Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]([C:11]1[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=1)=[O:10].[C:17]([C:21]1[CH:26]=[CH:25][C:24]([S:27](Cl)(=[O:29])=[O:28])=[CH:23][CH:22]=1)([CH3:20])([CH3:19])[CH3:18]>>[C:17]([C:21]1[CH:26]=[CH:25][C:24]([S:27]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=2[C:9]([C:11]2[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=2)=[O:10])(=[O:29])=[O:28])=[CH:23][CH:22]=1)([CH3:20])([CH3:18])[CH3:19]
Reactant: CC(C)(C)c1ccc(S(=O)(=O)Cl)cc1
Reactant: Nc1ccc(F)cc1C(=O)c1ccncc1
Product: CC(C)(C)c1ccc(S(=O)(=O)Nc2ccc(F)cc2C(=O)c2ccncc2)cc1

Procedure:
The title compound was prepared according to the general procedure for the synthesis of N-Aryl-benzenesulfonamides previously described using 108 mg of (2-Amino-5-fluoro-phenyl)-pyridin-4-yl-methanone and 116 mg of 4-tert-butyl-benzenesulfonyl chloride. 1H-NMR (400 MHz, CDCl3): δ 1.25 (s, 9H), 6.98 (dd, 1H, J=8.8 Hz, 3.2 Hz), 7.30-7.38 (m, 3H), 7.43 (m, 2H), 7.62 (m, 2H), 7.80 (dd, 1H, 9.2 Hz, 4.8 Hz), 8.82 (d, 2H, 4.8 Hz), 9.82 (s, 1H). MS: m/z413.5 (M++1).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:15])[C:4](=O)[CH:5](Cl)[C:6]1[CH:11]=[CH:10][C:9]([CH3:12])=[CH:8][CH:7]=1.[C:16]([NH2:19])(=[S:18])[CH3:17]>>[CH3:1][O:2][C:3]([C:4]1[N:19]=[C:16]([CH3:17])[S:18][C:5]=1[C:6]1[CH:11]=[CH:10][C:9]([CH3:12])=[CH:8][CH:7]=1)=[O:15]
Reactant: CC(N)=S
Reactant: COC(=O)C(=O)C(Cl)c1ccc(C)cc1
Product: COC(=O)c1nc(C)sc1-c1ccc(C)cc1

Procedure:
prepared by reaction of 3-chloro-2-oxo-3-p-tolyl-propionic acid methyl ester with thioacetamide. LC-MS: tR=0.92 min; [M+H]+=248.2.
Reaction SMILES: Cl.[C:2]([NH:6][NH2:7])([CH3:5])([CH3:4])[CH3:3].[OH-].[K+].[CH3:10][N:11]=[C:12]=[O:13]>O1CCCC1.C(Cl)(Cl)Cl>[CH3:10][NH:11][C:12]([N:6]([C:2]([CH3:5])([CH3:4])[CH3:3])[NH2:7])=[O:13]
Reactant: CC(C)(C)NN
Reactant: CN=C=O
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: ClC(Cl)Cl
Product: CNC(=O)N(N)C(C)(C)C
Reaction time: 8 h
Yield: 80 %

Procedure:
A solution of 6.23 g t-butylhydrazine hydrochloride (0.050 moles) in 50 mL tetrahydrofuran was degassed, then stirred under nitrogen as, first, one equivalent of powdered potassium hydroxide and then, dropwise, 2.85 g methyl isocyanate in 25 mL tetrahydrofuran were added. The solution was stirred overnight. The mixture was filtered to remove the residual solid impurity which was washed several times with tetrahydrofuran. The combined filtrates were evaporated to yield a white product which was taken up in chloroform and dried. Removal of the solvent yielded 5.80 g (79.9%) white crystalline N-methyl-1-t-butylhydrazinecarboxamide (m.p. 127°-9° C.). This structure was confirmed by NMR analysis.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)=O)(C)(C)C.[Cl:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH:22]=[CH:23][N+:24]([O-])=O)[CH:17]=1>C(N)C1C=CC=CC=1>[CH2:22]([N:24]1[C:11]2[CH2:10][CH2:9][NH:8][CH2:13][C:12]=2[C:22]([C:18]2[CH:19]=[CH:20][CH:21]=[C:16]([Cl:15])[CH:17]=2)=[CH:23]1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:16][CH:17]=1
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Reactant: O=[N+]([O-])C=Cc1cccc(Cl)c1
Solvent: NCc1ccccc1
Product: Clc1cccc(-c2cn(Cc3ccccc3)c3c2CNCC3)c1
Yield: 48.9 %

