Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].S(Cl)(Cl)=O.[CH2:15](O)[CH3:16]>>[CH2:15]([O:5][C:4](=[O:6])[C:3]1[CH:7]=[CH:8][CH:9]=[N:10][C:2]=1[Cl:1])[CH3:16]
Reactant: O=C(O)c1cccnc1Cl
Reactant: CCO
Solvent: O=S(Cl)Cl
Product: CCOC(=O)c1cccnc1Cl

Procedure:
To a solution 2-Chloro-nicotinic acid (12.5 g) in Ethanol (250 ml) was added thionyl chloride (5.77 ml) dropwise and refluxed for 1.5 hours. The mixture was concentrated to remove ethanol and diluted with 300 ml water. Solid sodium bicarbonate was added to adjust the solution to pH 8.0. This was extracted with ethyl acetate, washed with water, saturated bicarbonate solution, water and brine, dried over Na2SO4, filtered and concentrated to a yellow liquid (10.0 g). MW 185.61; MS (m/e) 185 (M+).
Reaction SMILES: [NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:9][CH:10]=2)[C:5]([N+:17]([O-:19])=[O:18])=[CH:4][CH:3]=1.[Br:20]N1C(=O)CCC1=O.O.C(Cl)Cl>C(O)(=O)C>[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:12][C:13]([CH3:16])([CH3:14])[CH3:15])=[CH:9][CH:10]=2)[C:5]([N+:17]([O-:19])=[O:18])=[CH:4][C:3]=1[Br:20]
Reactant: CC(C)(C)Oc1ccc2c(N)ccc([N+](=O)[O-])c2c1
Reactant: O=C1CCC(=O)N1Br
Solvent: CC(=O)O
Solvent: O
Solvent: ClCCl
Product: CC(C)(C)Oc1ccc2c(N)c(Br)cc([N+](=O)[O-])c2c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a stirred solution of 1-amino-6-tert-butoxy-4-nitronaphthalene, as described above in Step E, (2.02 g, 7.76 mmol) in acetic acid (55 mL) was added N-bromosuccinimide (1.45 g, 8.15 mmol), portionwise. The reaction mixture was stirred at ambient temperature for 1 hour, then H2O (150 mL) and CH2Cl2 (300 mL) were added and the organic layer was extracted. The organic extract was washed with saturated aqueous Na2CO3 (2×100 mL), then brine (100 mL), then dried over Na2SO4, filtered, and concentrated in vacuo. The residue was triturated with hexane-Et2O to provide the titled product.
Reaction SMILES: [H-].[Na+].[CH3:3][S:4]([NH2:7])(=[O:6])=[O:5].[F:8][CH:9]1[CH2:12][N:11]([C:13]2[CH:14]=[C:15]([CH:19]3[C:28]([CH3:30])([CH3:29])[CH2:27][C:26]4[C:21](=[CH:22][CH:23]=[C:24]([C:31](O)=[O:32])[CH:25]=4)[NH:20]3)[CH:16]=[CH:17][CH:18]=2)[CH2:10]1.C(N1C=CN=C1)(N1C=CN=C1)=O>CN(C)C=O>[F:8][CH:9]1[CH2:12][N:11]([C:13]2[CH:14]=[C:15]([CH:19]3[C:28]([CH3:29])([CH3:30])[CH2:27][C:26]4[C:21](=[CH:22][CH:23]=[C:24]([C:31]([NH:7][S:4]([CH3:3])(=[O:6])=[O:5])=[O:32])[CH:25]=4)[NH:20]3)[CH:16]=[CH:17][CH:18]=2)[CH2:10]1
Reactant: CC1(C)Cc2cc(C(=O)O)ccc2NC1c1cccc(N2CC(F)C2)c1
Reactant: CS(N)(=O)=O
Agent: O=C(n1ccnc1)n1ccnc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC1(C)Cc2cc(C(=O)NS(C)(=O)=O)ccc2NC1c1cccc(N2CC(F)C2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 19.9 %

