Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:3]1[CH:10]=[CH:9][C:6]([CH:7]=[O:8])=[CH:5][CH:4]=1)[CH3:2].[CH2:11]([Mg]Br)[CH2:12][CH3:13]>C(OCC)C>[CH2:1]([C:3]1[CH:10]=[CH:9][C:6]([CH:7]([OH:8])[CH2:11][CH2:12][CH3:13])=[CH:5][CH:4]=1)[CH3:2]
Reactant: CCC[Mg]Br
Reactant: CCc1ccc(C=O)cc1
Solvent: CCOCC
Product: CCCC(O)c1ccc(CC)cc1
Temperature: 0 °C

Procedure:
To a flame-dried flask under an argon atmosphere is added 0.69 mL of commercially available 4-ethylbenzaldehyde and charged with 15 mL of diethyl ether. The solution is cooled to 0° C. and is treated with 3.0 mL (2.0M in diethyl ether) of propylmagnesium bromide. The reaction mixture is left to warm to room temperature overnight and then quenched by the addition of aqueous ammonium chloride. After dilution with diethyl ether the phases are separated; the organic layer is washed with saturated ammonium chloride, dried (magnesium sulfate) and finally concentrated under reduced pressure. The residue is flash column chromatographed using 25% to 30% diethyl ether in hexane to yield 1.08 g of the title product as a clear, colorless oil.
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:14](=[O:22])[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([OH:21])[CH:16]=1.[N:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[CH2:29]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1(C)C=CC=CC=1>[NH2:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:14](=[O:22])[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH2:29][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][N:23]=2)[CH:16]=1
Reactant: OCc1ccccn1
Reactant: Nc1c(C(=O)c2cccc(O)c2)cnn1-c1ccc(F)cc1
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: Nc1c(C(=O)c2cccc(OCc3ccccn3)c2)cnn1-c1ccc(F)cc1
Reaction time: 16 h

Procedure:
5-Amino-1-(4-fluorophenyl)-4-[3-hydroxybenzoyl]pyrazole, from Example 10, step 2, (0.5 g, 1.68 mmol), 2-pyridylcarbinol (0.81 mL, 8.41 mmol), triphenylphosphine (1.81 g, 6.9 mmol), and diethylazodicarboxylate (1.09 mL, 6.9 mmol)) were combined in toluene (50 mL). The reaction mixture was stirred for 16 hours then quenched with a saturated aqueous solution of NH4Cl and extracted three times with ethyl acetate. The product was then extracted from the ethyl acetate into a 10% aqueous solution of HCl. The aqueous layer was then neutralized with NaOH and extracted with ethyl acetate. The organic extracts were dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by column chromatography on silica gel using 1:1 hexane/ethyl acetate to give 0.165 g of 5-amino-1-(4-fluorophenyl)-4-[3-(pyridin-2-ylmethoxy)benzoyl]pyrazole (mpt. 176.1-177.3° C.).
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[CH:12][C:7]([C:8]([NH:10][NH2:11])=[O:9])=[CH:6][CH:5]=1)([O-:3])=[O:2].[C:14](OC)(OC)(OC)[CH3:15]>>[CH3:14][C:15]1[O:9][C:8]([C:7]2[CH:12]=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)=[N:10][N:11]=1
Reactant: COC(C)(OC)OC
Reactant: NNC(=O)c1ccc([N+](=O)[O-])cc1
Product: Cc1nnc(-c2ccc([N+](=O)[O-])cc2)o1
Temperature: 25 °C

