(2,6-dioxo-piperidin-3-yl)-2-methyl-4-oxo-3,4-dihydro-quinazolin-5-ylmethyl]-3-fluoro-benzamide as a white solid (230 mg, 40% yield); HPLC, Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 10/90 CH3CN/0.1% H3PO4, gradient to 95/5 in 5 min, kept for 5 min, 5.80 min (98.8%); mp, 240-242° C.; 1HNMR (DMSO-d6) 2.18-2.24 (m, 1H, CHH), 2.59-2.93 (m, 6H, CHCH2, CH3), 4.93-5.10 (m, 2H, CH2NH), 5.28 (dd, J=6, 11 Hz, 1H, CH), 7.36-7.80 (m, 7H, Ar), 9.08 (t, 1H, J=6 Hz, CH2NH), 11.06 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.79, 23.07, 30.58, 42.16, 56.58, 113.94, 114.24, 117.52, 118.09, 118.36, 123.38, 123.41, 124.16, 124.99, 130.52, 130.62, 134.12, 136.52, 136.61, 140.79, 147.84, 155.29, 160.39, 160.90, 163.62, 164.99, 165.02, 169.45, 172.60. LCMS MH=423; Anal Calcd For C22H19N4O4F+0.4H2O: C, 61.51; H, 4.65; N, 13.04; F, 4.42. Found: C, 61.32; H, 4.44; N, 12.97; F, 4.27.
Reaction SMILES: [CH3:1][S:2][CH2:3][CH2:4][C@@H:5]([OH:8])[CH2:6][OH:7].[C:9]1([CH3:19])[CH:14]=[CH:13][C:12]([S:15](Cl)(=[O:17])=[O:16])=[CH:11][CH:10]=1>N1C=CC=CC=1>[C:9]1([CH3:19])[CH:14]=[CH:13][C:12]([S:15]([O:7][CH2:6][C@H:5]([O:8][S:15]([C:12]2[CH:13]=[CH:14][C:9]([CH3:19])=[CH:10][CH:11]=2)(=[O:17])=[O:16])[CH2:4][CH2:3][S:2][CH3:1])(=[O:17])=[O:16])=[CH:11][CH:10]=1
Reactant: CSCC[C@@H](O)CO
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: c1ccncc1
Product: CSCC[C@H](COS(=O)(=O)c1ccc(C)cc1)OS(=O)(=O)c1ccc(C)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
(R)-4-(Methylthio)-1,2-butanediol (0.4 g, 2.9 mmol) was dissolved in 5 ml of pyridine and cooled to 0°-5° C. p-Toluenesulfonyl chloride (1.65 g, 9.0 mmol) was added and, after 5 minutes, the cooling bath removed, and the mixture stirred at room temperature for 2 hours, at which point it was diluted with 15 ml of H2O and extracted with 20 ml of ethyl acetate. The organic extract was washed with saturated NaCl, dried (MgSO4) and stripped to yield 0.5 g of present, crude title product as an oil, all of which was used in the next step without further refinement; tlc Rf 0.53 (3:1 hexane:ethyl acetate), 0.25 (5:1 hexane:ethyl acetate).
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[C:10]([F:12])[C:9]([CH3:13])=[C:8]2[C:3]=1[C:4](=[O:23])[C:5]([C:18]([O:20]CC)=[O:19])=[CH:6][N:7]2[C@@H:14]1[CH2:16][C@@H:15]1[F:17].O.S(=O)(=O)(O)O>C(O)(=O)C>[NH2:1][C:2]1[CH:11]=[C:10]([F:12])[C:9]([CH3:13])=[C:8]2[C:3]=1[C:4](=[O:23])[C:5]([C:18]([OH:20])=[O:19])=[CH:6][N:7]2[C@@H:14]1[CH2:16][C@@H:15]1[F:17]
Reactant: CCOC(=O)c1cn([C@@H]2C[C@@H]2F)c2c(C)c(F)cc(N)c2c1=O
Agent: O=S(=O)(O)O
Solvent: CC(=O)O
Solvent: O
Product: Cc1c(F)cc(N)c2c(=O)c(C(=O)O)cn([C@@H]3C[C@@H]3F)c12
Temperature: 120 °C
Reaction time: 4 h
Yield: 82.3 %

