Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][S:2]([O:5]S(C)(=O)=O)(=O)=[O:3].[CH2:10]([O:12][CH2:13][C:14]1[N:15]([CH2:31][CH2:32][CH2:33][CH2:34][NH2:35])[C:16]2[CH:21]=[C:20]([CH3:22])[N:19]=[C:18]([O:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:17]=2[N:30]=1)[CH3:11]>C(Cl)(Cl)Cl.C(N(CC)CC)C>[CH2:10]([O:12][CH2:13][C:14]1[N:15]([CH2:31][CH2:32][CH2:33][CH2:34][NH:35][S:2]([CH3:1])(=[O:5])=[O:3])[C:16]2[CH:21]=[C:20]([CH3:22])[N:19]=[C:18]([O:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C:17]=2[N:30]=1)[CH3:11]
Reactant: CS(=O)(=O)OS(C)(=O)=O
Reactant: CCOCc1nc2c(Oc3ccccc3)nc(C)cc2n1CCCCN
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: CCOCc1nc2c(Oc3ccccc3)nc(C)cc2n1CCCCNS(C)(=O)=O
Reaction time: 2.5 h
Yield: 142.1 %

Procedure:
Methane sulfonic anhydride (0.822 g, 4.72 mmol) was added over a period of 5 minutes to a solution of 4-[2-(ethoxymethyl)-6-methyl-4-phenoxy-1H-imidazo[4,5-c]pyridin-1-yl]butan-1-amine (1.5 g, 4.23 mmol) in a mixture of chloroform (35 mL) and triethylamine (0.77 mL). The reaction mixture was allowed to stir for 2.5 hours then it was washed with 1N sodium hydroxide (10 mL), dried over magnesium sulfate and then concentrated under reduced pressure to provide 2.6 g of crude N-[4-(2-ethoxymethyl-6-methyl-4-phenoxy-1H-imidazo[4,5-c]pyridin-1-yl)butyl]methanesulfonamide.
Reaction SMILES: [CH:1]1[C:11]2[C:10]3[CH2:12][CH2:13][CH:14]=[CH:15][C:9]=3[CH:8]=[CH:7][C:6](=[CH:16][C:17]([NH:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25]([OH:27])=O)=[O:18])[C:5]=2[CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.ClC(OCC)=O.[NH2:41][OH:42]>[Cl-].[Na+].O.CN(C=O)C>[CH:1]1[C:11]2[C:10]3[CH2:12][CH2:13][CH:14]=[CH:15][C:9]=3[CH:8]=[CH:7][C:6](=[CH:16][C:17]([NH:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][C:25]([NH:41][OH:42])=[O:27])=[O:18])[C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: O=C(O)CCCCCNC(=O)C=C1C=CC2=C(CCC=C2)c2ccccc21
Reactant: NO
Agent: CCOC(=O)Cl
Agent: [Cl-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Solvent: CCN(CC)CC
Product: O=C(C=C1C=CC2=C(CCC=C2)c2ccccc21)NCCCCCC(=O)NO
Temperature: 0 °C
Reaction time: 2 h
Yield: 47 %