Procedure:
4-Nitro-benzoic acid hydrazide (1.0 g, 5.6 mmol) was heated to reflux in trimethyl orthoacetate for 4 days. After cooling to RT, the mixture was triturated with hexanes and the title compound collected by filtration (0.93 g). MS (ESI+) for m/z 206 (M+H)+.
Reaction SMILES: [F:1][C:2]1[C:7]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])=[N:6][CH:5]=[C:4]([C:16]2[CH:21]=[CH:20][C:19]([O:22][Si](C(C)(C)C)(C3C=CC=CC=3)C3C=CC=CC=3)=[CH:18][CH:17]=2)[N:3]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[F:1][C:2]1[C:7]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15])=[N:6][CH:5]=[C:4]([C:16]2[CH:17]=[CH:18][C:19]([OH:22])=[CH:20][CH:21]=2)[N:3]=1
Reactant: CCCCCCCCc1ncc(-c2ccc(O[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)cc2)nc1F
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: CCCCCCCCc1ncc(-c2ccc(O)cc2)nc1F
Yield: 90.7 %

Procedure:
11.82 g (21.87 mmol) of 2-fluoro-3-octyl-6-(4-tert-butyldiphenylsilyloxyphenyl)pyrazine and 43.74 ml of a 1 molar solution of tetra-n-butylammonium fluoride in tetrahydrofuran are stirred for 1 hour at room temperature in 140 ml of tetrahydrofuran. The reaction mixture is partitioned between aqueous sodium chloride solution and ether, the organic phase is washed with aqueous sodium chloride solution, dried over sodium sulfate, and freed from solvent, and the product is recrystallized from n-hexane. 6.00 g of 2-fluoro-3-octyl-6-(4-hydroxyphenyl) pyrazine are obtained. ##STR25## 4e
Reaction SMILES: [C:1]([CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[NH:10][C:11](=O)[C:12]1[CH:17]=[CH:16][CH:15]=[N:14][CH:13]=1)#[N:2].[H-].[Na+]>CN(C=O)C.C(OCC)(=O)C>[N:14]1[CH:15]=[CH:16][CH:17]=[C:12]([C:11]2[NH:10][C:5]3[C:4]([C:3]=2[C:1]#[N:2])=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH:13]=1
Reactant: N#CCc1ccccc1NC(=O)c1cccnc1
Agent: [H-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: N#Cc1c(-c2cccnc2)[nH]c2ccccc12
Temperature: 130 °C
Reaction time: 18 h

Procedure:
N-(2-cyanomethyl-phenyl)-nicotinamide (0.095 g, 0.384 mmol) is dissolved in DMF (3 mL). NaH (60%, 0.015 g, 0.384 mmol) is added and the mixture is heated to 130° C. After 18 h, the mixture is cooled down, diluted with ethyl acetate, and washed with 1M aqueous sodium hydroxide. The combined washings are back-extracted with ethyl acetate. The combined organic phase is dried over magnesium sulfate, filtered and concentrated in vacuo. The residue is purified by silica gel flash chromatography (dichloromethane-methanol, 99:1 to 19:1) to give 2-pyridin-3-yl-1H-indole-3-carbonitrile as a brown solid. 1H NMR (400 MHz, MeOD) δ ppm 7.29-7.32 (m, 1H), 7.34-7.39 (m, 1H), 7.57 (d, J=8.0 Hz, 1H), 7.66 (dd, J=8.0, 4.9 Hz, 1H), 7.70 (d, J=7.8 Hz, 1H), 8.39-8.44 (m, 1H), 8.68 (dd, J=4.8, 1.5 Hz, 1H), 9.15 (d, J=1.5 Hz, 1H).
Reaction SMILES: C(O)(C(F)(F)F)=O.[F:8][C:9]([F:34])([F:33])[C:10]1[CH:15]=[C:14]([N:16]2[CH2:32][CH2:31][C:19]3([CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21][CH2:20]3)[CH2:18][CH2:17]2)[CH:13]=[CH:12][N:11]=1>C(Cl)Cl>[F:34][C:9]([F:8])([F:33])[C:10]1[CH:15]=[C:14]([N:16]2[CH2:17][CH2:18][C:19]3([CH2:23][NH:22][CH2:21][CH2:20]3)[CH2:31][CH2:32]2)[CH:13]=[CH:12][N:11]=1
Reactant: CC(C)(C)OC(=O)N1CCC2(CCN(c3ccnc(C(F)(F)F)c3)CC2)C1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: FC(F)(F)c1cc(N2CCC3(CCNC3)CC2)ccn1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
TFA (1.5 ml) is added to a solution of tert-butyl 8-(2-(trifluoromethyl)pyridin-4-yl)-2,8-diazaspiro[4.5]decane-2-carboxylate (0.64 mmol, 1.0 eq.) in methylene chloride (5 ml) at 0° C. and the reaction mixture is stirred at 25° C. for 1 h. When the reaction was complete, the solvent was removed in vacuo in order to obtain the desired amine (AMN-26).
Reaction SMILES: [CH3:1][O:2][N:3]=[CH:4][C:5]([O-:7])=O.[Cl:8][C:9]1[C:15]([O:16][CH2:17][C:18]#[CH:19])=[CH:14][C:12]([NH2:13])=[C:11]([F:20])[CH:10]=1.P(Cl)(Cl)Cl.O.C(=O)(O)[O-].[Na+]>C1(C)C(C)=CC=CC=1>[Cl:8][C:9]1[C:15]([O:16][CH2:17][C:18]#[CH:19])=[CH:14][C:12]([NH:13][C:5](=[O:7])[CH:4]=[N:3][O:2][CH3:1])=[C:11]([F:20])[CH:10]=1
Reactant: CON=CC(=O)[O-]
Reactant: C#CCOc1cc(N)c(F)cc1Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: Cc1ccccc1C
Solvent: ClP(Cl)Cl
Product: C#CCOc1cc(NC(=O)C=NOC)c(F)cc1Cl
Yield: 49.1 %