Procedure:
Ethyl 5-amino-7-fluoro-1-[2-(S)-fluoro-1-(R)-cyclopropyl]-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylate (735 mg, 2.28 mmol) was dissolved in a 1:1 mixed solution (8 ml) of acetic acid:water, and after adding concentrated sulfuric acid (90 μl) thereto, it was stirred for 4 hours in an oil bath of 120° C. After cooling the reaction solution with ice, water (20 ml) was poured therein, and the mixed reaction solution was stirred at room temperature for 2 hours. The precipitated crystals were filtered out, washed with excess water, a small amount of cold ethanol and excess diethyl ether in that order, and then dried under a reduced pressure at 80° C. for 17 hours. 552 mg (82%) of the title compound was thereby obtained in the form of yellow crystals.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([O:7][C:8](=[O:22])[NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:3][CH2:2]1.[O:23]1[CH2:27][CH2:26][O:25][CH:24]1[C:28]1[C:33]([CH3:34])=[CH:32][C:31]([NH:35][C:36](=[O:39])[CH:37]=[CH2:38])=[C:30]([CH3:40])[CH:29]=1.ClCCl>C(O)C>[O:23]1[CH2:27][CH2:26][O:25][CH:24]1[C:28]1[C:33]([CH3:34])=[CH:32][C:31]([NH:35][C:36]([CH2:37][CH2:38][N:1]2[CH2:2][CH2:3][CH:4]([O:7][C:8](=[O:22])[NH:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:5][CH2:6]2)=[O:39])=[C:30]([CH3:40])[CH:29]=1
Reactant: O=C(Nc1ccccc1-c1ccccc1)OC1CCNCC1
Reactant: C=CC(=O)Nc1cc(C)c(C2OCCO2)cc1C
Solvent: CCO
Solvent: ClCCl
Product: Cc1cc(C2OCCO2)c(C)cc1NC(=O)CCN1CCC(OC(=O)Nc2ccccc2-c2ccccc2)CC1
Temperature: 25 °C
Yield: 82.8 %

Procedure:
To a 500 mL round-bottom flask was added biphenyl-2-ylcarbamic acid piperidin-4-yl ester (17.0 g, 58 mmol) and N-(4-[1,3]dioxolan-2-yl-2,5-dimethylphenyl)acrylamide (13.1 g, 52.9 mmol). Ethanol (150 mL) and dicloromethane (150 mL) were added to form a slurry. The reaction mixture was heated at 50° C. to 55° C. for about 24 hours and then cooled to room temperature. Most of the solvent was removed on a rotary evaporator, resulting in a thick slurry. Ethanol (reagent grade) was added to form a total volume of about 200 mL and the resulting mixture was heated to 80° C. and then cooled slowly to room temperature. The resulting thick white slurry was filtered, washed with ethanol (20 mL) and dried in vacuum to provide biphenyl-2-ylcarbamic acid 1-[2-(4-[1,3]dioxolan-2-yl-2,5-dimethylphenylcarbamoyl)ethyl]piperidin-4-yl ester (23.8 g, about 98% purity) as a white solid.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[C:7]1([CH3:25])[CH:12]=[CH:11][C:10]([N:13]2[C:17]3([CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)[C:16](=[O:23])[NH:15][C:14]2=[O:24])=[CH:9][CH:8]=1.Br[CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29].O>CN(C=O)C>[CH2:31]([O:30][C:28](=[O:29])[CH2:27][N:15]1[C:16](=[O:23])[C:17]2([CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[N:13]([C:10]2[CH:9]=[CH:8][C:7]([CH3:25])=[CH:12][CH:11]=2)[C:14]1=[O:24])[CH3:32]
Reactant: CCOC(=O)CBr
Reactant: Cc1ccc(N2C(=O)NC(=O)C23CCCCC3)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)CN1C(=O)N(c2ccc(C)cc2)C2(CCCCC2)C1=O
Temperature: 25 °C
Reaction time: 18 h