Procedure:
To a suspension of 60% sodium hydride (165 mg, 4.1 mmol) in N,N-dimethylformamide (1.5 mL) was added methanesulfonamide (400 mg, 4.2 mmol) at room temperature. The resulting mixture was stirred at 25° C. for 1 h. A solution of 2-[3-(3-fluoro-azetidin-1-yl)-phenyl]-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (150 mg, 0.42 mmol), and 1,1′-carbonyldiimidazole (170 mg, 1.04 mmol) in N,N-dimethylformamide (2.0 mL) was stirred at 70° C. After stirring at 70° C. for 1 h, the above suspension of methanesulfonamide and sodium hydride in N,N-dimethylformamide was added and the mixture was allowed to stir at 25° C. for 1 h. Purification by Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) afforded N-{2-[3-(3-fluoro-azetidin-1-yl)-phenyl]-3,3-dimethyl-1,2,3,4-tetrahydro-quinoline-6-carbonyl}-methanesulfonamide (36 mg, 20%) as a white solid: LC/MS m/e calcd for C22H26FN3O3S (M+H)+: 432.51, observed: 432.1.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[CH:10][CH:9]=[CH:8][C:4]=1[C:5]([NH2:7])=[NH:6].Cl.[CH3:13][S:14][C:15]1[N:16]=[N:17][C:18]([C:22](OCC)=[O:23])=[C:19](Cl)[N:20]=1.C(N(CC)CC)C>C(#N)C>[CH3:13][S:14][C:15]1[N:16]=[N:17][C:18]2[C:22](=[O:23])[NH:7][C:5]([C:4]3[CH:8]=[CH:9][CH:10]=[CH:11][C:3]=3[O:2][CH3:1])=[N:6][C:19]=2[N:20]=1
Reactant: COc1ccccc1C(=N)N
Reactant: CCOC(=O)c1nnc(SC)nc1Cl
Agent: Cl
Solvent: CC#N
Solvent: CCN(CC)CC
Product: COc1ccccc1-c1nc2nc(SC)nnc2c(=O)[nH]1
Temperature: 0 °C

Procedure:
A cooled (0° C.) solution of 2-methoxybenzamidine (from 1.97 g of the hydrochloride) in acetonitrile (17 ml) was added to a cooled solution of 3-methylthio-5-chloro-6-carboethoxy-1,2,4-triazine (prepared from 3-methylthio-5-oxo-6-carboethoxy-4,5-dihydro-1,2,4-triazine, 1.08 g, and thionyl chloride, 20 ml) in acetonitrile (17 ml). Triethylamine (0.51 g) was added and the reaction mixture was stirred with cooling (0° C.) for one hour and then at ambient temperature for 17 hours to afford a yellow solid which was washed with acetonitrile and ether to afford the crude title compound (1.39 g). A sample (0.35 g) of this was washed twice with boiling methanol to afford the title compound, 0.25 g, m.p. 267.5-268.5° C. The remaining material (1.04 g) was similarly treated with boiling methanol to afford the title compound, 0.91 g, m.p. 266-268° C.
Reaction SMILES: [ClH:1].[CH3:2][O:3][C@H:4]([CH3:7])[C:5]#[N:6].[CH2:8]([OH:10])[CH3:9]>>[ClH:1].[CH2:8]([O:10][C:5](=[NH:6])[C@H:4]([O:3][CH3:2])[CH3:7])[CH3:9]
Reactant: CCO
Reactant: CO[C@H](C)C#N
Agent: Cl
Product: CCOC(=N)[C@@H](C)OC
Yield: 100 %