Procedure:
0.58 g of the obtained 2-(methoxyimino)acetate was dissolved in 30 ml of xylene and 1.00 g of 4-chloro-2-fluoro-5-propargyloxyaniline was added thereto. 0.17 ml of phosphorus trichloride was then added to the resulting solution and the entire mixture was heated to reflux for 1 hour. After cooling the resulting reaction solution, sodium bicarbonate water was added thereto and the resultant solution was then extracted with ethyl acetate. After washing with saturated saline, the organic layer was dried with anhydrous magnesium sulfate and filtered. The concentrate obtained by evaporating solvents from the filtrate under reduced pressure was washed with a mixed solvent of ether-normal hexane to obtain 0.70 g of N-(4-chloro-2-fluoro-5-propargyloxyphenyl)-2-(methoxyimino)acetamide (yield 49%).
Reaction SMILES: [CH2:1]([N:3]([CH3:7])[C:4](Cl)=[O:5])[CH3:2].[OH:8][C:9]1[CH:17]=[C:16]2[C:12]([CH2:13][CH2:14][C:15]2=[O:18])=[CH:11][CH:10]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[O:18]=[C:15]1[C:16]2[C:12](=[CH:11][CH:10]=[C:9]([O:8][C:4](=[O:5])[N:3]([CH2:1][CH3:2])[CH3:7])[CH:17]=2)[CH2:13][CH2:14]1
Reactant: O=C1CCc2ccc(O)cc21
Reactant: CCN(C)C(=O)Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCN(C)C(=O)Oc1ccc2c(c1)C(=O)CC2
Temperature: 25 °C
Yield: 81.2 %