Procedure:
The title compound (193.3 mg) was prepared from 0.50 g of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester, 260 μL of benzylamine, and 0.45 g of 1-chloro-3-(2-nitro-vinyl)-benzene as in Example 9. MS (ESI): exact mass calculated for C20H19ClN2, 322.12; found, m/z 323.2 [M+H]+. 1H NMR (500 MHz, CDCl3): 7.36-7.20 (m, 6H), 7.14-7.07 (m, 3H), 6.81 (s, 1H), 5.01 (s, 2H), 4.04 (s, 2H), 3.14 (t, J=5.8 Hz, 2H), 2.51 (t, J=5.8 Hz, 2H).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH2:14])(=[O:13])=[O:12])=[CH:7][CH:6]=1.[CH2:15]1[O:23][C@@H:16]1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C(#N)C>[OH:23][C@H:16]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:15][NH:1][CH2:2][CH2:3][CH2:4][C:5]1[CH:6]=[CH:7][C:8]([S:11]([NH2:14])(=[O:12])=[O:13])=[CH:9][CH:10]=1
Reactant: c1ccc([C@@H]2CO2)cc1
Reactant: NCCCc1ccc(S(N)(=O)=O)cc1
Solvent: CC#N
Product: NS(=O)(=O)c1ccc(CCCNC[C@H](O)c2ccccc2)cc1
Yield: 26.6 %

Procedure:
A mixture of 20 g of 4-(3-aminopropyl)benzenesulphonamide, 16.8 g of (R)-styrene oxide and 500 ml of acetonitrile was heated under reflux for 40 hours. The solvent was then removed by evaporation in vacuo and the residue was chromatographed on 1 kg of silica gel. With chloroform/n-propanol25% ammonia (1600:100:4) there could be isolated 8.3 g of pure p-[3-[[(R)-β-hydroxyphenethyl]amino]propyl]benzenesulphonamide of melting point 165°-166° (from acetonitrile); [α]D20 =-13.4° (c=1.0% in methanol); ε224 =14710.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([C:13](OCC)=[O:14])[C@H:10]([NH:18][C:19](=[O:28])[O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Li+].[BH4-]>C1COCC1.O=[Mn]=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH:13]=[O:14])[C@H:10]([NH:18][C:19](=[O:28])[O:20][CH2:21][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CCOC(=O)[C@@H]1CN(C(=O)OC(C)(C)C)C[C@H]1NC(=O)OCc1ccccc1
Agent: O=[Mn]=O
Agent: [BH4-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1C[C@@H](C=O)[C@H](NC(=O)OCc2ccccc2)C1
Temperature: 80 °C
Reaction time: 1.5 h