Procedure:
Hydrogen chloride gas was passed into an icecold solution of (R)-2-methoxy-propionitrile (prepared according to the method of Example 1, Step A, 9.91 g, 116.5 mmol) in anhydrous ethanol (100 mL) until the solution was saturated with the gas. The reaction was stored in a refrigerator over night. The excess ethanol was removed under vacuum to obtain the title compound of Example 1, Step B as a deliquescent solid (19.5 g, 100% yield); [α]D+46.4 (c=1, methanol); 1H NMR (CDCl3, 300 MHz) δ1.4 (d, 3H), 3.4 (s, 1H), 3.7 (q, 2H), 4.8 (q, 1H), 6.2 (b, 1H).
Reaction SMILES: I.[NH2:2][CH2:3][CH2:4][CH2:5][NH:6][C:7]1[C:8]([C:12]2[N:16]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[C:19]([Br:24])[CH:18]=3)[C:15](=[O:25])[O:14][N:13]=2)=[N:9][O:10][N:11]=1.[S:26](N)([NH2:29])(=[O:28])=[O:27]>N1C=CC=CC=1>[Br:24][C:19]1[CH:18]=[C:17]([N:16]2[C:15](=[O:25])[O:14][N:13]=[C:12]2[C:8]2[C:7]([NH:6][CH2:5][CH2:4][CH2:3][NH:2][S:26]([NH2:29])(=[O:28])=[O:27])=[N:11][O:10][N:9]=2)[CH:22]=[CH:21][C:20]=1[F:23]
Reactant: NS(N)(=O)=O
Reactant: NCCCNc1nonc1-c1noc(=O)n1-c1ccc(F)c(Br)c1
Agent: I
Solvent: c1ccncc1
Product: NS(=O)(=O)NCCCNc1nonc1-c1noc(=O)n1-c1ccc(F)c(Br)c1
Yield: 71.7 %

Procedure:
A solution of 3-{4-[(3-aminopropyl)amino]-1,2,5-oxadiazol-3-yl}-4-(3-bromo-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one hydroiodide (150 mg, 0.28 mmol) and sulfamide (160 mg, 1.7 mmol) in pyridine (2.5 mL) was heated in a microwave at 130° C. for 10 min. The reaction mixture was concentrated to give a crude residue. This material was purified by preparative LCMS to give the desired product (96 mg, 71%) as a solid. LCMS for C13H14BrFN7O5S (M+H)+: m/z=478.0, 480.0. 1H NMR (400 MHz, DMSO-d6): δ 8.07 (dd, J=6.2, 2.5 Hz, 1H), 7.73-7.69 (m, 1H), 7.59 (dd, J=8.8, 8.6 Hz, 1H), 6.57-6.51 (m, 4H), 3.31-3.26 (m, 2H), 2.92-2.87 (m, 2H), 1.79-1.72 (m, 2H).
Reaction SMILES: [CH3:1][C@@:2]([NH:15][NH2:16])([C:12]([OH:14])=[O:13])[CH2:3][C:4]1[CH:5]=[CH:6][C:7]([OH:11])=[C:8]([OH:10])[CH:9]=1.[C:17](Cl)(=O)C>CO>[OH:10][C:8]1[CH:9]=[C:4]([CH2:3][C:2]([NH:15][NH2:16])([CH3:1])[C:12]([O:14][CH3:17])=[O:13])[CH:5]=[CH:6][C:7]=1[OH:11]
Reactant: C[C@@](Cc1ccc(O)c(O)c1)(NN)C(=O)O
Reactant: CC(=O)Cl
Solvent: CO
Product: COC(=O)C(C)(Cc1ccc(O)c(O)c1)NN
Temperature: 65 °C
Reaction time: 4 h
Yield: 99 %

Procedure:
To a solution of carbidopa (226 mg, 1 mmol) in anhydrous methanol (20 mL), was added acetyl chloride (1 mL) at 0° C. The mixture was stirred at 65° C. in a pressure vessel for 4 h. Removal of solvent yielded 270 mg (99%) of the title compound as its hydrochloride salt. 1H NMR (CD3OD, 400 MHz): 1.46 (s, 3H), 2.86 (dd, 2H), 3.78 (s, 3H), 6.45 (dd, J=8 Hz, J=2 Hz), 6.56 (d, J=2.4 Hz), 6.69 (d, J=8.4 Hz). MS (ESI) m/z 241.15 (M+H+).
Reaction SMILES: P(Cl)(Cl)Cl.[Cl:5][C:6]1[CH:7]=[CH:8][C:9]2[N:15]([CH3:16])[C:14](=[O:17])[CH:13]([F:18])[N+:12]([O-])=[C:11]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:10]=2[CH:26]=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[Cl:5][C:6]1[CH:7]=[CH:8][C:9]2[N:15]([CH3:16])[C:14](=[O:17])[CH:13]([F:18])[N:12]=[C:11]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:10]=2[CH:26]=1
Reactant: CN1C(=O)C(F)[N+]([O-])=C(c2ccccc2)c2cc(Cl)ccc21
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: ClP(Cl)Cl
Product: CN1C(=O)C(F)N=C(c2ccccc2)c2cc(Cl)ccc21
Reaction time: 2 h
Yield: 65.1 %

