Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([N:11]([CH3:13])[CH3:12])(=[O:10])=[O:9].C([Li])CCC.[S:19](Cl)([Cl:22])(=[O:21])=[O:20]>CCOCC>[Cl:1][C:2]1[C:3]([S:8](=[O:9])(=[O:10])[N:11]([CH3:13])[CH3:12])=[C:4]([S:19]([Cl:22])(=[O:21])=[O:20])[CH:5]=[CH:6][CH:7]=1
Reactant: O=S(=O)(Cl)Cl
Reactant: CN(C)S(=O)(=O)c1ccccc1Cl
Agent: [Li]CCCC
Solvent: CCOCC
Product: CN(C)S(=O)(=O)c1c(Cl)cccc1S(=O)(=O)Cl
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a stirred mixture of 29 g of 2-chloro-N,N-dimethylbenzenesulfonamide and 150 mL ether at -5° C. to 0° C. was added dropwise under nitrogen 94 mL of a 1.55M solution of n-butyllithium in hexanes. When the addition was complete, the reaction mixture was allowed to warm to room temperature and was stirred for 2 hours. The reaction mixture was then recooled to -30° C. to -20° C., and treated with a solution of 22 mL of sulfuryl chloride in 60 mL hexanes, added at a rate that maintained the temperature below -10° C. The reaction mixture was then stirred at room temperature for one hour. The precipitated solids were collected, washed with ether and water, and dried to afford 26 g of 3-chloro-2-(N,N-dimethylsulfamoyl)benzenesulfonyl chloride as a yellow solid, which was used without further purification; IR (KBr): 1375, 1350, 1180 and 1160 cm-1.
Reaction SMILES: [C:1]1([N:11]=[C:12]=[O:13])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[NH:14]1[CH2:19][CH2:18][CH:17]([CH2:20][CH2:21][CH2:22][CH2:23][NH:24][C:25](=[O:34])[CH:26]=[CH:27][C:28]2[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=2)[CH2:16][CH2:15]1>C1COCC1>[C:1]1([NH:11][C:12]([N:14]2[CH2:19][CH2:18][CH:17]([CH2:20][CH2:21][CH2:22][CH2:23][NH:24][C:25](=[O:34])[CH:26]=[CH:27][C:28]3[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=3)[CH2:16][CH2:15]2)=[O:13])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: O=C(C=Cc1cccnc1)NCCCCC1CCNCC1
Reactant: O=C=Nc1cccc2ccccc12
Solvent: C1CCOC1
Product: O=C(C=Cc1cccnc1)NCCCCC1CCN(C(=O)Nc2cccc3ccccc23)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
2.35 g (13.9 mmol) 1-naphthyl isocyanate are dissolved in 10 ml abs. THF and a solution of 4.0 g (13.9 mmol) N-[4-(piperidin-4-yl)-butyl]-3-(pyridin-3-yl)-acrylamide (substance 14) in 30 ml abs. THF is added dropwise at RT under moisture exclusion. After ca one hour, a white precipitate forms and the suspension is stirred at RT overnight. The solid is drawn off, chromatographically purified over silica gel with CHCl3/CH3OH (95/5 to 93/7) and crystallized from isopropanol after removal of the solvent. Colorless crystals remain with a MP of 198–200° C.; yield: 2.2 g (34%).
Reaction SMILES: [N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:21]=[CH:20][C:9]2[C:10]([O:13][CH:14]([CH3:19])[C:15]([O:17][CH3:18])=[O:16])=[N:11][O:12][C:8]=2[CH:7]=1>S(=O)(=O)(O)O.CCOCC.C(Cl)Cl>[Cl:5][C:6]1[C:21]([N+:1]([O-:4])=[O:2])=[CH:20][C:9]2[C:10]([O:13][CH:14]([CH3:19])[C:15]([O:17][CH3:18])=[O:16])=[N:11][O:12][C:8]=2[CH:7]=1
Reactant: O=[N+]([O-])O
Reactant: COC(=O)C(C)Oc1noc2cc(Cl)ccc12
Agent: O=S(=O)(O)O
Solvent: ClCCl
Solvent: CCOCC
Product: COC(=O)C(C)Oc1noc2cc(Cl)c([N+](=O)[O-])cc12
Reaction time: 1 h