Procedure:
Ethylmethyl carbamyl chloride (15.5 g, 127.57 mmol) was added to a stirred suspension of 6-hydroxy-1-indanone (17.2 g, 116.1 mmol) and potassium carbonate (31.8 g, 188 mmol) in acetonitrile (800 mL) at room temperature over a period of 15 minutes. The reaction mixture was heated to reflux and refluxed for 18 hours. The reaction mixture was cooled to ambient temperature, the solvent evaporated and the residue was diluted with water (250 mL) and extracted three times with toluene (250 mL). The combined organic phase was dried on MgSO4 and toluene was evaporated in a rotary evaporator. The crude crystalline product was purified by crystallization from 2-propanol (200 mL), collected by filtration, and dried under vacuum at 50° C. to afford the title compound (22 g, 81.5%). 1H NMR (300 MHz, CDCl3) δ ppm 7.47-7.44 (2H, m, Ar), 7.36 (1H, dd, J 8.4 and 2.1, Ar), 3.52-3.37 (2H, m, NCH2CH3), 3.14-3.108 [2H, m, OCCH2CH2 and incl. NCH3 (two rotamers), at 3.08 and 2.99 (3H, s, Me)], 2.74-2.71 (2H, m, OCCH2CH2) and 1.25 and 1.19 (two rotamers) (3H,two triplets, J 6.9). Mass Spectrum (FAB+) [MH+]=234
Reaction SMILES: [N+]([C:4]1[C:17]2[C:16](=[O:18])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:19])[C:8]=2[CH:7]=[CH:6][CH:5]=1)([O-])=O.S([O-])([O-])=O.[Na+].[Na+]>O>[CH:11]1[C:10]2[C:9](=[O:19])[C:8]3[C:17](=[CH:4][CH:5]=[CH:6][CH:7]=3)[C:16](=[O:18])[C:15]=2[CH:14]=[CH:13][CH:12]=1
Reactant: O=C1c2ccccc2C(=O)c2c1cccc2[N+](=O)[O-]
Agent: O=S([O-])[O-]
Agent: [Na+]
Solvent: O
Product: O=C1c2ccccc2C(=O)c2ccccc21

Procedure:
50 g of a crude 1-nitroanthraquinone manufactured according to Example 1 are stirred with 20 g of sodium sulphite in 400 ml of water for 6 hours at the reflux temperature. After filtration, washing and drying, 38.2 g of 1-nitroanthraquinone of the composition indicated in Table A are obtained (= 69% of theory, relative to anthraquinone employed).
Reaction SMILES: [CH3:1][O:2][C:3]([CH:5]1[CH2:7][N@@:6]1[S:8]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[Cl:17])(=[O:10])=[O:9])=[O:4].[Cl:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[N:25]=[C:26]=[O:27].[I-].[Na+]>>[CH3:1][O:2][C:3]([C@@H:5]1[CH2:7][N:6]([S:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[Cl:17])(=[O:9])=[O:10])[C:26](=[O:27])[N:25]1[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=1[Cl:18])=[O:4]
Reactant: O=C=Nc1ccccc1Cl
Reactant: COC(=O)C1C[N@@]1S(=O)(=O)c1ccccc1Cl
Agent: COC(=O)C1C[N@]1S(=O)(=O)c1ccccc1Cl
Agent: [I-]
Agent: [Na+]
Product: COC(=O)[C@@H]1CN(S(=O)(=O)c2ccccc2Cl)C(=O)N1c1ccccc1Cl

Procedure:
In analogy to example 1, step 3, (S)-1-(2-chloro-benzenesulfonyl)-aziridine-2-carboxylic acid methyl ester was reacted with 2-chlorophenylisocyanate and sodium iodide to give (S)-1-(2-chloro-benzenesulfonyl)-3-(2-chloro-phenyl)-2-oxo-imidazolidine-4-carboxylic acid methyl ester as a colorless foam.
Reaction SMILES: [C:1]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1O)=[CH:13][C:12]([O:17][CH3:18])=[C:11]([O:19][CH3:20])[CH:10]=2)([O:3][CH2:4][CH3:5])=[O:2].P(Cl)(Cl)([Cl:23])=O.[OH-].[NH4+]>>[C:1]([C:6]1[CH:7]=[N:8][C:9]2[C:14]([C:15]=1[Cl:23])=[CH:13][C:12]([O:17][CH3:18])=[C:11]([O:19][CH3:20])[CH:10]=2)([O:3][CH2:4][CH3:5])=[O:2]
Reactant: CCOC(=O)c1cnc2cc(OC)c(OC)cc2c1O
Reactant: O=P(Cl)(Cl)Cl
Agent: [NH4+]
Agent: [OH-]
Product: CCOC(=O)c1cnc2cc(OC)c(OC)cc2c1Cl
Temperature: 10 °C
Reaction time: 0.5 h