Procedure:
A 580 μl (6.6 mmole) of phosphorous trichloride was added to a solution of 1.05 g (3.3 mmole) of 7-chloro-3-fluoro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide in 15 ml methylene chloride at 5°. The solution was stirred for 2 hr at 5° and then 20 hr at 25°, and then poured into 100 ml of cold aqueous 5% sodium bicarbonate solution. The organic layer was separated, washed with water, dried (MgSO4) and evaporated to dryness to give 800 mg (80%) of crude product. Recrystallization from heptane gave 650 mg (65%) of 7-chloro-3-fluoro-1.3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one as colorless crystals, mp 139°-140°. Even under these mild conditions, an appreciable amount of 3,7-dichloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one is formed as an impurity. If the reaction mixture is heated to 61° C. for only 10 min., none of the desired 3-fluoro compound is formed.
Reaction SMILES: [Cl:1]([O-:5])(=[O:4])(=[O:3])=[O:2].[CH2:6]([C:8]1([CH2:28][CH2:29][C:30]([OH:32])=[O:31])[C:17]2[C:16]3[NH:18][C:19]4[C:24]([C:15]=3[CH2:14][CH:13](C(O)=O)[N+:12]=2[CH2:11][CH2:10][CH2:9]1)=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH3:7].C1C2C(CCCC2)CCC1>>[Cl:1]([O-:5])(=[O:4])(=[O:3])=[O:2].[CH2:6]([C:8]1([CH2:28][CH2:29][C:30]([OH:32])=[O:31])[C:17]2[C:16]3[NH:18][C:19]4[C:24]([C:15]=3[CH2:14][CH2:13][N+:12]=2[CH2:11][CH2:10][CH2:9]1)=[CH:23][CH:22]=[CH:21][CH:20]=4)[CH3:7]
Reactant: CCC1(CCC(=O)O)CCC[N+]2=C1c1[nH]c3ccccc3c1CC2C(=O)O
Agent: [O-][Cl+3]([O-])([O-])[O-]
Solvent: C1CCC2CCCCC2C1
Product: CCC1(CCC(=O)O)CCC[N+]2=C1c1[nH]c3ccccc3c1CC2
Yield: 97.2 %

Procedure:
1000 mg. (2.13 mmoles) of (+)-1α-ethyl-1β- carboxyethyl-6-carboxy-1,2,3,4,6,7-hexahydro-12H-indolo(2,3-a)-quinolizin-5-ium perchlorate in 15 ml. of decalin are heated at 160° to 170° C. for 25 minutes, with stirring. The substance melts accompanied by gas evolution. After cooling the reaction mixture is filtered, the solid obtained is washed decalin-free with three 5-ml. portions of ether and is dried. 880 mg. of the title compound are obtained. Yield: 97.2% [α]D25 =-19°.
Reaction SMILES: [CH2:1]([C:4]([CH:13]([C:28]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=1)[CH2:14][C:15]1[C:20]([C:21]([F:24])([F:23])[F:22])=[CH:19][CH:18]=[CH:17][C:16]=1[N+:25]([O-])=O)([C:9]([O:11][CH3:12])=[O:10])[C:5]([O:7][CH3:8])=[O:6])[CH:2]=[CH2:3].Cl.C(OCC)(=O)C.C(=O)([O-])[O-].[K+].[K+]>CO>[CH2:1]([C:4]([CH:13]([C:28]1[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=1)[CH2:14][C:15]1[C:20]([C:21]([F:22])([F:24])[F:23])=[CH:19][CH:18]=[CH:17][C:16]=1[NH2:25])([C:9]([O:11][CH3:12])=[O:10])[C:5]([O:7][CH3:8])=[O:6])[CH:2]=[CH2:3]
Reactant: C=CCC(C(=O)OC)(C(=O)OC)C(Cc1c([N+](=O)[O-])cccc1C(F)(F)F)c1ccc(OC)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: CCOC(C)=O
Product: C=CCC(C(=O)OC)(C(=O)OC)C(Cc1c(N)cccc1C(F)(F)F)c1ccc(OC)cc1
Yield: 110.5 %