Procedure:
To a solution of benzyl (3S*,4R*)-1-(tert-butoxycarbonyl)-4-(ethoxycarbonyl)pyrrolidin-3-ylcarbamate (4.4 g, 11.2 mmol) in 150 mL THF, LiBH4 (0.74 g, 33.6 mmol) was added and the mixture was stirred at 80° C. for 1.5 hours. The mixture was quenched with H2O, extracted with EtOAc, the combined organic extracts were dried with Na2SO4 and evaporated. The residue was re-dissolved in 300 mL CH2Cl2, activated MnO2 (3.86 g, 56 mmol) was added and the mixture was stirred for 24 hours at room temperature. MnO2 was filtered off through Celite, and the filtrate was evaporated giving the title aldehyde.
Reaction SMILES: [SH2:1].[C:2]([C:4]1[NH:5][C:6]([CH3:29])=[C:7]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH:8]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([N+:21]([O-:23])=[O:22])[CH:16]=2)[C:9]=1[C:10]([O:12][CH2:13][CH3:14])=[O:11])#[N:3].C(N(CC)CC)C>N1C=CC=CC=1>[NH2:3][C:2](=[S:1])[C:4]1[NH:5][C:6]([CH3:29])=[C:7]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH:8]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([N+:21]([O-:23])=[O:22])[CH:16]=2)[C:9]=1[C:10]([O:12][CH2:13][CH3:14])=[O:11]
Reactant: S
Reactant: CCOC(=O)C1=C(C)NC(C#N)=C(C(=O)OCC)C1c1cccc([N+](=O)[O-])c1
Solvent: CCN(CC)CC
Solvent: c1ccncc1
Product: CCOC(=O)C1=C(C)NC(C(N)=S)=C(C(=O)OCC)C1c1cccc([N+](=O)[O-])c1
Reaction time: 2 h

Procedure:
Hydrogen sulphide was bubbled through a solution of diethyl 2-cyano-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate (1 g, 2.6 mmoles) in triethylamine (0.36 ml, 2.6 mmoles) and pyridine (20 ml) at room temperature for 2 hours. The solution was degassed with nitrogen and poured into water (300 ml). After stirring for 2 hours, the precipitate was filtered off, dissolved in methylene chloride and dried (Na2SO4). The solvent was removed in vacuo and the residue triturated with CCl4 and filtered to give the title compound (0.5 g). M+ 419; (CDCl3) δ 9.3 (s,NH2), 5.2 (s,H).
Reaction SMILES: Cl.[CH3:2][C:3]([CH3:8])([CH3:7])[C:4]([NH2:6])=[NH:5].CN(C)[CH:11]=[C:12]([CH:22]=O)[CH:13]([CH:19]([CH3:21])[CH3:20])[C:14]([O:16][CH2:17][CH3:18])=[O:15].C(OC=C(C=O)C(C(C)C)C(OCC)=O)C.C[O-].[Na+]>C(O)C>[CH3:2][C:3]([C:4]1[N:6]=[CH:11][C:12]([CH:13]([CH:19]([CH3:20])[CH3:21])[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:22][N:5]=1)([CH3:8])[CH3:7]
Reactant: CCOC(=O)C(C(C=O)=CN(C)C)C(C)C
Reactant: CC(C)(C)C(=N)N
Agent: CCOC=C(C=O)C(C(=O)OCC)C(C)C
Agent: C[O-]
Agent: Cl
Solvent: CCO
Product: CCOC(=O)C(c1cnc(C(C)(C)C)nc1)C(C)C

Procedure:
2,2-dimethylpropionamidine hydrochloride (0.14 g), prepared according to Example 1, was added to a solution of a 4:3 mixture of ethyl (RS)-4-dimethylamino-3-formyl-2-(1-methylethyl)-3-butenoate and ethyl (RS)-4-ethoxy-3-formyl- 2-(1-methylethyl)-3-butenoate (0.2 g), prepared according to the method of Example 10, in ethanol (2 cm3). A solution of sodium methoxide (0.06 g) in ethanol (1 cm3) was added to the stirred mixture, which was then heated at the reflux temperature for 2 hours. After cooling, the ethanol was evaporated under reduced pressure. The residual oil was purified by column chromatography on a silica gel support (Merck 7729), using dichloromethane, followed by dichloromethane containing 2% by volume ethyl acetate, as eluent, to give ethyl (RS)-2-[2-(2-methylprop-2-yl)pyrimidin-5-yl]-3-methylbutyrate (0.068 g) as a pale yellow oil.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([CH3:14])[N:11]3[N:15]=[CH:16][C:17]([C:18]([OH:20])=O)=[C:10]3[N:9]=2)=[CH:4][CH:3]=1.O[NH:22][C:23](=[NH:34])[C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([S:30](=[O:33])(=[O:32])[NH2:31])[CH:25]=1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[C:12]([CH3:14])[N:11]3[N:15]=[CH:16][C:17]([C:18]4[O:20][N:34]=[C:23]([C:24]5[CH:25]=[C:26]([S:30]([NH2:31])(=[O:32])=[O:33])[CH:27]=[CH:28][CH:29]=5)[N:22]=4)=[C:10]3[N:9]=2)=[CH:6][CH:7]=1
Reactant: N=C(NO)c1cccc(S(N)(=O)=O)c1
Reactant: Cc1cc(-c2ccc(Cl)cc2)nc2c(C(=O)O)cnn12
Product: Cc1cc(-c2ccc(Cl)cc2)nc2c(-c3nc(-c4cccc(S(N)(=O)=O)c4)no3)cnn12