Procedure:
17.9 g (0.130 mol; 1.1 eq.) of potassium carbonate are added to a solution of 30.4 g (0.117 mol; 1 eq.) of 1-p-tolyl-1,3-diazaspiro[4.5]decane-2,4-dione in 150 ml of DMF, and 16 ml (0.141 mol; 1.2 eq.) of ethyl bromoacetate are then added dropwise to the reaction medium. The cream-coloured reaction medium suspension is stirred at room temperature for 18 hours. The reaction medium is poured into 300 ml of water and the white precipitate is filtered off, rinsed with water and then dried in an oven under vacuum at 40° C. for 48 hours. The product (2,4-dioxo-1-p-tolyl-1,3-diaza-spiro[4.5]dec-3-yl)acetic acid ethyl ester is obtained in the form of a white solid.
Reaction SMILES: [CH3:1][N+:2]1([CH3:9])[CH2:7][CH2:6][CH:5]([SH:8])[CH2:4][CH2:3]1.[OH:10][C@@H:11]([C@H:13]1[C:33](=[O:34])[N:15]2[CH:16]([C:20]([O:22]CC3C=CC([N+]([O-])=O)=CC=3)=[O:21])[C:17](=O)[CH2:18][C@H:14]12)[CH3:12]>>[CH3:1][N+:2]1([CH3:9])[CH2:7][CH2:6][CH:5]([S:8][C:17]2[CH2:18][C@@H:14]3[C@@H:13]([C@H:11]([OH:10])[CH3:12])[C:33](=[O:34])[N:15]3[C:16]=2[C:20]([O-:22])=[O:21])[CH2:4][CH2:3]1
Reactant: C[N+]1(C)CCC(S)CC1
Reactant: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)C(=O)C[C@H]12
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)[O-])=C(SC3CC[N+](C)(C)CC3)C[C@H]12
Yield: 6.8 %

Procedure:
Following a procedure similar to that described in Example 6, but using 368 mg of the crude 1,1-dimethyl-4-mercaptopiperidinium salt prepared as described in Example 7-(1) and, 363 mg of 4-nitrobenzyl (5R, 6S)-6-[(1R)-1-hydroxyethyl]-2-oxo-1-carbapenam-3-carboxylate, 24 mg of the title compound were obtained.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH2:8]O)[CH:5]=[N:6][CH:7]=1.C1(P([N:24]=[N+:25]=[N-:26])(C2C=CC=CC=2)=O)C=CC=CC=1.N12CCCN=C1CCCCC2>C1COCC1>[N:24]([CH2:8][C:4]1[CH:5]=[N:6][CH:7]=[C:2]([Br:1])[CH:3]=1)=[N+:25]=[N-:26]
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Reactant: OCc1cncc(Br)c1
Solvent: C1CCOC1
Solvent: C1CCC2=NCCCN2CC1
Product: [N-]=[N+]=NCc1cncc(Br)c1
Reaction time: 8 h
Yield: 93.3 %

Procedure:
To a solution of (5-bromo-pyridin-3-yl)-methanol 249 (1.4 g, 7.5 mmol, 1.00 equiv) and diphenylphosphoryl azide (2.4 mL, 9.0 mmol, 1.2 equiv) in THF (15 mL) at it was added 1,8-diazabicyclo[5.4.0]undec-7-ene (1.4 mL, 9.0 mmol, 1.2 equiv). The resulting solution was stirred overnight, concentrated and chromatographically purified (15% ethyl acetate in hexanes) to give 3-azidomethyl-5-bromo-pyridine 250 (1.49 g). LCMS (MH)+=212.9, rt=1.50 min.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][C:22]=1[C:23]([N:25]1[CH2:29][CH2:28][CH2:27][CH:26]1[CH2:30][CH2:31][C:32]([OH:34])=O)=[O:24])[C:5]([NH:7][C@H:8]([C:10]1[NH:14][C:13]2[CH:15]=[CH:16][C:17]([Cl:19])=[CH:18][C:12]=2[N:11]=1)[CH3:9])=[O:6].CN(C(O[N:43]1N=NC2C=[CH:47][CH:48]=[CH:49][C:44]1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(C(C)C)CC)(C)C.N1CCCC1.ClCl>O1CCCC1.ClCCl.C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:20]=[CH:21][C:22]=1[C:23]([N:25]1[CH2:29][CH2:28][CH2:27][CH:26]1[CH2:30][CH2:31][C:32]([N:43]1[CH2:44][CH2:49][CH2:48][CH2:47]1)=[O:34])=[O:24])[C:5]([NH:7][C@H:8]([C:10]1[NH:14][C:13]2[CH:15]=[CH:16][C:17]([Cl:19])=[CH:18][C:12]=2[N:11]=1)[CH3:9])=[O:6]
Reactant: C[C@H](NC(=O)c1ccc(C(=O)N2CCCC2CCC(=O)O)c(Cl)c1)c1nc2cc(Cl)ccc2[nH]1
Reactant: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: ClCl
Agent: F[B-](F)(F)F
Solvent: C1CCNC1
Solvent: CCN(C(C)C)C(C)C
Solvent: CCO
Product: C[C@H](NC(=O)c1ccc(C(=O)N2CCCC2CCC(=O)N2CCCC2)c(Cl)c1)c1nc2cc(Cl)ccc2[nH]1
Yield: 22 %