Procedure:
A mixture of 28.8 g of 3-carbethoxy-4-hydroxy-6,7-dimethoxyquinoline and 16.6 ml of phosphorous oxychloride was stirred at 1 10° C. for 30 min, cooled to 0° C., and treated with a mixture of ice and ammonium hydroxide. The resulting grey solid was filtered, washed with water and ether, and dried, mp 147-150° C.
Reaction SMILES: [CH3:1][CH:2]([N:8]([CH2:13][CH:14]([O:18][CH2:19][CH3:20])[O:15]CC)[C:9](=[O:12])[CH2:10][Cl:11])[CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].C(O)CO.C1(C)C(S(O)(=O)=O)=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)C>[CH3:1][CH:2]([N:8]([CH2:13][CH:14]1[O:15][CH2:20][CH2:19][O:18]1)[C:9](=[O:12])[CH2:10][Cl:11])[CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: CCCCCC(C)N(CC(OCC)OCC)C(=O)CCl
Agent: Cc1ccccc1S(=O)(=O)O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: OCCO
Product: CCCCCC(C)N(CC1OCCO1)C(=O)CCl

Procedure:
N-(1-Methylhexyl)-N-(2,2-diethoxyethyl)-α-chloroacetamide (10 grams), ethylene glycol (2.0 grams) and trace amounts of toluenesulfonic acid were charged into a glass reaction vessel equipped with a mechanical stirrer, thermometer and reflux condenser. The reaction mixture was heated at reflux until no more ethanol was given off. After this time sodium carbonate (1 gram) was added to the mixture with stirring and the resulting mixture was distilled to yield the desired product N-(1-methylhexyl)-N-(1,3-dioxolan-2-ylmethyl)-α-chloroacetamide having a boiling point of 173° C. at 1 mm of Hg pressure.
Reaction SMILES: CI.[C:3]([C:6]1[CH:7]([C:24]2[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][C:25]=2[Br:32])[NH:8][C:9](=[O:23])[N:10]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=2)[C:11]=1[CH3:12])(=[O:5])[CH3:4].[C:33](=O)([O-])[O-].[Cs+].[Cs+].O>CN(C)C=O.C(OCC)(=O)C>[C:3]([C:6]1[CH:7]([C:24]2[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[CH:26][C:25]=2[Br:32])[N:8]([CH3:33])[C:9](=[O:23])[N:10]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:20])([F:21])[F:22])[CH:14]=2)[C:11]=1[CH3:12])(=[O:5])[CH3:4]
Reactant: O=C([O-])[O-]
Reactant: CC(=O)C1=C(C)N(c2cccc(C(F)(F)F)c2)C(=O)NC1c1ccc(C#N)cc1Br
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: CI
Product: CC(=O)C1=C(C)N(c2cccc(C(F)(F)F)c2)C(=O)N(C)C1c1ccc(C#N)cc1Br
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Methyliodide (c=2 mol/L, 3.24 mL, 6.48 mmol) is added to a suspension of 4-[5-acetyl-6-methyl-2-oxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4-tetrahydro-pyrimidin-4-yl]-3-bromo-benzonitrile (intermediate 3) (2.48 g, 5.18 mmol) and cesium carbonate (2.20 g, 6.74 mmol) in N,N-dimethylformamide (50.0 mL). The reaction mixture is stirred at room temperature overnight. Water and ethyl acetate are added and the phases are separated. The aqueous phase is extracted twice with ethyl acetate and the combined organic phases are washed with saturated sodium chloride solution, dried over MgSO4 and concentrated. The residue is purified by reversed phase HPLC. Yield: 2.64 g. ESI mass spectrum: [(79Br)-M+H]+=492, [(81Br)-M+H]+=494; Retention time HPLC: 1.06 min (HPLC method Z018_S04).
Reaction SMILES: CO[C:3](=[O:23])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]2[C:13]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[N:14][O:15][CH:16]=2)=[N:6][CH:5]=1.[NH2:24][CH:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1>>[C:17]1([C:13]2[C:12]([CH2:11][O:10][C:7]3[CH:8]=[CH:9][C:4]([C:3]([NH:24][CH:25]4[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[O:23])=[CH:5][N:6]=3)=[CH:16][O:15][N:14]=2)[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: COC(=O)c1ccc(OCc2conc2-c2ccccc2)nc1
Reactant: NC1CCOCC1
Product: O=C(NC1CCOCC1)c1ccc(OCc2conc2-c2ccccc2)nc1
Yield: 73 %