Procedure:
The title compound was prepared from 5-(4-chloro-phenyl)-7-methyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (example C.24) (144 mg, 0.5 mmol) and N-hydroxy-3-sulfamoyl-benzamidine [CAS-No. 9000-88-7] (161 mg, 0.75 mmol) according to general procedure II. Obtained after purification by flash chromatography (ethyl acetate/heptane) and crystallization (MeOH/dichloromethane) as a light yellow solid (70 mg, 30%). MS (EI) 466.1 [(M)+]; mp 275° C.
Reaction SMILES: [C:1]([O:7][CH2:8][CH3:9])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].[Na].[Cl:11][C:12]([Cl:16])([Cl:15])[C:13]#[N:14]>>[C:3](/[C:2](=[C:13](/[NH2:14])\[C:12]([Cl:16])([Cl:15])[Cl:11])/[C:1]([O:7][CH2:8][CH3:9])=[O:6])(=[O:4])[CH3:5]
Reactant: CCOC(=O)CC(C)=O
Reactant: N#CC(Cl)(Cl)Cl
Agent: [Na]
Product: CCOC(=O)/C(C(C)=O)=C(\N)C(Cl)(Cl)Cl
Temperature: 50 °C

Procedure:
To 130.14 g (1.00 mole) of ethyl acetoacetate was added 1.5 g of sodium. The reaction temperature increased spontaneously to 50° C. The reaction mixture was cooled with an ice bath. To the cooled reaction mixture was added, with vigorous stirring at 30°-50° C., 144.3 g (1.00 mole) of trichloroacetonitrile in 30 minutes. After complete addition of the trichloroacetonitrile, the reaction mixture was cooled with a dry ice bath. No precipitate of the ethyl 2-acetyl-3-amino-4,4,4-trichlorocrotonate formed. Part of the above product was stirred with 100 ml. of concentrated 28-30% ammonium hydroxide for 2 hours. The reaction mixture was then extracted with ether. The ether solution was dried (CaSO4) and concentrated to give 180 g (82.5%) of crude ethyl 3-amino-4,4,4-trichlorocrotonate. Part of this crude material (20 g) was distilled at 0.5 mm Hg to give 11.7 g of pure product, m.p. 91°-95° C. To a cold (10° C.) solution of 21.8 g (0.0937 mole) of crude ethyl 3-amino-4,4,4-trichlorocrotonate in 15 ml. of chlorobenzene was added 13.5 g (0.103 mole) of chlorocarbonylsulfenyl chloride. The reaction temperature rose spontaneously to 35° C. after the ice water bath was removed. The reaction mixture was stirred at 65° C. for 1 hour, cooled and triturated with petroleum ether to give 10.3 g (38%) of ethyl 2,3-dihydro-2-oxo-4-trichloromethyl-5-thiazolecarboxylate, m.p. 109°-110° C. A mixture of 14.5 g (0.05 mole) of ethyl 2,3-dihydro-2-oxo-4-trichloromethyl-5-thiazolecarboxylate, 10.4 g (0.05 mole) of phosphorus pentachloride, and 100 ml. of phosphorus oxychloride was held at reflux for 7 days. Excess phosphorus oxychloride was removed under reduced pressure. The residue was treated with ice water and the aqueous mixture was extracted with ether. The ether solution was extracted with 10% sodium hydroxide, dried (CaSO4) and concentrated under reduced pressure to give 3.2 g of oil which was chromatographed on silica gel using 5% ethyl acetate-petroleum ether as eluant. The first 1.2 l. of eluant gave 2.27 g of solid which was recrystallized from petroleum ether at low temperature to give 2.13 g (13.8%) of ethyl 2-chloro-4-trichloromethyl-5-thiazolecarboxylate, m.p. 42.5°-43.5° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[N:11]=[C:10]2[CH2:18][CH:19]2[CH2:24][CH2:23][N:22]([CH2:25][C:26]([O:28]CC)=[O:27])[CH2:21][CH2:20]2)=[CH:4][CH:3]=1.[ClH:31]>>[ClH:31].[ClH:31].[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[N:11]=[C:10]2[CH2:18][CH:19]2[CH2:24][CH2:23][N:22]([CH2:25][C:26]([OH:28])=[O:27])[CH2:21][CH2:20]2)=[CH:4][CH:3]=1
Reactant: CCOC(=O)CN1CCC(Cc2nc3ccccc3n2Cc2ccc(F)cc2)CC1
Agent: Cl
Product: O=C(O)CN1CCC(Cc2nc3ccccc3n2Cc2ccc(F)cc2)CC1
Yield: 52 %