Procedure:
6-(2-(10,11-dihydro-5H-dibenzocyclohepten-5-ylidene)acetamido)hexanoic acid (363 mg, 1 mmol), triethylamine (151 mg, 1.5 mmol) and 20 ml of DMF were stirred at 0° C. while ethyl chloroformate (163 mg, 1.5 mmol) was added. The mixture was stirred at 0° C. for 2 hours, and then 50% aqueous solution of hydroxylamine (1.32 g, 20 mmol) was added. The mixture was stirred for 3 hours at room temperature, and then diluted with 1000 mL of brine. The solids were collected by vacuum filtration, washed with water and dried under vacuum to give the title compound (178 mg, 47%) as a yellow solid. LC-MS (m/z) 379 (M+1).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([Br:8])[C:5]([OH:9])=[CH:4][C:3]=1[N:10]1[C:14](=[O:15])[N:13]([CH:16]([F:18])[F:17])[C:12]([CH3:19])=[N:11]1.Br[CH:21]([CH3:27])[C:22]([O:24][CH2:25][CH3:26])=[O:23]>CN(C)C=O.C(OCC)C>[Br:8][C:6]1[CH:7]=[C:2]([Br:1])[C:3]([N:10]2[C:14](=[O:15])[N:13]([CH:16]([F:17])[F:18])[C:12]([CH3:19])=[N:11]2)=[CH:4][C:5]=1[O:9][CH:21]([CH3:27])[C:22]([O:24][CH2:25][CH3:26])=[O:23]
Reactant: Cc1nn(-c2cc(O)c(Br)cc2Br)c(=O)n1C(F)F
Reactant: CCOC(=O)C(C)Br
Solvent: CN(C)C=O
Solvent: CCOCC
Product: CCOC(=O)C(C)Oc1cc(-n2nc(C)n(C(F)F)c2=O)c(Br)cc1Br
Reaction time: 2 h
Yield: 64.6 %

Procedure:
To a stirred solution of 1.25 g (0.0031 mole) of 1-(2,4-dibromo-5-hydroxyphenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-one in 60 mL of N,N-dimethylformamide was added 0.57 g (0.0033 mole) of ethyl 2-bromopropionate. The resultant mixture was heated at 130° . for two hours, then was cooled. The solvent was evaporated from the mixture under reduced pressure, leaving a solid. This solid was dissolved in diethyl ether, and the solution was washed first with water, then with an aqueous 10% sodium hydroxide solution. The organic solution was dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure to yield 1.0 g of ethyl 2-[2,4-dibromo-5-(4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl)phenoxy]propionate as an oil, Compound 8.
Reaction SMILES: [CH2:1]([NH:8][CH2:9][CH:10]([OH:15])[C:11]([F:14])([F:13])[F:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[Br:23][CH:24]([CH3:28])[C:25](Cl)=[O:26]>C(Cl)Cl>[CH2:1]([N:8]([CH2:9][CH:10]([OH:15])[C:11]([F:14])([F:13])[F:12])[C:25](=[O:26])[CH:24]([Br:23])[CH3:28])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: OC(CNCc1ccccc1)C(F)(F)F
Reactant: CC(Br)C(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(Br)C(=O)N(Cc1ccccc1)CC(O)C(F)(F)F
Reaction time: 0.08 h

Procedure:
A solution of 3-(Benzylamino)-1,1,1-trifluoropropan-2-ol (2.68 g, 12.3 mmol) and triethylamine (1.7 mL, 12.2 mmol) in CH2Cl2 is cooled to 0° C. The solution is treated drop wise with 2-bromopropanoyl chloride (1.2 mL, 12 mmol, Aldrich) and stirred for 5 minutes. The solution is diluted to 100 mL with CH2Cl2 and washed sequentially with 1.0M HCl, saturated NaHCO3, and brine (100 mL each). The organic layer is dried over Na2SO4 and filtered. The solvent is removed by rotary evaporation yielding (N-benzyl-2-bromo-N-(3,3,3-trifluoro-2-hydroxypropyl)propanamide as a golden oil. Dry NaH is suspended in dry, inhibitor free THF (25 ml) in a flame dried flask and the mixture is cooled to 0° C. with stirring on an ice bath. The N-benzyl-2-bromo-N-(3,3,3-trifluoro-2-hydroxypropyl)propanamide (4.25 g, 12 mmol) is added as a solution in dry, inhibitor free THF (25 ml) and the resultant suspension is warmed to RT. After stirring for one hour the reaction is quenched with MeOH over an ice bath until no more gas evolved and the mixture is poured into 1.0M HCl (200 mL). The aqueous mixture is extracted into MTBE (200 mL) and the organic layer is washed with saturated NaHCO3 and brine (200 mL each). The organic layer is dried over Na2SO4 and filtered, and the solvent is removed by rotary evaporation yielding an amber oil.
Reaction SMILES: C1(C)C=CC=CC=1.[CH3:8][C:9]([C:12]1[CH:13]=[C:14]([C:23](=O)[CH3:24])[CH:15]=[C:16]([C:19]([CH3:22])([CH3:21])[CH3:20])[C:17]=1[OH:18])([CH3:11])[CH3:10].[CH3:26][N:27]([CH3:35])[N:28]1[C:32](=[O:33])[CH2:31][S:30][C:29]1=[S:34].C([O-])(=O)C.[NH4+]>C(O)(=O)C>[CH3:11][C:9]([C:12]1[CH:13]=[C:14]([CH2:23][CH:24]=[C:31]2[S:30][C:29](=[S:34])[N:28]([N:27]([CH3:35])[CH3:26])[C:32]2=[O:33])[CH:15]=[C:16]([C:19]([CH3:22])([CH3:21])[CH3:20])[C:17]=1[OH:18])([CH3:8])[CH3:10]
Reactant: CN(C)N1C(=O)CSC1=S
Reactant: CC(=O)c1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: CC(=O)O
Solvent: Cc1ccccc1
Product: CN(C)N1C(=O)C(=CCc2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)SC1=S