Procedure:
Prepared analogously to Example 1g from 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-[(2R/S)-2-(hydroxycarbonylethyl)pyrrolidin-1-ylcarbonyl]benzamide, TBTU, diisopropylethylamine, and pyrrolidine in tetrahydrofuran. Yield: 22%; Rf value: 0.53 (silica gel: dichloromethane/ethanol=9:1); C28H31Cl2N5O3 (556.497); mass spectrum: (M+H)+=556/558/560 (chlorine isotope).
Reaction SMILES: [O:1]=[C:2]1[CH:8]([CH2:9][C:10]([O:12]C)=[O:11])[CH2:7][C:6]2[CH:14]=[CH:15][C:16]([O:18][CH2:19][CH2:20][CH2:21][N:22]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=3)[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[CH:17][C:5]=2[CH2:4][N:3]1[CH2:36][C:37]1[CH:42]=[CH:41][C:40]([C:43]([F:46])([F:45])[F:44])=[CH:39][CH:38]=1.N1C=CC=CC=1NCCCOC1C=CC2CC(CC(OCC)=O)C(=O)NCC=2C=1>O>[O:1]=[C:2]1[CH:8]([CH2:9][C:10]([OH:12])=[O:11])[CH2:7][C:6]2[CH:14]=[CH:15][C:16]([O:18][CH2:19][CH2:20][CH2:21][N:22]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=3)[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[CH:17][C:5]=2[CH2:4][N:3]1[CH2:36][C:37]1[CH:42]=[CH:41][C:40]([C:43]([F:46])([F:44])[F:45])=[CH:39][CH:38]=1
Reactant: COC(=O)CC1Cc2ccc(OCCCN(C(=O)OC(C)(C)C)c3ccccn3)cc2CN(Cc2ccc(C(F)(F)F)cc2)C1=O
Agent: CCOC(=O)CC1Cc2ccc(OCCCNc3ccccn3)cc2CNC1=O
Solvent: O
Product: CC(C)(C)OC(=O)N(CCCOc1ccc2c(c1)CN(Cc1ccc(C(F)(F)F)cc1)C(=O)C(CC(=O)O)C2)c1ccccn1

Procedure:
According to the procedure of Example 1(c), except substituting methyl (±)-3-oxo8-[3-[N-(pyridin-2-yl)-N-(tert-butoxycarbonyl)amino]-1-propyloxy]-2-(4-trifluoromethylbenzyl)-2,3,4,5-tetrahydro-1H-2-benzazepine-4-acetate for the ethyl (±)-8-[3-(2-pyridylamino)-1-propyloxy]-3-oxo-2,3,4,5-tetrahydro-1H-2-benzazepine-4-acetate, the title compound was prepared as an off-white solid: MS (ES) m/e 628.4 (M+H)+. Anal. Calcd for C33H36F3N3O6.0.5 H2O: C, 62.25; H, 5.86; N, 6.60. Found C, 62.01; H, 5.92; N, 6.81.
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[C:5]([NH:7][CH2:8]/[CH:9]=[CH:10]/[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:6].[CH2:20](N)[CH:21]=[CH:22][C:23]1C=CC=CC=1.C1C2C(=CC=CC=2)C=CC=1C(O)=O>>[CH2:8]([NH:7][C:5]([C:4]1[CH:17]=[CH:18][C:19]2[C:2](=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:3]=1)=[O:6])/[CH:9]=[CH:10]/[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: NCC=Cc1ccccc1
Reactant: O=C(NC/C=C/c1ccccc1)c1cccc(Cl)c1
Agent: O=C(O)c1ccc2ccccc2c1
Product: O=C(NC/C=C/c1ccccc1)c1ccc2ccccc2c1