Procedure:
As described for example 321d, 6-(3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid methyl ester (67 mg, 0.21 mmol) was converted, using 4-aminotetrahydropyran instead of isopropylamine, to the title compound (60 mg, 73%) which was obtained as an off white solid. MS: m/e=380.2 [M+H]+.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[CH2:9][O:8][B:7]([OH:10])[C:6]=2[CH:11]=1.CN1CCOCC1.[O:19]=[C:20]([CH3:40])[CH2:21][CH2:22][C:23]1[CH:28]=[C:27]([NH:29][C:30](=[O:35])[C:31]([F:34])([F:33])[F:32])[CH:26]=[CH:25][C:24]=1[S:36](Cl)(=[O:38])=[O:37]>CC#N>[F:34][C:31]([F:32])([F:33])[C:30]([NH:29][C:27]1[CH:26]=[CH:25][C:24]([S:36](=[O:37])(=[O:38])[NH:1][C:2]2[CH:3]=[CH:4][C:5]3[CH2:9][O:8][B:7]([OH:10])[C:6]=3[CH:11]=2)=[C:23]([CH2:22][CH2:21][C:20](=[O:19])[CH3:40])[CH:28]=1)=[O:35]
Reactant: Nc1ccc2c(c1)B(O)OC2
Reactant: CC(=O)CCc1cc(NC(=O)C(F)(F)F)ccc1S(=O)(=O)Cl
Solvent: CC#N
Solvent: CN1CCOCC1
Product: CC(=O)CCc1cc(NC(=O)C(F)(F)F)ccc1S(=O)(=O)Nc1ccc2c(c1)B(O)OC2
Temperature: 25 °C
Reaction time: 2 h
Yield: 53.2 %

Procedure:
To a solution of 6-amino-3H-benzo[c][1,2]oxaborol-1-ol (0.37 g, 2 mmol) and NMM (0.76 g, 7 mmol) in CH3CN (50 mL) was added a solution of 2-(3-oxobutyl)-4-(2,2,2-trifluoroacetamido)benzene-1-sulfonyl chloride (0.9 g, 2 mmol) in CH3CN (30 mL) dropwise at 0° C. The reaction mixture was stirred at room temperature for 2 hrs, then the reaction mixture was concentrated in vacuo, the residue was diluted with water and extracted with EtOAc, the organics was dried over Na2SO4, concentrated to give the crude product, the crude was purified by pre-HPLC (column: Luna 300×50.0 mm, 10 um; liquid phase: [A-H2O+0.05% TFA; B-MeCN] B %: 24%-51%, 23 min) to give 2,2,2-trifluoro-N-(4-(N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)-3-(3-oxobutyl)phenyl)acetamide (0.5 g, yield 42%) as yellow solid.
Reaction SMILES: CC1(C)C(C)(C)OB([C:9]2[CH:10]=[CH:11][C:12]3[O:16][C:15]([CH:17]4[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]4)=[N:14][C:13]=3[CH:30]=2)O1.Br[C:33]1[CH:38]=[CH:37][C:36]([O:39][CH:40]([CH3:42])[CH3:41])=[C:35]([F:43])[CH:34]=1>>[F:43][C:35]1[CH:34]=[C:33]([C:9]2[CH:10]=[CH:11][C:12]3[O:16][C:15]([CH:17]4[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:27])([CH3:29])[CH3:28])=[O:24])[CH2:19][CH2:18]4)=[N:14][C:13]=3[CH:30]=2)[CH:38]=[CH:37][C:36]=1[O:39][CH:40]([CH3:42])[CH3:41]
Reactant: CC(C)Oc1ccc(Br)cc1F
Reactant: CC(C)(C)OC(=O)N1CCC(c2nc3cc(B4OC(C)(C)C(C)(C)O4)ccc3o2)CC1
Product: CC(C)Oc1ccc(-c2ccc3oc(C4CCN(C(=O)OC(C)(C)C)CC4)nc3c2)cc1F
Yield: 15.7 %