Procedure:
α-(2-Propenyl)-[2-(2-nitro-6-trifluoromethylphenyl)-1-(4-methoxyphenyl)ethyl]propanedioic acid, dimethyl ester (15.42 g; 31.12 mmole) was dissolved in methanol (110 ml) under argon at room temperature. Powdered stannous chloride dihydrate (36.52 g; 161.8 mmol; 5.2 eq.) was added followed by concentrated hydrochloric acid (50 ml) with stirring. After ~1.5 hours, Celite, ethyl acetate, and saturated potassium carbonate solution were added with stirring (the potassium carbonate solution was added portionwise). The suspension was filtered, and the solid rinsed with ethyl acetate (three times). The filtrate was concentrated, and the residue was washed with 10% methanol/water. The washings were concentrated and dried in vacuo giving ~16 g of a yellow oil. The solids (tin salts, Celite, potassium bicarbonate, etc.) that had been filtered from the reaction mixture were triturated in acetone (several times) and suction filtered through a pad of Celite. The acetone filtrate was concentrated, and the remaining residue was partitioned between chloroform and water. The chloroform layer was dried (magnesium sulfate) and concentrated, leaving 9.06 g of the title compound as a solid. The remaining product was assumed to be in the aforementioned ~16 g of yellow oil. The yellow oil was used "as is" in the next step, as was the 9.06 g of solid.
Reaction SMILES: [OH:1][C:2]1C=C2C(C=CN2)=[CH:4][CH:3]=1.C(O[C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[N:20]([C:24]([NH2:26])=[O:25])[CH:19]=[C:18]2[N:27]=[C:28]=[O:29])C=C>>[CH2:2]([O:1][C:23]1[CH:22]=[C:21]2[C:17]([C:18]([N:27]=[C:28]=[O:29])=[CH:19][N:20]2[C:24]([NH2:26])=[O:25])=[CH:16][CH:15]=1)[CH:3]=[CH2:4]
Reactant: C=CCOc1ccc2c(c1)c(N=C=O)cn2C(N)=O
Reactant: Oc1ccc2cc[nH]c2c1
Product: C=CCOc1ccc2c(N=C=O)cn(C(N)=O)c2c1

Procedure:
was prepared from 6-hydroxy-indole using the protocol described for the preparation of 5-allyloxy-3-isocyanato-indole-1-carboxylic acid amide in Scheme A4.
Reaction SMILES: [C:1]([O:5][C:6]([CH:8]1[CH2:12][S:11][CH:10]([CH2:13][CH2:14][O:15]C2CCCCO2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>CO>[C:1]([O:5][C:6]([CH:8]1[CH2:12][S:11][CH:10]([CH2:13][CH2:14][OH:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)C1CSC(CCOC2CCCCO2)C1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CC(C)(C)OC(=O)C1CSC(CCO)C1
Temperature: 25 °C
Reaction time: 3 h
Yield: 95.5 %

Procedure:
To a stirred solution of 4-tert-butoxycarbonyl-2-(2-tetrahydropyranyloxyethyl)tetrahydrothiophene (0.67 g) in methanol (20 ml), p-toluenesulfonic acid monohydrate (40 mg) was added and the mixture was stirred for 3 hours at room temperature. Saturated aqueous sodium bicarbonate solution was added to the mixture and extracted with ethyl acetate. The organic layer was washed with water and saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated in vacuo. The oily residue was purified by a silica gel column chromatography to give 470 mg (96%) of the titled compound (compound No. 2-1).
Reaction SMILES: [Cl:1][C:2]1[C:10]2[N:9]=[N:8][N:7]([CH2:11][CH:12]3[CH2:14][CH2:13]3)[C:6]=2[CH:5]=[CH:4][C:3]=1[OH:15].[Br:16][C:17]1[C:18](Cl)=[N:19][CH:20]=[CH:21][CH:22]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(N(C)C)=O>[Br:16][C:17]1[C:18]([O:15][C:3]2[CH:4]=[CH:5][C:6]3[N:7]([CH2:11][CH:12]4[CH2:14][CH2:13]4)[N:8]=[N:9][C:10]=3[C:2]=2[Cl:1])=[N:19][CH:20]=[CH:21][CH:22]=1
Reactant: Oc1ccc2c(nnn2CC2CC2)c1Cl
Reactant: Clc1ncccc1Br
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC(=O)N(C)C
Product: Clc1c(Oc2ncccc2Br)ccc2c1nnn2CC1CC1
Temperature: 140 °C
Reaction time: 1 h