Procedure:
To 675 ml of toluene were added 20.9 g of 1-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]ethanone, 13.3 g of N-dimethylaminorhodanine 6.5 g of ammonium acetate and about 20 ml of acetic acid. The mixture was heated at reflux temperature and any aqueous layer generated was collected in a Dean-Stark trap. Over the following 52 hours an additional 39 g of ammonium acetate and about 100 ml of acetic acid were added in increments and a total of 89.2 ml of aqueous phase was drawn off. Following workup by conventional techniques, 17.1 g of the desired subtitled intermediate was recovered.
Reaction SMILES: C(N1C=CN=C1)(N1C=CN=C1)=O.[OH:13][C:14]1[C:19]([C:20]([OH:22])=O)=[CH:18][N:17]=[C:16]2[S:23][C:24]([I:26])=[CH:25][C:15]=12.[Cl:27][C:28]1[CH:35]=[CH:34][C:31]([CH2:32][NH2:33])=[CH:30][CH:29]=1.CC(O)=O>CN(C=O)C>[Cl:27][C:28]1[CH:35]=[CH:34][C:31]([CH2:32][NH:33][C:20]([C:19]2[C:14]([OH:13])=[C:15]3[CH:25]=[C:24]([I:26])[S:23][C:16]3=[N:17][CH:18]=2)=[O:22])=[CH:30][CH:29]=1
Reactant: O=C(O)c1cnc2sc(I)cc2c1O
Reactant: NCc1ccc(Cl)cc1
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: CC(=O)O
Solvent: CN(C)C=O
Product: O=C(NCc1ccc(Cl)cc1)c1cnc2sc(I)cc2c1O
Temperature: 60 °C
Reaction time: 18 h
Yield: 74 %