Procedure:
Nitric acid (70%, 3.0 mL, 47 mmol) is slowly added to a mixture of methyl 2-[(6-chloro-1,2-benzisoxazol-3-yl)oxy]propionate (6.0 g, 23.5 mmol) in concentrated sulfuric acid (50 mL) while maintaining the temperature below 10° C. The reaction mixture is stirred for 1 hour on an ice/water bath and poured onto ice. The resultant aqueous mixture is diluted with ether, stirred for several minutes and the ether is allowed to evaporate overnight. The resultant mixture is filtered to obtain a solid which is dissolved in methylene chloride. The methylene chloride solution is dried over anhydrous sodium sulfate and concentrated in vacuo to obtain a solid which is recrystallized from an ether/hexanes solution to give the title product as a solid, mp 98°-101° C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([NH:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=2[N+]([O-])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:25][O:26][C:27](=[O:30])[CH2:28]Br.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O.C(OCC)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([N:13]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)[CH2:28][C:27]([O:26][CH3:25])=[O:30])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: COC(=O)CBr
Reactant: CC(C)(C)OC(=O)N1CCC(NCc2ccc(Cl)cc2[N+](=O)[O-])C1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOCC
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)CN(Cc1ccc(Cl)cc1)C1CCN(C(=O)OC(C)(C)C)C1

Procedure:
To a solution of 3-(4-Chloro-2-nitro-benzylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester (3.8 g, 10.7 mmol) in DMF (40 mL) was added Bromo-acetic acid methyl ester (1.01 mL, 10.7 mmol) and K2CO3 (1.48 g, 10.7 mmol). The resultant suspension was stirred at 70° C. overnight. The reaction mixture was diluted with water and ethyl ether. The organic extract was dried over MgSO4, filtered and concentrated to provide the desired product as an oil. The crude product was purified on SiO2 and concentrated to provide the desired product as an oil (2 g, 44%). LCMS (retention time=3.03, ES+428).
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][S:6][C@H:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:4]([CH2:14][C:15]([O:17][CH2:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])=[O:16])[C:3]1=[O:24].C(=O)(O)[O-].[Na+].[CH2:30]([O:32][C:33](=[O:44])[C:34](=O)[CH2:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[CH3:31].C([BH3-])#N.[Na+]>C(O)(C)C>[CH2:30]([O:32][C:33]([CH:34]([NH:1][CH:2]1[CH2:7][S:6][C@H:5]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:4]([CH2:14][C:15]([O:17][CH2:18][CH2:19][Si:20]([CH3:21])([CH3:23])[CH3:22])=[O:16])[C:3]1=[O:24])[CH2:35][CH2:36][C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1)=[O:44])[CH3:31]
Reactant: CCOC(=O)C(=O)CCc1ccccc1
Reactant: C[Si](C)(C)CCOC(=O)CN1C(=O)C(N)CS[C@@H]1c1ccccc1
Agent: O=C([O-])O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(C)O
Product: CCOC(=O)C(CCc1ccccc1)NC1CS[C@H](c2ccccc2)N(CC(=O)OCC[Si](C)(C)C)C1=O
Reaction time: 1 h

Procedure:
A solution of (R)-dihydro-5-amino-4-oxo-2-phenyl-2H-1,3-thiazine-3(4H)-acetic acid, 2-(trimethylsilyl)ethyl ester (9 mmole) in dry isopropanol (12 ml.) under nitrogen is treated with sodium bicarbonate (2.25 mmole) followed by ethyl-2-oxo-4-phenylbutyrate (9.3 g., 45 mmole) dissolved in isopropanol (8 ml.). To the resulting suspension is added powdered 3 A° molecular sieves (8 g.). The reaction mixture is stirred for one hour while the pH is maintained at around 7.0. Next a solution of sodium cyanoborohydride (1.13 g., 18 mmole) in isopropanol (14 ml.) is added incrementally over a 5 hour period while continuing to maintain neutral pH. The reaction mixture is then stirred overnight at room temperature, then filtered (celite), concentrated in vacuo, and partitioned between ether and water. Normal work up of the organic extract followed by column chromatography on silica gel yields (R)-dihydro-5-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]-4-oxo-2-phenyl-2H-1,3-thiazine-3(4H)-acetic acid, 2-(trimethylsilyl)ethyl ester as a mixture of diastereomers.
Reaction SMILES: [Cl:1][C:2]1[C:9]([Cl:10])=[C:8]([OH:11])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[C:12](=O)([O-])[O-].[K+].[K+].S(OC)(OC)(=O)=O.O>CN(C)C=O>[Cl:1][C:2]1[C:9]([Cl:10])=[C:8]([O:11][CH3:12])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5]
Reactant: O=Cc1ccc(O)c(Cl)c1Cl
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: COS(=O)(=O)OC
Solvent: CN(C)C=O
Solvent: O
Product: COc1ccc(C=O)c(Cl)c1Cl