Procedure:
4-Chloro-1-(cyclopropylmethyl)-1H-benzotriazol-5-ol (8-5, 50 mg, 0.22 mmol, 1 equiv.) was dissolved in dimethylacetamide (1.5 mL) and treated with 3-bromo-2-chloropyridine (50 mg, 0.25 mmol, 1.15 equiv.) and cesium carbonate (146 mg, 0.45 mmol, 2 equiv). The mixture was stirred under microwave irradiation at 140° C. for 1 hour, treated with additional 3-bromo-2-chloropyridine (50 mg, 0.25 mmol, 1.15 equiv.) and cesium carbonate (80 mg, 0.24 mmol, 1 equiv.) and stirred for an additional hour at 140° C. under microwave irradiation. The mixture was extracted from water (50 mL) with ethyl acetate (3×50 mL) and the combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified via silica gel chromatography (100:0 to 50:50; hexanes:ethyl acetate) to provide the titled compound 395 as a white powder.
Reaction SMILES: [CH3:1][C:2]1[C:7]([CH:8]([OH:13])[C:9]([O:11][CH3:12])=[O:10])=[CH:6][CH:5]=[CH:4][N:3]=1.[K+].[Br-].Cl[O-].[Na+]>C(Cl)Cl.O>[CH3:1][C:2]1[C:7]([C:8](=[O:13])[C:9]([O:11][CH3:12])=[O:10])=[CH:6][CH:5]=[CH:4][N:3]=1
Reactant: COC(=O)C(O)c1cccnc1C
Agent: [Br-]
Agent: [K+]
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: COC(=O)C(=O)c1cccnc1C
Temperature: 25 °C
Reaction time: 1 h
Yield: 76.7 %

Procedure:
A stirred mixture of 3 g (16 mmol) of methyl (2-methylpyrid-3-yl)-α-hydroxyacetate (Example 1b) in 20 ml of methylene chloride and 0.5 g (3.5 mmol) of Na2HPO4, 0.6 g (5 mmol) of NaH2PO4 and 0.2 g (1.6 mmol) of KBr in 20 ml of water was treated with a spatula-tipful of tetramethylpyridine N-oxyl and 10 ml of 12.5% strength sodium hypochlorite solution. The mixture was stirred for 1 hour at room temperature, and the organic phase was subsequently separated off and concentrated. The residue obtained was 2.2 g (77%) of the title compound as a yellow oil.
Reaction SMILES: [CH3:1][C@@H:2]1[C@@H:7]([CH2:8][O:9][Si](C(C)(C)C)(C)C)[O:6][C:4](=[O:5])[CH2:3]1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1>[CH3:1][C@@H:2]1[C@@H:7]([CH2:8][OH:9])[O:6][C:4](=[O:5])[CH2:3]1
Reactant: C[C@H]1CC(=O)O[C@@H]1CO[Si](C)(C)C(C)(C)C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: C[C@H]1CC(=O)O[C@@H]1CO