Procedure:
Following the General Procedure-3, the titled compound (25 mg) was prepared from Intermediate 8 (150 mg, 0.35 mmol) and 4-bromo-2-fluoro-1-isopropoxybenzene (81 mg, 0.35 mmol) as a white solid. M.P.: 124-128° C. 1H-NMR (δ ppm, CDCl3, 400 MHz): 7.81 (d, J 1.4, 1H), 7.53-7.45 (m, 2H), 7.35-7.27 (m, 2H), 7.05 (t, J 8.6, 1H), 4.58 (septet, J 6.1, 1H), 4.15 (d, J 10.4, 2H), 3.20-3.10 (m, 1H), 2.99 (t, J 11.7, 2H), 2.15 (dd, J 2.8, 13.4, 2H), 1.97-1.86 (m, 2H), 1.56 (s, 9H), 1.39 (d, J 6.1, 6H).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:20])[CH:5]([CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[N:6]1[CH:10]=[C:9]([N+:11]([O-])=O)[N:8]=[CH:7]1)[CH3:2].[H][H]>[Pd]>[CH2:1]([O:3][C:4](=[O:20])[CH:5]([CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[N:6]1[CH:10]=[C:9]([NH2:11])[N:8]=[CH:7]1)[CH3:2]
Reactant: [H][H]
Reactant: CCCCCCC(C(=O)OCC)n1cnc([N+](=O)[O-])c1
Agent: [Pd]
Product: CCCCCCC(C(=O)OCC)n1cnc(N)c1
Yield: 100.5 %

Procedure:
A mixture of 5.9 g of 4-nitro-α-hexyl-1H-imidazole-1-acetic acid ethyl ester, 3 g of palladium-on-carbon and 150 ml of absolute alcohol were subjected to catalytic hydrogenation. Both theoretical and actual hydrogen uptake was 73 pounds. The catalyst was removed by filtration and the filtrate concentrated in vacuo to provide 5.3 g of the desired title intermediate which was used directly.
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].[CH3:5][O:6][C:7]1[CH:15]=[CH:14][C:10]([C:11](Cl)=[O:12])=[CH:9][CH:8]=1.[C:16]1([C:22]2[C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=3[S:24][CH:23]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.Cl>ClCCCl>[CH3:5][O:6][C:7]1[CH:15]=[CH:14][C:10]([C:11]([C:23]2[S:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[C:22]=2[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:12])=[CH:9][CH:8]=1
Reactant: COc1ccc(C(=O)Cl)cc1
Reactant: c1ccc(-c2csc3ccccc23)cc1
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCCl
Product: COc1ccc(C(=O)c2sc3ccccc3c2-c2ccccc2)cc1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 70 %