Procedure:
A mixture of 6 parts of ethyl 4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]methyl]-1-piperidineacetate and 120 parts of a hydrochloric acid solution 6N was stirred and refluxed overnight. The reaction mixture was cooled and filtered. The filtrate was evaporated and the semi-solid residue was taken up in about 120 parts of 2-propanol. The solution was filtered and about 70 parts of 2,2'-oxybispropane were added to the filtrate. After stirring for 2 hours at room temperature, the precipitated product was filtered off, dried overnight in vacuo at 80° C. and pulverized in a mortar, yielding 3 parts (52%) of 4-[[1-[(4-fluorophenyl)methyl]-1H-benzimidazol-2-yl]methyl]-1-piperidineacetic acid dihydrochloride. monohydrate; mp. 207.4° C. (457).
Reaction SMILES: [NH:1]([C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])[C@H:2]([C:15]([OH:17])=O)[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].Cl.[NH2:29][C@H:30]([C:38]([NH:40][C@H:41]([C:49]([OH:51])=[O:50])[CH2:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)=[O:39])[CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.C(N1CCOCC1)C>CN(C)C=O>[NH:1]([C:18]([O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=[O:19])[C@H:2]([C:15]([NH:29][C@H:30]([C:38]([NH:40][C@H:41]([C:49]([OH:51])=[O:50])[CH2:42][C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1)=[O:39])[CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:17])[CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8]([O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:9]
Reactant: N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1ccccc1)C(=O)O
Reactant: CC(C)(C)OC(=O)NCCCC[C@H](NC(=O)OCc1ccccc1)C(=O)O
Agent: CCN1CCOCC1
Agent: Cl
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)NCCCC[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1ccccc1)C(=O)O
Reaction time: 24 h

Procedure:
4.19 g of Z-Lys(Boc)-OPc and 2.47 g of HCl.H-Phe-Phe-OH are taken up in 50 ml of dimethylformamide, 0.84 ml of N-ethylmorpholine are added and the whole is left to stand for 24 hours at 20°. The reaction mixture is concentrated by evaporation and the residue is triturated with water and dried over phosphorus pentoxide. Recrystallisation from ether yields crystals having a melting point of 154° to 156°.
Reaction SMILES: [C:1]1([N:7]=[C:8]=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:10](O)(=O)C.C([Sn](Cl)(Cl)CCCC)CCC>C(Cl)Cl>[C:8]([NH:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)(=[O:9])[CH3:10]
Reactant: O=C=Nc1ccccc1
Reactant: CC(=O)O
Agent: CCCC[Sn](Cl)(Cl)CCCC
Solvent: ClCCl
Product: CC(=O)Nc1ccccc1
Yield: 97 %