Procedure:
2,3-Dideoxy-3-C-methyl-5-O-tert-butyldimethylsilyl-D-erythro-pentono-1,4-lactone (1.4 g, 6.13 mmol) was treated with tetra-n-butylammonium fluoride (8.7 mL of a 1.0M solution in tetrahydrofuran, 8.7 mmol) for 90 minutes at room temperature. The reaction mixture was evaporated, and the crude product subjected to flash silica gel chromatography eluting initially with 15% acetone in hexane and subsequently with 25% acetone in hexane. Pure title compound was obtained as an oil; yield 710 mg (89%); 1H NMR (400 MHz, CDCl3): δ1.16 (d, 3H), 2.21 (dd, 1H), 2.50 (m, 1H), 2.72 (dd, 1H).
Reaction SMILES: [CH:1]1([CH2:4][NH:5][S:6]([C:9]2[C:14]([Cl:15])=[CH:13][CH:12]=[C:11]([N+:16]([O-:18])=[O:17])[C:10]=2Cl)(=[O:8])=[O:7])[CH2:3][CH2:2]1.[H-].[Na+].[OH2:22]>>[Cl:15][C:14]1[C:9]([S:6]([NH:5][CH2:4][CH:1]2[CH2:3][CH2:2]2)(=[O:8])=[O:7])=[C:10]([OH:22])[C:11]([N+:16]([O-:18])=[O:17])=[CH:12][CH:13]=1
Reactant: O
Reactant: O=[N+]([O-])c1ccc(Cl)c(S(=O)(=O)NCC2CC2)c1Cl
Agent: [H-]
Agent: [Na+]
Product: O=[N+]([O-])c1ccc(Cl)c(S(=O)(=O)NCC2CC2)c1O
Yield: 72.7 %

Procedure:
Following the general hydrolysis procedure outlined in example 15, N-cyclopropylmethyl-2,6 dichloro-3-nitrobenzenesulfonamide (0.85 g, 2.6 mmol), 80% NaH (0.23 g, 9.88 mmol) and water (56 μL, 3.1 mmol) were reacted to form the desired product (0.58 g, 72%). LC-MS m/z 307 M+).
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])=[N:4][C:3]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[Br:18]N1C(=O)CCC1=O.N(C(C)(C)C#N)=NC(C)(C)C#N>C(Cl)(Cl)(Cl)Cl>[Br:18][CH2:1][C:2]1[O:6][C:5]([CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])=[N:4][C:3]=1[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: CCCCCc1nc(-c2ccccc2)c(C)o1
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: ClC(Cl)(Cl)Cl
Product: CCCCCc1nc(-c2ccccc2)c(CBr)o1

Procedure:
5-Methyl-2-pentyl-4-phenyloxazole (4.25 g) was brominated with N-bromosuccinimide (3.4 g) in carbon tetrachloride in the presence of azobisisobutyronitrile (0.2 g). The procedure gave an oil of 5-bromomethyl-2-pentyl-4-phenyloxazole, yield 5.70 g (99.7%).
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3[F:19])[C:12](Br)=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:21]([C:23]1[S:27][C:26](B(O)O)=[CH:25][CH:24]=1)=[O:22].C(N(CC)CC)C>C(O)C.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]1([S:7]([N:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3[F:19])[C:12]([C:26]3[S:27][C:23]([CH:21]=[O:22])=[CH:24][CH:25]=3)=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=S(=O)(c1ccccc1)n1cc(Br)c2cccc(F)c21
Reactant: O=Cc1ccc(B(O)O)s1
Agent: Cl[Pd]Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: CCO
Product: O=Cc1ccc(-c2cn(S(=O)(=O)c3ccccc3)c3c(F)cccc23)s1
Yield: 77.3 %