Procedure:
A mixture of 2,3-dichloro-4-hydroxybenzaldehyde (19.1 gm., ;b 0.1 mole) and potassium carbonate (34.4 gm., 0.25 mole) in dimethylformamide (50 ml.) is stirred and treated dropwise over 15 minutes with dimethyl sulfate (14.1 gm., 0.11 mole). The reaction is exothermic; after 45 minutes the mixture is poured with stirring into water (300 ml.). The solid product that separates is removed by filtration, washed with water and then washed with a little methanol. After drying the yield of 2,3-dichloro-4-methoxybenzaldehyde is 16 gm., m.p., 117°-118° C.
Reaction SMILES: [CH2:1](Cl)[CH:2]=[C:3]([CH3:5])[CH3:4].[CH3:7][C:8]([CH3:10])=[O:9]>>[CH3:4][C:3]([CH3:5])=[CH:2][CH2:1][CH2:7][C:8](=[O:9])[CH3:10]
Reactant: CC(C)=O
Reactant: CC(C)=CCCl
Product: CC(=O)CCC=C(C)C

Procedure:
Process (iii): A process in which prenyl chloride obtained by the reaction of isoprene with hydrogen chloride is allowed to react with acetone in the presence of an equimolar amount of an alkali based on the prenyl chloride to give 6-methyl-5-hepten-2-one (see, e.g., U.S. Pat. Nos. 3,983,175 and 3,984,475).
Reaction SMILES: CS(O[CH2:6][C@@H:7]1[C@H:10]([NH:11][C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])[C:9](=[O:22])[N:8]1[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][C:25]=1[O:32][CH3:33])(=O)=O.[CH3:34][C:35]1[N:39]=[CH:38][NH:37][N:36]=1.C([O-])([O-])=O.[K+].[K+].[Na+].[I-]>CN(C=O)C>[CH3:33][O:32][C:25]1[CH:26]=[C:27]([O:30][CH3:31])[CH:28]=[CH:29][C:24]=1[CH2:23][N:8]1[C:9](=[O:22])[C@@H:10]([NH:11][C:12](=[O:13])[O:14][CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[C@H:7]1[CH2:6][N:36]1[C:35]([CH3:34])=[N:39][CH:38]=[N:37]1
Reactant: Cc1nc[nH]n1
Reactant: COc1ccc(CN2C(=O)[C@@H](NC(=O)OCc3ccccc3)[C@H]2COS(C)(=O)=O)c(OC)c1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1ccc(CN2C(=O)[C@@H](NC(=O)OCc3ccccc3)[C@H]2Cn2ncnc2C)c(OC)c1
Temperature: 70 °C
Yield: 44 %

Procedure:
((2S,3S)-3-(((benzyloxy)carbonyl)amino)-1-(2,4-dimethoxybenzyl)-4-oxoazetidin-2-yl)methyl methanesulfonate (3.74 g, 8.0 mmol), 3-methyl-1H-1,2,4-triazole (2.00 g, 24.0 mmol), K2CO3 (6.64 g, 48.0 mmol) and NaI (2.88 g, 17.2 mmol) were slurried in DMF (16 mL) and heated to 70° C. with stirring. After 24 h the mixture was concentrated in vacuo. The crude residue was purified via silica gel chromatography (MeOH-DCM, 2%) to afford title compounds (1.64 g, 44% combined) as an off-white solid (inseparable mixture). LCMS: m/z=466.2 (M+1).
Reaction SMILES: [CH3:1][C:2]([CH3:9])([CH3:8])[C:3](=O)[CH2:4][C:5]#[N:6].[NH:10]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=1)[NH2:11]>>[C:2]([C:3]1[CH:4]=[C:5]([NH2:6])[N:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)[N:11]=1)([CH3:9])([CH3:8])[CH3:1]
Reactant: CC(C)(C)C(=O)CC#N
Reactant: NNc1ccccn1
Product: CC(C)(C)c1cc(N)n(-c2ccccn2)n1
Yield: 99 %