Procedure:
Mercuric oxide (7.10 g) and iodine (8.32 g) are added portion-wise to a solution of ethyl 4-hydroxythieno[2,3-b]pyridine-5-carboxylate (J. Heterocyclic Chem. 1977, 14, 807) (5.22 g) in CHCl3 (90 mL). The reaction is stirred at rt for 18 h. The reaction mixture is filtered, and the solid is washed with CHCl3 (400 mL). The organic layer is washed with H2O (200 mL), dried with MgSO4, filtered, and concentrated in vacuo. The resulting orange solid is purified by column chromatography (CH2Cl2:heptane, 1:1). Fractions homogeneous by TLC are combined and concentrated in vacuo to yield 2.95 g (36%) of ethyl 4-hydroxy-2-iodothieno[2,3-b]pyridine-5-carboxylate as a pale yellow solid. Ethyl 4-hydroxy-2-iodothieno[2,3-b]pyridine-5-carboxylate (2.64 g) is suspended in 10% NaOH (21 mL) and heated to reflux. The reaction is stirred at reflux for 1 h and then cooled to rt. The reaction mixture is poured into H2O (80 mL). Conc. HCl is added until a precipitate forms, and 2.272 g (94%) of 4-hydroxy-2-iodothieno[2,3-b]pyridine-5-carboxylic acid is isolated as a white solid. Carbonyldiimidazole (1.34 g) is added to a solution of 4-hydroxy-2-iodothieno[2,3-b]pyridine-5-carboxylic acid (2.041 g) in DMF (58 mL). The reaction is heated to 60° C. and stirred for 18 h. The reaction mixture is cooled to rt, and 4-chlorobenzylamine (1.01 mL, 8.27) is added. The reaction is stirred at rt for 7 h. The reaction mixture is poured into 20% aqueous HOAc (180 mL), and the resulting white solid is filtered off. This material is recrystallized from methanol then toluene to yield 2.095 g (74%) of the title compound as a white solid.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]([CH:6]=O)=[CH:2]1.[Br-].[C:9]([CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)([OH:11])=[O:10]>>[S:1]1[CH:5]=[CH:4][C:3]([CH:6]=[CH:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][C:9]([OH:11])=[O:10])=[CH:2]1
Reactant: O=C(O)CCCCCCCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: O=Cc1ccsc1
Agent: [Br-]
Product: O=C(O)CCCCCCCC=Cc1ccsc1

Procedure:
Reaction of 3-thiophenecarboxaldehyde with (8-carboxy-octyl)-triphenyl-phosphonium bromide, in analogy with intermediate 22, step 2, produced 10-(thiophen-3-yl)-dec-9-enoic acid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:6][OH:7].[CH3:19][S:20](Cl)(=[O:22])=[O:21].CCN(CC)CC>C(Cl)Cl>[CH3:19][S:20]([O:7][CH2:6][C:5]1[CH:8]=[CH:9][C:10]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[C:3]([O:2][CH3:1])[CH:4]=1)(=[O:22])=[O:21]
Reactant: COc1cc(CO)ccc1OCc1ccccc1
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1cc(COS(C)(=O)=O)ccc1OCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of 3-(methoxy)-4-(benzyloxy)benzyl alcohol (0.244 g, 1.00 mmol) in CH2Cl2 (2.0 mL) was treated with methanesulfonylchloride (0.085 mL, 1.10 mmol) and Et3N (0.160 mL, 1.15 mmol). After stirring 1 h at ambient temperature, the reaction mixture was filtered through a short plug of silica gel using CH2Cl2 as the eluant. The solution was concentrated in vacuo and taken on without purification. MS (ES+) m/e 323 [M+H]+.
Reaction SMILES: [CH:1](Cl)([O:6][CH:7]([F:9])[F:8])[C:2]([F:5])([F:4])[F:3].[F-:11].[K+]>>[CH:7]([O:6][CH:1]([C:2]([F:5])([F:4])[F:3])[F:11])([F:9])[F:8]
Reactant: [F-]
Reactant: FC(F)OC(Cl)C(F)(F)F
Agent: [K+]
Product: FC(F)OC(F)C(F)(F)F
Temperature: 278 °C
Reaction time: 18 h
Yield: 13.3 %