Procedure:
To a stirred slurry of 14.6 g. (0.11 mole) of aluminum chloride in 1,2-dichloroethane maintained at 0° C. were added 18.7 g. (0.11 mole) of 4-methoxybenzoyl chloride. The mixture was stirred at 0° C. for 10 minutes, and 21.0 g. (0.1 mole) of 3-phenylbenzothiophene in 1,2-dichloroethane were added. The mixture was stirred for two hours, the temperature being maintained at 0° C. The reaction mixture then was poured into a mixture of hydrochloric acid in ice. The resulting mixture was extracted with ether. The ether extract was washed with water, dilute aqueous sodium bicarbonate, and water. The ether layer was dried over magnesium sulfate, and the ether solvent was evaporated. The residue was dissolved in ethanol. The ethanol solution was filtered and maintained at 5° C. for three days. The resulting crystals were filtered and washed with ethanol and petroleum ether to obtain 23.7 g. (70 percent) of the title compound, m.p. 94°-95° C. The nmr spectrum was consistent with the structure of the title compound.
Reaction SMILES: [N+:1]([C@@H:4]1[CH2:9][C:8]([C:10]([O:12][CH2:13]C)=[O:11])=[CH:7][CH2:6][C@H:5]1[C:15]1[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:16]=1[F:23])([O-])=O>C(O)C.Cl.[Fe]>[NH2:1][C@@H:4]1[CH2:9][C:8]([C:10]([O:12][CH3:13])=[O:11])=[CH:7][CH2:6][C@H:5]1[C:15]1[CH:20]=[C:19]([F:21])[C:18]([F:22])=[CH:17][C:16]=1[F:23]
Reactant: CCOC(=O)C1=CC[C@@H](c2cc(F)c(F)cc2F)[C@H]([N+](=O)[O-])C1
Agent: [Fe]
Agent: Cl
Solvent: CCO
Product: COC(=O)C1=CC[C@@H](c2cc(F)c(F)cc2F)[C@H](N)C1
Temperature: 45 °C
Reaction time: 1 h
Yield: 75.8 %

Procedure:
A mixture of trans-ethyl 5-nitro-4-(2,4,5-trifluorophenyl)cyclohex-1-enecarboxylate (500 g, 1.59 mol) and Fe powder (90 g, 1.6 mol) in ethanol (3.2 L) and 2 M HCl (3.2 L) was heated to 45° C., whereupon the internal temperature of the reaction increased to 65° C. over the course of 0.5 hours. After the internal temperature had fallen to 45° C., a second portion of Fe powder (135 g, 2.4 mol) was added, resulting in an increase in internal temperature to 73° C. After thirty minutes, a third aliquot of Fe powder (90 g, 1.6 mol) was added, and the reaction was allowed to stir for one hour, after which the heating bath was removed. Ammonium hydroxide (˜100 mL) was then added to the ambient mixture until the pH was 8. The mixture was filtered though celite, eluting with boiling EtOH. The ethanol was removed under reduced pressure, and the aqueous was acidified with concentrated HCl to pH ˜3. The aqueous layer was then washed with diethyl ether (3×1 L), and the combined dark organic layers were discarded. The aqueous layer was basified with ammonium hydroxide, and the resulting emulsion was filtered through celite (eluting with hot EtOH). The filtrate was concentrated under reduced pressure, and the residue was partitioned between ethyl acetate and saturated aqueous NaHCO3. The layers were separated, and the organic was washed with saturated aqueous NaHCO3, dried over Na2SO4, filtered, and concentrated under reduced pressure to give the title compound as an oil (344 g, 75%).
Reaction SMILES: [CH3:1][N:2]1[C:6]2[CH:7]=[CH:8][C:9]([C:11]([OH:13])=O)=[CH:10][C:5]=2[N:4]=[N:3]1.[NH:14]1[CH2:19][CH2:18][CH2:17][C@@H:16]2[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:25]=3[CH2:26][C@H:15]12.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>>[N:14]1([C:11]([C:9]2[CH:8]=[CH:7][C:6]3[N:2]([CH3:1])[N:3]=[N:4][C:5]=3[CH:10]=2)=[O:13])[CH2:19][CH2:18][CH2:17][C@@H:16]2[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:25]=3[CH2:26][C@H:15]12
Reactant: Cn1nnc2cc(C(=O)O)ccc21
Reactant: c1ccc2c(c1)C[C@@H]1NCCC[C@H]21
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Product: Cn1nnc2cc(C(=O)N3CCC[C@@H]4c5ccccc5C[C@@H]43)ccc21
Yield: 65 %

Procedure:
The title compound is prepared from 1-methyl-1H-benzotriazole-5-carboxylic acid and cis-2,3,4,4a,9,9a-hexahydro-1H-indeno[2,1-b]pyridine following a procedure analogous to that described in Example 1 [2-(7-aza-1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexa-fluorophosphate is used]. Yield: 65% of theory; LC (method 4): tR=1.88 min; Mass spectrum (ESI+): m/z=333 [M+H]+.