Procedure:
The title compound was prepared from 4,4-dimethyl-3-oxopentane nitrile and 2-hydrazinopyridine, using the same method as that described for preparation 7, as a solid in 99% yield.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[CH3:11][C:12]1[NH:13][CH:14]=[CH:15][N:16]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[CH3:11][C:12]1[N:13]([C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=2)[CH:14]=[CH:15][N:16]=1
Reactant: Cc1ncc[nH]1
Reactant: O=[N+]([O-])c1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: Cc1nccn1-c1ccc([N+](=O)[O-])cc1
Temperature: 100 °C
Yield: 88.8 %

Procedure:
A mixture of 1-fluoro-4-nitrobenzene (10 g, 70.9 mmol), 2-methyl-1H-imidazole (5.8 g, 70.9 mmol), and Cs2CO3 (34.7 g, 106.4 mmol) in degassed DMF (200 mL) was heated at 100° C. under nitrogen overnight. When TLC indicated that 1-fluoro-4-nitrobenzene was consumed, the reaction mixture was concentrated in vacuo. The residue was diluted with water (300 mL), and a grey precipitate was formed and was isolated to give 2-methyl-1-(4-nitrophenyl)-1H-imidazole (12.8 g, yield 89%).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][C:16]([C:19]2([OH:23])[CH2:22][CH2:21][CH2:20]2)=[CH:15][C:14]=1[F:24].Cl([O-])=[O:26].[Na+].O.OP([O-])(O)=O.[Na+].CC(=CC)C>C(#N)C.C(O)(C)(C)C.O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:26])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][C:16]([C:19]2([OH:23])[CH2:22][CH2:21][CH2:20]2)=[CH:15][C:14]=1[F:24]
Reactant: [O-][Cl+][O-]
Reactant: O=Cc1c[nH]c2cc(Cl)c(-c3ccc(C4(O)CCC4)cc3F)cc12
Agent: CC=C(C)C
Agent: O=P([O-])(O)O
Agent: [Na+]
Solvent: O
Solvent: CC(C)(C)O
Solvent: CC#N
Product: O=C(O)c1c[nH]c2cc(Cl)c(-c3ccc(C4(O)CCC4)cc3F)cc12
Temperature: 25 °C
Reaction time: 24 h
Yield: 19.6 %

Procedure:
To a solution of 6-chloro-5-[2-fluoro-4-(1-hydroxycyclobutyl)phenyl]-1H-indole-3-carbaldehyde (57 mg, 0.17 mmol) in acetonitrile (1 mL) and tert-butanol (1 mL) was added a solution of sodium chlorite (112 mg, 1.7 mmol), sodium phosphate monobasic hydrate (199 mg, 1.7 mmol) in water (2 mL) and 2-methyl-2-butene (0.72 mL, 6.8 mmol). The mixture was stirred at room temperature for 24 hours. The mixture was concentrated in vacuo and treated with ethanol. The solids were filtered and the filtrate was concentrated in vacuo to give crude product, which was purified using reverse phase chromatography to give the title compound (12 mg, 20%). MS (ES+) 360.057 (M+H)+. Retention time: 2.60 min. Column: Waters Atlantis dC18 4.6×50 mm, 5 μm. Modifier: TFA 0.05%. Gradient: 95% H2O/5% MeCN linear to 5% H2O/95% MeCN over 4.0 min, HOLD at 5% H2O/95% MeCN to 5.0 min. Flow: 2.0 mL/min.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:14][CH2:13][CH2:12][C@H:11]2[CH2:15][N:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[O:9])=[C:4]([F:21])[CH:3]=1.[CH3:22][S:23]([C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1)=[O:24]>>[F:21][C:4]1[CH:3]=[C:2]([C:28]2[CH:29]=[CH:30][C:25]([S:23]([CH3:22])=[O:24])=[CH:26][CH:27]=2)[CH:7]=[CH:6][C:5]=1[C:8]([N:10]1[CH2:14][CH2:13][CH2:12][C@H:11]1[CH2:15][N:16]1[CH2:20][CH2:19][CH2:18][CH2:17]1)=[O:9]
Reactant: O=C(c1ccc(Br)cc1F)N1CCC[C@H]1CN1CCCC1
Reactant: CS(=O)c1ccc(B(O)O)cc1
Product: CS(=O)c1ccc(-c2ccc(C(=O)N3CCC[C@H]3CN3CCCC3)c(F)c2)cc1