Procedure:
A 1 liter autoclave (316SS, Parr) was charged with 171 g (0.93 moles) isoflurane and 116 g (2.0 moles) potassium fluoride. The reaction mass was heated with stirring to 278° C. After 18 hours at 278° C., the pressure was 500 psi. The autoclave was then cooled to room temperature for transfer to the laboratory. Products were then distilled into a dry ice cooled trap by heating the autoclave on a hot plate. The trap contents (134 g) were distilled through a four foot vacuum jacketed column packed with glass beads to give 20.8 g CHF2OCHFCF3 (bp 23.5° C.). The material remaining in the distillation flask (104.0 g) was 98% isoflurane. Based on the materials isolated, the percent conversion was 13% (33% yield). Details of the distillation are given below.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[C:6]#[N:7].[CH3:11][O:12][C:13]1[CH:34]=[CH:33][C:16]([C:17](Cl)([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)=[CH:15][CH:14]=1.O>CN(C=O)C.N1C=CC=CC=1>[CH3:25][O:24][C:21]1[CH:20]=[CH:19][C:18]([C:17]([O:1][CH2:2][C:3]2[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=2)[C:6]#[N:7])([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:16]2[CH:33]=[CH:34][C:13]([O:12][CH3:11])=[CH:14][CH:15]=2)=[CH:23][CH:22]=1
Reactant: COc1ccc(C(Cl)(c2ccccc2)c2ccc(OC)cc2)cc1
Reactant: N#Cc1cccc(CO)c1
Solvent: O
Solvent: CN(C)C=O
Solvent: c1ccncc1
Product: COc1ccc(C(OCc2cccc(C#N)c2)(c2ccccc2)c2ccc(OC)cc2)cc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 0.1 %

Procedure:
In DMF (23 mL) and pyridine (23 mL), suspended were 3-hydroxymethylbenzonitrile (1.12 g, 8.38 mmol) and 4,4′-dimethoxytritylchloride (3.41 g, 10.06 mmol). The suspension was stirred for 12 hours at a room temperature under Ar atmosphere. TLC was used to confirm there was no starting material in the reaction mixture. Then, to the suspension was added iced water (20 mL). The mixture was subjected to extraction with EtOAc and water. The organic layer was washed with sat. NaCl aq., dried over anhydrous Na2SO4, and evaporated under reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography (Hex:EtOAc=10:1) to give 3-(4,4′-dimethoxytrityloxymethyl)benzonitrile (4) (3.31 mg, 91%) as a colorless oil.
Reaction SMILES: [F:1][CH2:2][C:3]([N:11]1[C:15](=[O:16])[C:14]2=[CH:17][CH:18]=[CH:19][CH:20]=[C:13]2[C:12]1=[O:21])([CH2:6][CH2:7][CH2:8][CH2:9][OH:10])[C:4]#[N:5].N1C=CC=CC=1.[CH3:28][S:29](Cl)(=[O:31])=[O:30]>ClCCl>[F:1][CH2:2][C:3]([N:11]1[C:12](=[O:21])[C:13]2=[CH:20][CH:19]=[CH:18][CH:17]=[C:14]2[C:15]1=[O:16])([CH2:6][CH2:7][CH2:8][CH2:9][O:10][S:29]([CH3:28])(=[O:31])=[O:30])[C:4]#[N:5]
Reactant: N#CC(CF)(CCCCO)N1C(=O)c2ccccc2C1=O
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: CS(=O)(=O)OCCCCC(C#N)(CF)N1C(=O)c2ccccc2C1=O
Reaction time: 8 h
Yield: 94.9 %