Procedure:
1.19 g phenyl isocyanate was reacted with 0.6 g acetic acid in a 1:1 molar ratio in the presence of dibutyltin dichloride in methylene chloride (20 parts). The molar ratio of dibutyltin dichloride to phenyl isocyanate was 1:100. The reaction, product isolation and analysis were conducted as in Example 1. A 97.0% yield of acetanilide was obtained (1.20 g).
Reaction SMILES: C=[CH:2][CH2:3][CH2:4][CH:5]([OH:12])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].[O:13]=[O+][O-].O=O.OO.[OH-].[Na+]>CO>[C:2]1(=[O:13])[O:12][CH:5]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])[CH2:4][CH2:3]1
Reactant: O=[O+][O-]
Reactant: C=CCCC(O)CCCCCC
Agent: O=O
Agent: OO
Agent: [Na+]
Solvent: CO
Product: CCCCCCC1CCC(=O)O1
Yield: 65 %

Procedure:
1-undecen-5-ol (8.5 g., 0.005 mol) dissolved in methanol (100 mL) was ozonized while being cooled in a dry ice-isopropanol bath. Upon completion of ozonolysis, excess ozone was expelled with a stream of oxygen, the ozonide was then treated with 50% H2O2 (10 ml) and 10% sodium hydroxide (40 ml) at room temperature for 20 hour. Acidification and extraction with methylene chloride yielded a product which was distilled to give 4-decanolide (5.5 g., 65% yield; b.p. 140°-145°/10 torr).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8](=[O:10])[CH3:9])[CH:5]=[CH:6][CH:7]=1.[NH:11]1[CH2:14][CH2:13][C:12]1=[O:15]>>[C:8]([C:4]1[CH:3]=[C:2]([N:11]2[CH2:14][CH2:13][C:12]2=[O:15])[CH:7]=[CH:6][CH:5]=1)(=[O:10])[CH3:9]
Reactant: CC(=O)c1cccc(Br)c1
Reactant: O=C1CCN1
Product: CC(=O)c1cccc(N2CCC2=O)c1
Yield: 97 %

Procedure:
The title compound was prepared in 97% yield according to the general procedure for the preparation of the amides, ureas and carbamates (Method A) starting from 1-(3-bromophenyl)ethanone and 2-azetidinone.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11](=O)[C:12]([F:18])([F:17])[C:13]([F:16])([F:15])[F:14])[CH:5]=[CH:6][C:7]=1[F:8].Cl.[F:21][C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[NH:29][NH2:30]>C(O)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]([CH:9]2[N:29]([C:23]3[CH:24]=[CH:25][C:26]([F:28])=[CH:27][C:22]=3[F:21])[N:30]=[C:11]([C:12]([F:18])([F:17])[C:13]([F:16])([F:15])[F:14])[CH2:10]2)[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: O=C(C=Cc1ccc(F)c(Br)c1)C(F)(F)C(F)(F)F
Reactant: NNc1ccc(F)cc1F
Agent: Cl
Solvent: CC(=O)O
Product: Fc1ccc(N2N=C(C(F)(F)C(F)(F)F)CC2c2ccc(F)c(Br)c2)c(F)c1
Temperature: 125 °C
Reaction time: 2 h
Yield: 62.5 %