Procedure:
The title compound is prepared in a manner substantially analogous to Procedure SS starting from (4-bromo-2-fluoro-phenyl)-(2-(S)-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone and 4-Methylsulfinyl benzene boronic acid. MS (M+H) 415.1
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[CH3:11].C(Cl)(=O)C(Cl)=O.C(N(C(C)C)C(C)C)C.[Cl:27][C:28]1[CH:33]=[CH:32][C:31]([CH2:34][CH2:35][NH2:36])=[CH:30][CH:29]=1>ClCCl.CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:36][CH2:35][CH2:34][C:31]2[CH:32]=[CH:33][C:28]([Cl:27])=[CH:29][CH:30]=2)=[O:8])=[CH:4][C:3]=1[CH3:11]
Reactant: Cc1cc(C(=O)O)ccc1Br
Reactant: NCCc1ccc(Cl)cc1
Agent: O=C(Cl)C(=O)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Cc1cc(C(=O)NCCc2ccc(Cl)cc2)ccc1Br
Reaction time: 0.5 h
Yield: 48.8 %

Procedure:
To a suspension of 4-bromo-3-methylbenzoic acid (0.500 g, 2.325 mmol) in dichloromethane (10 ml) and DMF (1 drop) was added oxalyl dichloride (0.2231 ml, 2.558 mmol), and the reaction was stirred for 30 minutes. N-ethyl-N-isopropylpropan-2-amine (0.8934 ml, 5.115 mmol) and 2-(4-chlorophenyl)ethanamine (0.3557 ml, 2.558 mmol) were added, and the reaction was stirred for 1 hour at ambient temperature. The reaction was diluted with EtOAc and washed with 1M hydrochloric acid, saturated sodium bicarbonate, and saturated sodium chloride. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude material was purified by recrystallization from EtOAc and hexanes to yield 400 mg of the title compound (48.78% yield).
Reaction SMILES: C([N-]C(C)C)(C)C.[Li+].CN(C)CCN(C)C.[C:17]1([S:23]([N:26]2[C:34]3[CH:33]=[CH:32][N:31]=[C:30]([Cl:35])[C:29]=3[CH:28]=[CH:27]2)(=[O:25])=[O:24])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.Cl[C:37]([O:39][CH2:40][CH3:41])=[O:38]>C1COCC1>[CH2:40]([O:39][C:37]([C:27]1[N:26]([S:23]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)(=[O:25])=[O:24])[C:34]2[CH:33]=[CH:32][N:31]=[C:30]([Cl:35])[C:29]=2[CH:28]=1)=[O:38])[CH3:41]
Reactant: CCOC(=O)Cl
Reactant: O=S(=O)(c1ccccc1)n1ccc2c(Cl)nccc21
Agent: CC(C)[N-]C(C)C
Agent: CN(C)CCN(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: CCOC(=O)c1cc2c(Cl)nccc2n1S(=O)(=O)c1ccccc1
Temperature: -78 °C
Reaction time: 1 h
Yield: 117 %