Procedure:
A solution of 2-fluoromethyl-2-phthalimido-6-hydroxy-hexanenitrile (9.0 g, 31 mmol) and pyridine (60 ml) in dry dichloromethane (150 ml) is cooled in an ice bath, and methanesulfonyl chloride (3.6 g, 31 mmol), diluted with a small amount of dichloromethane, is added slowly with efficient stirring. Stirring is continued at room temperature overnight. The reaction mixture is washed with 2 N HCl and dried. Evaporation of solvent gives the title compound as a yellow oil (10.84 g).
Reaction SMILES: C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[CH3:15][C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([C:25]3[O:29][C:28]([NH2:30])=[N:27][CH:26]=3)[CH:23]=2)[NH:18][N:17]=1.[C:31]([O:35][C:36]([NH:38][C@@H:39]([CH2:43][C:44]1[CH:49]=[CH:48][C:47]([C:50]([F:53])([F:52])[F:51])=[CH:46][CH:45]=1)[C:40](O)=[O:41])=[O:37])([CH3:34])([CH3:33])[CH3:32]>>[CH3:15][C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([C:25]3[O:29][C:28]([NH:30][C:40](=[O:41])[C@@H:39]([NH:38][C:36](=[O:37])[O:35][C:31]([CH3:32])([CH3:33])[CH3:34])[CH2:43][C:44]4[CH:45]=[CH:46][C:47]([C:50]([F:53])([F:52])[F:51])=[CH:48][CH:49]=4)=[N:27][CH:26]=3)[CH:23]=2)[NH:18][N:17]=1
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccc(C(F)(F)F)cc1)C(=O)O
Reactant: Cc1n[nH]c2ccc(-c3cnc(N)o3)cc12
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Product: Cc1n[nH]c2ccc(-c3cnc(NC(=O)[C@H](Cc4ccc(C(F)(F)F)cc4)NC(=O)OC(C)(C)C)o3)cc12

Procedure:
This intermediate was prepared by EDC-HOBt coupling of 5-(3-methyl-1H-indazol-5-yl)oxazol-2-amine with (S)-2-(tert-butoxycarbonylamino)-3-(4-(trifluoromethyl)phenyl)propanoic acid (purchased from Peptech (CAS No. 114873-07-3)) using a standard procedure such as described in Bioorg. Med. Chem. 14(2), 418-425; 2006) which is hereby incorporated by reference in its entirety as if specifically set forth herein.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[CH:11][N:10]([C:13]3[C:18]([Cl:19])=[CH:17][C:16]([N+:20]([O-])=O)=[CH:15][C:14]=3[Cl:23])[N:9]=2)=[CH:4][CH:3]=1>C1COCC1.C(O)C.[Pt](=O)=O>[Cl:23][C:14]1[CH:15]=[C:16]([CH:17]=[C:18]([Cl:19])[C:13]=1[N:10]1[CH:11]=[CH:12][C:8]([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)=[N:9]1)[NH2:20]
Reactant: O=[N+]([O-])c1cc(Cl)c(-n2ccc(-c3ccc(Cl)cc3)n2)c(Cl)c1
Agent: O=[Pt]=O
Solvent: C1CCOC1
Solvent: CCO
Product: Nc1cc(Cl)c(-n2ccc(-c3ccc(Cl)cc3)n2)c(Cl)c1
Reaction time: 2 h

Procedure:
A solution of 3-(4-chlorophenyl)-1-(2,6-dichloro-4-nitrophenyl)-pyrazole (0.69 g, 1.87 mmol), prepared following the procedure of Example 9, in THF/ethanol (1:4; 35 ml) is treated with platinum dioxide (43 mg) and stirred under H2 at atmospheric pressure for 2 hours. The reaction mixture is filtered and concentrated to give 3,5-dichloro-4-[3-(4-chlorophenyl)-1-pyrazolyl]aniline.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[S:12][C:11]3[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=3[CH2:9][CH:8]([N:17]3[CH2:22][CH2:21][N:20]([CH2:23][CH2:24][CH2:25][OH:26])[CH2:19][CH2:18]3)[C:7]=2[CH:27]=1.[C:28](O)(=[O:36])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH3:35].O.[OH-].[NH4+]>C1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[S:12][C:11]3[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=3[CH2:9][CH:8]([N:17]3[CH2:18][CH2:19][N:20]([CH2:23][CH2:24][CH2:25][O:26][C:28](=[O:36])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH3:35])[CH2:21][CH2:22]3)[C:7]=2[CH:27]=1
Reactant: COc1ccc2c(c1)C(N1CCN(CCCO)CC1)Cc1ccccc1S2
Reactant: CCCCCCCC(=O)O
Agent: [NH4+]
Agent: [OH-]
Solvent: c1ccccc1
Solvent: O
Product: CCCCCCCC(=O)OCCCN1CCN(C2Cc3ccccc3Sc3ccc(OC)cc32)CC1
Temperature: 60 °C
Reaction time: 8 h