Procedure:
1-(3-Bromo-4-fluoro-phenyl)-4,4,5,5,5-pentafluoro-pent-1-en-3-one (2.5 g, 7.1 mmol) prepared in Step 4 and 2,4-difluorophenylhydrazine hydrochloride (1.4 g, 7.8 mmol) were added to acetic acid (35.0 mL). The reaction mixture was stirred at 125° C. for 2 hours, concentrated under reduced pressure, and then ethyl acetate was added thereto. The mixture was washed with a saturated solution of sodium hydrogen carbonate, dried on anhydrous magnesium sulfate, and then concentrated under reduced pressure to give a yellow liquid residue. The resulting residue was purified by silica gel column chromatography (eluent: ethyl acetate/n-hexane=1/30) to give 2.1 g of the titled compound as a yellow liquid.
Reaction SMILES: [OH:1][C:2]1[CH:9](C(OC)=O)[CH:8]2[CH2:14][CH:4]([CH:5](C(OC)=O)[C:6]([OH:19])=[C:7]2C(OC)=O)[C:3]=1C(OC)=O.Cl.O.C(O)(=O)C>CC(C)=O>[CH:4]12[CH2:14][CH:8]([CH2:7][C:6](=[O:19])[CH2:5]1)[CH2:9][C:2](=[O:1])[CH2:3]2
Reactant: COC(=O)C1=C(O)C(C(=O)OC)C2CC1C(C(=O)OC)C(O)=C2C(=O)OC
Agent: Cl
Solvent: CC(C)=O
Solvent: CC(=O)O
Solvent: O
Product: O=C1CC2CC(=O)CC(C1)C2
Temperature: 130 °C
Yield: 85.4 %

Procedure:
A suspension of tetramethyl 3,7-dihydroxybicyclo[3.3.1]nona-2,6-diene-2,4,6,8-tetracarboxylate (19.2 g, 50 mmol) in an aqueous solution of 10 M HCl (50 mL), water (50 mL) and glacial acetic acid (100 mL) was heated at 130° C. for 6 h. After cooling at room temperature, the reaction mixture was poured onto crushed ice (200 mL) and extracted with DCM (4×200 mL). The combined organic layers were washed with an aqueous saturated solution of NaHCO3. The organic layer was dried over MgSO4, and concentrated under reduced pressure to give an orange solid. This crude product was dissolved in acetone and the salts which precipitated were filtered. Concentration of the filtrate and washing with Et2O afford the desired diketone (1) as a white solid (6.5 g, 85%).
Reaction SMILES: [Cl:1][CH2:2][CH:3]([C@H:5]([NH:13][C:14]([C@@H:16]([N:18]([CH3:27])[C:19](=[O:26])[CH2:20][CH2:21][CH2:22][CH2:23][CH:24]=[CH2:25])[CH3:17])=[O:15])[CH2:6][CH:7]([CH3:12])[CH2:8][CH2:9]C=C)[OH:4]>C(Cl)Cl.Cl[Ru](=C1N(C2C(C)=CC(C)=CC=2C)CCN1C1C(C)=CC(C)=CC=1C)(Cl)(=CC1C=CC=CC=1)[P](C1CCCCC1)(C1CCCCC1)C1CCCCC1>[Cl:1][CH2:2][CH:3]([CH:5]1[NH:13][C:14](=[O:15])[C@H:16]([CH3:17])[N:18]([CH3:27])[C:19](=[O:26])[CH2:20][CH2:21][CH2:22][CH2:23][CH:24]=[CH:25][CH2:9][CH2:8][C@@H:7]([CH3:12])[CH2:6]1)[OH:4]
Reactant: C=CCCCCC(=O)N(C)[C@@H](C)C(=O)N[C@H](CC(C)CCC=C)C(O)CCl
Agent: Cc1cc(C)c(N2CCN(c3c(C)cc(C)cc3C)C2=[Ru](Cl)(Cl)(=Cc2ccccc2)[P](C2CCCCC2)(C2CCCCC2)C2CCCCC2)c(C)c1
Agent: C[C@@H]1CC/C=C/CCCCC(=O)N(C)[C@@H](C)C(=O)NC(C(O)CCl)C1
Solvent: ClCCl
Product: C[C@@H]1CCC=CCCCCC(=O)N(C)[C@@H](C)C(=O)NC(C(O)CCl)C1