Procedure:
Lithium diisopropylamide (3.2 mL of a 1.5 M solution in THF, 4.80 mmol) is added to a solution of tetramethylethylenediamine (0.71 mL, 4.75 mmol) and 1-benzenesulfonyl-4-chloro-1H -pyrrolo[3,2-c]pyridine (1 g, 3.42 mmol) in THF (13 mL). The resulting yellow solution is stirred at −78° C. for 1 hour, and then ethyl chloroformate (0.78 mL, 8.16 mmol) is added dropwise. The mixture is slowly brought to room temperature over a 3.5 hour period. The reaction is quenched with saturated NH4Cl solution and then diluted with ethyl acetate. The organic layer is washed with brine, dried over MgSO4, filtered and concentrated to give a light brown solid (1.46 g) as the product which is used in the subsequent step without further purification.
Reaction SMILES: Cl.[CH2:2]([O:9][C:10](=[O:23])[C@@H:11]1[CH2:15][CH2:14][CH2:13][N:12]1[C:16](=[O:22])[C@@H:17]1[CH2:21][CH2:20][CH2:19][NH:18]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N(CC)CC)C.[C:31]1([S:37](Cl)(=[O:39])=[O:38])[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>C(Cl)Cl>[CH2:2]([O:9][C:10](=[O:23])[C@@H:11]1[CH2:15][CH2:14][CH2:13][N:12]1[C:16](=[O:22])[C@@H:17]1[CH2:21][CH2:20][CH2:19][N:18]1[S:37]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)(=[O:39])=[O:38])[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1
Reactant: O=S(=O)(Cl)c1ccccc1
Reactant: O=C(OCc1ccccc1)[C@@H]1CCCN1C(=O)[C@@H]1CCCN1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(OCc1ccccc1)[C@@H]1CCCN1C(=O)[C@@H]1CCCN1S(=O)(=O)c1ccccc1
Reaction time: 1 h
Yield: 98.1 %

Procedure:
L-prolyl-L-proline benzylester hydrochloride (1.69 g, 5 mmole) was dissolved in methylene chloride (30 ml), and triethylamine (1.11 g, 11 mmole) was added thereto at -30° C. Methylene chloride (10 ml) solution of benzene sulfonyl chloride (0.86 g, 5 mmole) was added dropwise to the solution. The mixture was stirred for 1 hour at less than 0° C., and next for 5 hours at room temperature, and methylene chloride (60 ml) was added thereto. The solution was washed with 5% aqueous sodium bicarbonate (100 ml, twice), 1N aqueous hydrochloric acid (100 ml, twice) and water (100 ml) in the order given, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain N-benzenesulfonyl-L-prolyl-L-proline benzylester(yield: 2.17 g, 98.1%)
Reaction SMILES: [C:1]([O:5][C:6](=[O:40])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14](=[O:39])/[CH:15]=[CH:16]/[C@@H:17]([O:28][Si:29]([CH:36]([CH3:38])[CH3:37])([CH:33]([CH3:35])[CH3:34])[CH:30]([CH3:32])[CH3:31])[C@@H:18]([O:24][C:25](=[O:27])[CH3:26])[CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])([CH3:4])([CH3:3])[CH3:2].Cl>O1CCCC1>[C:1]([O:5][C:6](=[O:40])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C@H:14]([OH:39])/[CH:15]=[CH:16]/[C@@H:17]([O:28][Si:29]([CH:36]([CH3:38])[CH3:37])([CH:33]([CH3:35])[CH3:34])[CH:30]([CH3:32])[CH3:31])[C@@H:18]([O:24][C:25](=[O:27])[CH3:26])[CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])([CH3:3])([CH3:2])[CH3:4]
Reactant: CCCCC[C@H](OC(C)=O)[C@@H](/C=C/C(=O)CCCCCCCC(=O)OC(C)(C)C)O[Si](C(C)C)(C(C)C)C(C)C
Agent: Cl
Solvent: C1CCOC1
Product: CCCCC[C@H](OC(C)=O)[C@@H](/C=C/[C@@H](O)CCCCCCCC(=O)OC(C)(C)C)O[Si](C(C)C)(C(C)C)C(C)C
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
(S)-binal-H (0.5 M tetrahydrofuran solution, 215 μl, 0.107 mmol) was added dropwise to a tetrahydrofuran solution (300 μl) of (12R,13S)-(E)-13-acetoxy-9-oxo-12-triisopropylsiloxy 10-octadecaenoic acid t-butyl ester (18) (18.7 mg, 0.033 mmol) at −78° C. over 5 minutes under the argon atmosphere, and the mixture was stirred at −78° C. for 1 hour and 30 minutes. Hydrochloric acid (1.0 N, 1 mL) was added to the reaction solution, and the mixture was extracted with chloroform (5 mL) three times. The organic layer was washed successively with 1.0 N sodium hydroxide (5 mL) and saturated brine (5 mL), dried over sodium sulfate, and concentrated. The resulting colorless oily crude product (20 mg) was separated and purified by silica gel column chromatography (hexane:ethyl acetate=10:1) to obtain (9S,12R,13S)-(E)-13-acetoxy-9-hydroxy-12-triisopropylsiloxy-10-octadecaenoic acid t-butyl ester (19) as a colorless oily substance (18.6 mg, 99%).
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[N+:11]([O-:13])=[O:12].[C:14](Cl)(=O)C(Cl)=O.C(N(CC)CC)C.CO.C(=O)(O)[O-].[Na+]>ClCCl.CN(C)C=O>[CH3:14][O:7][C:6](=[O:8])[C:5]1[CH:9]=[CH:10][C:2]([F:1])=[C:3]([N+:11]([O-:13])=[O:12])[CH:4]=1
Reactant: O=C(Cl)C(=O)Cl
Reactant: O=C(O)c1ccc(F)c([N+](=O)[O-])c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: CO
Product: COC(=O)c1ccc(F)c([N+](=O)[O-])c1
Temperature: 0 °C
Reaction time: 2 h
Yield: 98.6 %