Procedure:
(E)-N-Cinnamyl-2-naphthalenecarboxamide may be obtained in the following manner: working in a manner similar to that described in Example 21 for the preparation of (E)-3-chloro-N-cinnamylbenzamide, starting with cinnamylamine (5.3 g) and 2-naphthoic acid (7.6 g), and after recrystallization in ethyl acetate, (E)-N-cinnamyl-2-naphthalenecarboxamide (4.3 g) is obtained.
Reaction SMILES: [NH2:1][C:2]1[N:10]=[C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[CH:17][CH:18]=3)[N:13]([CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[F:27])[N:12]=2)[N:8]=[C:7]2[C:3]=1[NH:4][C:5](=[O:28])[NH:6]2.CCN(P1(N(C)CCCN1C)=NC(C)(C)C)CC.ClC(Cl)(Cl)S(O[CH2:53][C:54]([F:57])([F:56])[F:55])(=O)=O>CN(C)C=O>[NH2:1][C:2]1[N:10]=[C:9]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[CH:17][CH:18]=3)[N:13]([CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[F:27])[N:12]=2)[N:8]=[C:7]2[C:3]=1[NH:4][C:5](=[O:28])[N:6]2[CH2:53][C:54]([F:57])([F:56])[F:55]
Reactant: O=S(=O)(OCC(F)(F)F)C(Cl)(Cl)Cl
Reactant: Nc1nc(-c2nn(Cc3ccccc3F)c3ncccc23)nc2[nH]c(=O)[nH]c12
Agent: CCN(CC)P1(=NC(C)(C)C)N(C)CCCN1C
Solvent: CN(C)C=O
Product: Nc1nc(-c2nn(Cc3ccccc3F)c3ncccc23)nc2c1[nH]c(=O)n2CC(F)(F)F
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 49.2 %

Procedure:
100 mg (0.266 mmol) of the compound from example 33 and 73 mg (0.266 mmol) of BEMP were initially charged in 9 ml of dimethylformamide, and a solution of 75 mg (0.266 mmol) of 2,2,2-trifluoroethyl trichloromethanesulfonate in 1 ml of dimethylformamide was added dropwise at 0° C. within 10 min. The mixture was stirred at 0° C. for 20 min. Subsequently, the reaction solution was concentrated under reduced pressure and the residue was purified by means of preparative HPLC (eluent: methanol/water, gradient 30:70→90:10). 60 mg of the title compound were obtained (47% of theory).
Reaction SMILES: [CH3:1][N:2]([CH3:18])[C:3](=O)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[S:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.CNC(=O)C1C=CC=CC=1SC1C=CC=CC=1>>[CH3:18][N:2]([CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[S:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:1]
Reactant: CN(C)C(=O)c1ccccc1Sc1ccccc1
Agent: CNC(=O)c1ccccc1Sc1ccccc1
Product: CN(C)Cc1ccccc1Sc1ccccc1

Procedure:
By following essentially the same procedure described in Example 2 but substituting N,N-dimethyl-2-(phenylthio)benzamide for the N-methyl-2-(phenylthio)benzamide, there is obtained N,N-dimethyl-2-(phenylthio)benzylamine.
Reaction SMILES: C1(N=C=NC2CCCCC2)CCCCC1.OC1C2N=NNC=2C=CC=1.[CH3:26][O:27][C:28](=[O:34])[CH2:29][CH2:30][C:31]([O-])=O.[NH2:35][C:36]1[CH:37]=[C:38]([C:43]2[CH:50]=[CH:49][CH:48]=[CH:47][C:44]=2[C:45]#[N:46])[CH:39]=[CH:40][C:41]=1[NH2:42]>CN(C=O)C>[C:45]([C:44]1[CH:47]=[CH:48][CH:49]=[CH:50][C:43]=1[C:38]1[CH:39]=[CH:40][C:41]2[NH:42][C:31]([CH2:30][CH2:29][C:28]([O:27][CH3:26])=[O:34])=[N:35][C:36]=2[CH:37]=1)#[N:46]
Reactant: COC(=O)CCC(=O)[O-]
Reactant: N#Cc1ccccc1-c1ccc(N)c(N)c1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Oc1cccc2[nH]nnc12
Solvent: CN(C)C=O
Product: COC(=O)CCc1nc2cc(-c3ccccc3C#N)ccc2[nH]1
Temperature: 25 °C
Reaction time: 48 h
Yield: 75.3 %