Procedure:
To a solution of 14.82 grams of 8-methoxy-10-[4-(3-hydroxypropyl)piperazino]-10,11-dihydrodibenzo[b,f]thiepin in 50 milliliters of benzene was added 12.55 grams of caprylic acid (octanoic acid). The resulting reaction mixture was allowed to stand overnight and was then heated for 3 hours at a temperature of 60°C. After cooling, the mixture was shaken with 100 milliliters of water, 20 milliliters of concentrated aqueous ammonium hydroxide solution was then added thereto, and the mixture was extracted with a mixture of benzene and ethyl ether. The resulting extract was washed with water, dried over anhydrous potassium carbonate, and the solvent was evaporated therefrom. The residue was dissolved in 40 milliliters of acetone and added to a solution of 9.5 grams of maleic acid in 30 milliliters of acetone. On standing, 15.5 grams of crude 8-methoxy-10-]4-(3-octanoyloxypropyl)piperazino]-10,11-dihydrobenzo[b,f]thiepin di(hydrogen maleate) crystals separated therefrom. On purification by recrystallization from acetone, the di(hydrogen maleate) salt had a melting point of 130°C. The free base was recovered in the form of a viscous oil by adding the di(hydrogen maleate) to a dilute aqueous ammonium hydroxide solution and extracting the solution with benzene as described in Example 1 hereinbefore.
Reaction SMILES: [H-].[Na+].[CH2:3]([OH:10])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[Br:11][C:12]1[C:13](F)=[C:14]([CH:17]=[CH:18][CH:19]=1)[C:15]#[N:16]>CN(C=O)C>[CH2:3]([O:10][C:13]1[C:12]([Br:11])=[CH:19][CH:18]=[CH:17][C:14]=1[C:15]#[N:16])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: OCc1ccccc1
Reactant: N#Cc1cccc(Br)c1F
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: N#Cc1cccc(Br)c1OCc1ccccc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 71.5 %

Procedure:
To a flask containing sodium hydride (1.44 g, 60.0 mmol) suspended in DMF (60 mL, 800 mmol) at 0° C. was added benzyl alcohol (6.21 mL, 60.0 mmol) over 5 min. The reaction mixture was stirred at 0° C. for 30 min and then 3-bromo-2-fluorobenzonitrile (10.0 g, 50.0 mmol) in DMF (20 mL) was added. The reaction mixture was warmed to room temperature and stirred at 80° C. for 2 h, cooled to room temperature, and extracted with ethyl acetate (150 mL) and water (150 mL) The organic layer was washed with water (150 mL) and brine (150 mL), collected, dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was suspended with ethyl acetate:hexanes (1:3; 50 mL). The resulting suspension was stirred vigorously for 1 h, filtered, and dried. The mother liquor was concentrated and recrystallized. The crystals were combined and dried under vacuum to give the title compound (10.3 g).
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[O:3][C:4]1[CH:9]=[CH:8][C:7](I)=[CH:6][CH:5]=1.C([Li])CCC.[CH:18](=[O:20])[CH3:19].[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1>C(OCC)C.CCCCCC.C(Cl)Cl.O.C(O)(=O)C>[CH3:19][C:18]([C:7]1[CH:8]=[CH:9][C:4]([O:3][C:2]([F:12])([F:11])[F:1])=[CH:5][CH:6]=1)=[O:20]
Reactant: CC=O
Reactant: FC(F)(F)Oc1ccc(I)cc1
Agent: O=[Cr](=O)([O-])Cl
Agent: [Li]CCCC
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Solvent: CCOCC
Solvent: CCCCCC
Product: CC(=O)c1ccc(OC(F)(F)F)cc1
Reaction time: 0.33 h