Procedure:
To a solution of 4-fluoro-3-nitro-benzoic acid (25 g, 0.135 mol) in dichloromethane (250 ml) at 23° C. was added dimethylformamide (0.5 ml) followed by dropwise addition of oxalyl chloride (15 ml, 0.172 mol). After stirring for 2 hours an aliquot was removed and confirmed to be product by 1H NMR. The entire sample was then concentrated under reduced pressure, diluted with dichloromethane (250 ml) and cooled to 0° C. The sample was then treated with a solution of triethylamine (37 ml, 0.266 mol) and methyl alcohol (43 ml, 0.939 mol) in dichloromethane (50 ml) added dropwise over 30 minutes. The reaction was allowed to warm to 23° C. After 2 hours the reaction was poured onto aqueous sodium bicarbonate and extracted with dichloromethane. The organic layer was dried with sodium sulfate and concentrated in vacuo to give 26.5 g of 4-fluoro-3-nitro-benzoic acid methyl ester as a solid.
Reaction SMILES: [N:1]1([CH2:6][C:7]([OH:9])=O)[CH:5]=[N:4][N:3]=[N:2]1.[Cl:10]C(N(C)C)=C(C)C>C(Cl)Cl>[N:1]1([CH2:6][C:7]([Cl:10])=[O:9])[CH:5]=[N:4][N:3]=[N:2]1
Reactant: O=C(O)Cn1cnnn1
Reactant: CC(C)=C(Cl)N(C)C
Solvent: ClCCl
Product: O=C(Cl)Cn1cnnn1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
1.58 g of 2-(tetrazol-1-yl)-acetic acid are suspended in 27 ml of absolute methylene chloride, and 1.9 ml of 1-chloro-1-dimethylaminoisobutene (CDIB) are added. After stirring for 30 minutes at room temperature, a further 0.5 ml of CDIB is added and stirring is continued for a further 90 minutes. This solution of the acid chloride [IR (methylene chloride): 3.20, 5.57 μm] is further reacted directly.
Reaction SMILES: Cl.[N+:2]([C:5]1[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=1[NH2:7])([O-:4])=[O:3].[CH2:12](O)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[OH-].[Na+]>[Cl-].[Zn+2].[Cl-].CCOCC.O>[CH2:12]([C:10]1[CH:9]=[CH:8][C:6]([NH2:7])=[C:5]([N+:2]([O-:4])=[O:3])[CH:11]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: Nc1ccccc1[N+](=O)[O-]
Reactant: OCc1ccccc1
Agent: Cl
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: CCOCC
Product: Nc1ccc(Cc2ccccc2)cc1[N+](=O)[O-]

Procedure:
To 20.4 parts of 36% w/w hydrochloric acid in which had previously been dissolved 13.4 parts of anhydrous zinc chloride are added 27.6 parts of o-nitro-aniline and 10.8 parts of benzyl alcohol. This mixture is stirred under reflux temperature for 6 hours and then poured into a hot solution of 50 parts of sodium hydroxide in 100 parts of water. After allowing the decomposed reaction mixtures to cool the organic phase is extracted with ether, and the ether solution washed with water, the ether evaporated and the residue distilled to give a fraction with boiling point 192°-8° C. at 0.4 millibars. This fraction after dilution with 40°-60° petroleum ether containing a little ether yields 4-benzyl-2-nitro-aniline m.p. 80°-3° C.