Procedure:
Dicyclohexylcarbodiimide (0.11 moles, 2.26 g), hydroxybenzotriazole, (0.011 moles, 1.48 g) and monomethylsuccinate (0.011 moles, 1.45 g) were dissolved in 75 ml of DMF. 2-(3,4-Diaminophenyl)benzonitrile (0.01 moles, 2.0 g) was added. The reaction was stirred at room temperature for 48 hours The solvent was removed in vacuo. The residue was dissolved in ethyl acetate and washed thoroughly with brine. The ethyl acetate solution was dried over sodium sulfate and filtered. The solvent was removed. The residue was purified by HPLC on silica gel eluted with ethyl acetate. The material was dissolved in 400 ml toluene with 5 mg of p-toluenesulfonic acid and refluxed for 8 hours. The solvent was removed. The residue was purified by HPLC on silica gel eluted with ethyl acetate to yield 2.3 g of methyl 3-[5-(2-cyanophenyl)-1H-benzimidazole-2-yl]propionate. (MS).
Reaction SMILES: [CH3:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([CH:9]=O)=[CH:4][N:3]=1.S(O)(O)(=O)=O.[NH2:16][OH:17]>CO.O>[CH3:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([CH:9]=[N:16][OH:17])=[CH:4][N:3]=1
Reactant: Cc1ncc(C=O)c(N)n1
Reactant: NO
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CO
Product: Cc1ncc(C=NO)c(N)n1
Yield: 148.3 %

Procedure:
To 8.6 g of 2-methyl-4-amino-5-formylpyrimidine, while stirring at room temperature in a mixture of 340 ml of methanol and 40 ml of water, was added dropwise gradually 10 ml of an aqueous solution containing 6.10 g of hydroxylamine sulfate. As the reaction proceeded, crystals precipitated out. Four hours later, the crystals were collected by filtration, followed by drying under reduced pressure to give 10.5 g (83.5%) of 2-methyl-4-amino-5-pyrimidine aldoxime 1/2 sulfate. The mother liquor was subjected to quantitative deterimination (by absolute calibration curve method) of 2-methyl-4-amino-5-pyrimidine aldoxime 1/2 sulfate by means of high performance liquid chromatography to thereby confirm the production of 1.67 g (13.3%) of the object compound. The total yield of the crystals thus obtained and the object compound in the mother liquor was 96.8%. Physical properties of 2-methyl-4-amino-5-pyrimidine aldoxime 1/2 sulfate first obtained were as follows:
Reaction SMILES: [CH3:1][C:2]1([CH3:21])[C:11]2[C:6](=[CH:7][C:8]([CH:12]([CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[C:13]([OH:15])=[O:14])=[CH:9][CH:10]=2)[O:5][CH2:4][CH2:3]1.O[C:23]1[CH:38]=[CH:37][C:26]([C:27]([O:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[O:28])=[CH:25][CH:24]=1.C1CCC(N=C=NC2CCCCC2)CC1>ClCCl.CN(C1C=CN=CC=1)C>[CH2:30]([O:29][C:27](=[O:28])[C:26]1[CH:37]=[CH:38][C:23]([O:14][C:13](=[O:15])[CH:12]([C:8]2[CH:7]=[C:6]3[C:11]([C:2]([CH3:21])([CH3:1])[CH2:3][CH2:4][O:5]3)=[CH:10][CH:9]=2)[CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])=[CH:24][CH:25]=1)[C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=1
Reactant: CCCCCC(C(=O)O)c1ccc2c(c1)OCCC2(C)C
Reactant: O=C(OCc1ccccc1)c1ccc(O)cc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: CCCCCC(C(=O)Oc1ccc(C(=O)OCc2ccccc2)cc1)c1ccc2c(c1)OCCC2(C)C
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 84.3 %

Procedure:
A solution of 2-(4,4-dimethyl-chroman-7-yl)-heptanoic acid (105 mg, 0.36 mmol) in 5 mL of dichloromethane with 91.6 mg, 0.4 mmol of benzyl 4-hydroxybenzoate and 44 mg, 0.36 mmol of DMAP was cooled to 0° C. and treated with 83 mg, 0.4 mmol of DCC. The mixture was kept at 0° C. for 15 minutes, then warmed to room temperature. After 2 h, the mixture was filtered and the resulting solution was washed with water and brine. The solution was dried and concentrated, then purified by flash chromatography (8% ethyl acetate/hexane) to give 152 mg (84%) of 4-[2-(4,4-dimethyl-chroman-7-yl)-heptanoyloxy]-benzoic acid benzyl ester.