Procedure:
A solution of 1.38 g (3.44 mmol) hept-6-enoic acid {(S)-1-[(R)-1-(2-chloro-1-hydroxy-ethyl)-3-methyl-hept-6-enylcarbamoyl]-ethyl}-methyl-amide in 17 ml DCM is added dropwise within an hour to a refluxing solution of 146 mg [1,3-bis-(2,4,6-trimethylphenyl)-2-imidazolidinylidene)-dichloro(phenylmethylene)-(tricyclohexylphosphine)ruthenium](Grubbs II catalyst) in 340 ml DCM. The mixture is refluxed for an additional hour and the solvent evaporated. The residue is purified by chromatography on silica gel (DCM/methanol 95/5), giving the desired product as a brownish foam (mixture of diastereomers).
Reaction SMILES: [CH:1]1([C:7]([OH:9])=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[N+](=[CH2:12])=[N-]>CCOCC>[CH:1]1([C:7]([O:9][CH3:12])=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=C(O)C1CCCCC1
Reactant: C=[N+]=[N-]
Solvent: CCOCC
Product: COC(=O)C1CCCCC1
Temperature: 0 °C
Yield: 67.2 %

Procedure:
To an ice-cooled and stirred solution of cyclohexanecarboxylic acid (7.4 g, 0.058 mol) in 30 ml of ether was slowly added an excess solution of diazomethane in ether. After concentration of ether, the residue was distilled under reduced pressure to give a colorless transparent liquid of methyl cyclohexanecarboxylate (5.6 g, 0.039 mol, yield 67.2%, b.p. 73°-74° C./16 mmHg), which was assigned the structure by the following data:
Reaction SMILES: Cl.N1C=CC=C([CH:8]2[N:12]3[CH:13]=[CH:14][C:15]([C:16]([OH:18])=O)=[C:11]3[CH2:10][S:9]2)C=1.[NH2:19]C1C=C(C=CC=1Cl)C(C1C=CC=CC=1)=O.C>O1CCOCC1.C(#N)C.C(N(CC)CC)C>[CH2:10]1[S:9][CH2:8][N:12]2[CH:13]=[CH:14][C:15]([C:16]([NH2:19])=[O:18])=[C:11]12
Reactant: Nc1cc(C(=O)c2ccccc2)ccc1Cl
Reactant: O=C(O)c1ccn2c1CSC2c1cccnc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Solvent: CC#N
Product: NC(=O)c1ccn2c1CSC2
Temperature: 60 °C
Reaction time: 0.67 h
Yield: 124.3 %

Procedure:
Hydrochloride of the acid chloride derived from (+)-3-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole-7-carboxylic acid (5.4 g) is added, at a temperature between 60° and 62° C., to a solution of 3-amino-4-chlorobenzophenone (4.1 g) and triethylamine (3.65 g) in dioxane (80 cc) which is heated to a temperature in the vicinity of 60° C., in the course of 15 minutes. The suspension obtained is heated, with stirring, at a temperature in the vicinity of 100° C. for 5 hours and 40 minutes and then stirred at a temperature in the vicinity of 20° C. for 16 hours. The solvent is evaporated off under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the vicinity of 50° C. The residue is dissolved in methylene chloride (250 cc). The solution obtained is washed twice with distilled water (200 cc in total), with an aqueous 2N sodium hydroxide solution (100 cc) and then 3 times with distilled water (300 cc in total) and then dried over anhydrous magnesium sulphate, treated with decolourizing charcoal (0.5 g), filtered and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the vicinity of 45° C. A crude product (8.3 g) is thereby obtained, which is dissolved in boiling acetonitrile (50 cc). Decolourizing charcoal (0.5 g) is added to the solution obtained and the suspension is filtered in the heated state. The filtrate is cooled at a temperature in the vicinity of 4° C. for 1 hour. The crystals formed are separated by filtration, washed twice with acetonitrile cooled to a temperature in the vicinity of 4° C. (30 cc in total) and twice with diethyl ether (60 cc in total) and then dried under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature in the vicinity of 20° C. in the presence of potassium hydroxide pellets. (+)-N-(2-chloro-5-benzoylphenyl)-3- pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole-7-carboxamide (3.7 g) in the form of cream-coloured crystals, m.p. 154° C., is thereby obtained.