Procedure:
A solution of 1-benzenesulfonyl-3-bromo-7-fluoroindole (0.5 g, 1.41 mmol), 5-formyl-2-thiophene boronic acid (0.24 g, 1.55 mmol), bis(triphenylphosphine) palladium (II) dichloride (0.06 g, 0.08 mmol) and triethylamine (0.39 ml, 2.82 mmol) in ethanol (4 ml) was subjected to microwave irradiation at 150° C. for 420 s. The resulting suspension was concentrated under reduced pressure and the residue passed through a silica pad eluting with dichloromethane to afford crude 5-(1-benzenesulfonyl-7-fluoroindol-3-yl)-thiophene-2-carboxaldehyde as a brown solid (0.42 g) which was used in the next step with no further purification.
Reaction SMILES: [OH:1][NH:2][C:3]([N:5]1[CH2:10][CH2:9][CH:8]([C@H:11]2[O:29][C:14]3=[CH:15][N:16]=[C:17]([C:19]4[CH2:20][CH2:21][N:22]([S:25]([CH3:28])(=[O:27])=[O:26])[CH2:23][CH:24]=4)[CH:18]=[C:13]3[CH2:12]2)[CH2:7][CH2:6]1)=[NH:4].[CH3:30][C:31]1([C:34](Cl)=O)[CH2:33][CH2:32]1>>[CH3:28][S:25]([N:22]1[CH2:21][CH:20]=[C:19]([C:17]2[CH:18]=[C:13]3[CH2:12][C@@H:11]([CH:8]4[CH2:9][CH2:10][N:5]([C:3]5[N:4]=[C:30]([C:31]6([CH3:34])[CH2:33][CH2:32]6)[O:1][N:2]=5)[CH2:6][CH2:7]4)[O:29][C:14]3=[CH:15][N:16]=2)[CH2:24][CH2:23]1)(=[O:27])=[O:26]
Reactant: CC1(C(=O)Cl)CC1
Reactant: CS(=O)(=O)N1CC=C(c2cc3c(cn2)O[C@H](C2CCN(C(=N)NO)CC2)C3)CC1
Product: CC1(c2nc(N3CCC([C@@H]4Cc5cc(C6=CCN(S(C)(=O)=O)CC6)ncc5O4)CC3)no2)CC1

Procedure:
The title compound is prepared from (S)—N-hydroxy-4-[5-(1-methanesulfonyl-1,2,3,6-tetrahydro-pyridin-4-yl)-2,3-dihydro-furo[2,3-c]pyridin-2-yl]-piperidine-1-carboxamidine (Intermediate 47; the configuration of the stereocenter is arbitrarily assigned) and 1-methyl-cyclopropanecarbonyl chloride following a procedure analogous to that described in Example 8. LC (method 6): tR=1.53 min; Mass spectrum (ESI+): m/z=486 [M+H]+.
Reaction SMILES: [CH:1]1([C:4]2[NH:9][C:8](=[O:10])[CH:7]=[C:6]([C:11]3[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=3)[CH:5]=2)[CH2:3][CH2:2]1.[OH-].[Na+].[NH2:23]OS(O)(=O)=O>C1COCC1.O>[NH2:23][N:9]1[C:4]([CH:1]2[CH2:2][CH2:3]2)=[CH:5][C:6]([C:11]2[CH:12]=[CH:13][C:14]([C:17]([F:20])([F:18])[F:19])=[CH:15][CH:16]=2)=[CH:7][C:8]1=[O:10]
Reactant: O=c1cc(-c2ccc(C(F)(F)F)cc2)cc(C2CC2)[nH]1
Reactant: NOS(=O)(=O)O
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: Nn1c(C2CC2)cc(-c2ccc(C(F)(F)F)cc2)cc1=O
Temperature: 23 °C
Reaction time: 20 h
Yield: 63.7 %

Procedure:
To a solution of 6-cyclopropyl-4-(4-trifluoromethyl-phenyl)-1H-pyridin-2-one (example C.28 step 2) (4.19 g, 15.0 mmol) in THF (225 mL) and 1M NaOH (90.0 mL, 90.0 mmol) was added dropwise a solution of hydroxylamine-O-sulfonic acid (HOSA) (95%, 5.36 g, 45.0 mmol) in H2O (60 mL) at 0° C. The reaction mixture was stirred at 23° C. for 20 h (76% conversion). Added again at 0° C. 3N NaOH (30 mL, 30.0 mmol) and then hydroxylamine-O-sulfonic acid (HOSA) (95%, 5.36 g, 45.0 mmol) and the reaction mixture was stirred at 23° C. for 3 days (88% conversion). Poured into ice water, extracted with EtOAc, washed the organic layers with brine, dried over Na2SO4. Removal of the solvent in vacuum left a residue (5.17 g) which was purified by silica gel chromatography (400 g SiO2) to give the title compound as a light yellow solid (2.81 g, 64%). MS (ISP) 295.5 [(M+H)+]; mp 132° C.