Procedure:
A solution of 4-(trifluoromethoxy)iodobenzene (8.64 g.) in anhydrous diethyl ether (60 ml.) was added dropwise at -65° C. to n-butyl-lithium (21 ml. of a 1.6M solution in hexane) over 20 minutes. After stirring for a further 20 minutes, a solution of acetaldehyde (1.6 g.) in diethyl ether (15 ml.) was added, keeping the temperature below -60° C. Stirring was continued for 1 hour, after which time the temperature was allowed to rise to -30° C. and a mixture of glacial acetic acid (15 ml) and diethyl ether (20 ml.) was added. On reaching room temperature, the solution was poured into water, the organic layer was separated, washed with water and then sodium bicarbonate solution, dried over sodium sulphate and filtered, and the solvents were evaporated to give a pale yellow oil which was purified by column chromatography on silica and using chloroform, then chloroform/ethyl acetate (7:3 v/v) as eluent. Evaporation of the appropriate fractions gave a colourless oil which was dissolved in methylene dichloride (60 ml.) and treated with pyridinium chlorochromate (7.35 g.). After stirring for 3 hours, the reaction mixture was diluted with diethyl ether (100 ml.), and the suspension was filtered through a "Florosil" (trade mark) silica pad. Evaporation of the solvent gave 4-trifluoromethoxyacetophenone as a pale yellow oil. N.m.r. in deuteriochloroform gave signals at 2.59 (3H, singlet) and 7.7 (4H, quartet).
Reaction SMILES: [C:1]([O:10][CH2:11][CH:12]([OH:24])[CH2:13][O:14][C:15](=[O:23])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])(=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].C(N(CC)CC)C.[C:32]1(=[O:39])[O:38][C:36](=[O:37])[CH2:35][CH2:34][CH2:33]1.C([O-])(=O)CCCCCCC>CCOCC.C(Cl)Cl>[C:32]([O:24][CH:12]([CH2:13][O:14][C:15](=[O:23])[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[CH2:11][O:10][C:1](=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])(=[O:39])[CH2:33][CH2:34][CH2:35][C:36]([OH:38])=[O:37]
Reactant: CCCCCCCC(=O)OCC(O)COC(=O)CCCCCCC
Reactant: O=C1CCCC(=O)O1
Agent: CCCCCCCC(=O)[O-]
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CCOCC
Product: CCCCCCCC(=O)OCC(COC(=O)CCCCCCC)OC(=O)CCCC(=O)O

Procedure:
A solution of 2-hydroxy-3-octanoyloxypropyl octanoate (5.0 g.) in ether (30 ml.) was stirred with triethylamine (2.04 ml.) and glutaric anhydride (1.66 g.) for 3.5 hours. Further glutaric anhydride (0.8 g.) was then added together with triethylamine (1.0 ml.). This mixture was heated under reflux until no further starting octanoate could be detected by thin layer chromatography (silica: methylene chloride). The cooled reaction mixture was washed with 1M hydrochloric acid (2×20 ml.), then with water (2×20 ml.), dried (MgSO4) and evaporated to give 2-octanoyloxy-1-(octanoyloxymethyl)ethyl hydrogen glutarate as an oil (6.62 g.); NMR (CDCl3): 0.9 (6H, t, CH3), 1.1-2.1 (22H, m, CH2), 2.4 (8H, m, CH2CO), 4.0-4.4 (4H,m, CH2O), 5.1-5.4 (1H, br.t, CHO), 9.6 (1H, br.s, CO2H)ppm. Mass spectrum (major diagnostic peaks based on M=458, using chemical ionisation techniques): m/e 476 (M+NH4), 360 (M +NH4 --HO2C.(CH2)3.CO2H)