Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C@@H:6]([C:12]1[C:28]([CH3:29])=[CH:27][C:15]2[N:16]=[C:17]([C:19]3[C:24]([CH3:25])=[CH:23][N:22]=[C:21](Cl)[CH:20]=3)[S:18][C:14]=2[C:13]=1[C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].[CH3:37][N:38]1[C:46]2[C:41](=[CH:42][C:43](B(O)O)=[CH:44][CH:45]=2)[CH:40]=[N:39]1.C([O-])([O-])=O.[K+].[K+]>CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C@@H:6]([C:12]1[C:28]([CH3:29])=[CH:27][C:15]2[N:16]=[C:17]([C:19]3[C:24]([CH3:25])=[CH:23][N:22]=[C:21]([C:43]4[CH:42]=[C:41]5[C:46](=[CH:45][CH:44]=4)[N:38]([CH3:37])[N:39]=[CH:40]5)[CH:20]=3)[S:18][C:14]=2[C:13]=1[C:30]1[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][CH:31]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:3])([CH3:4])[CH3:2]
Reactant: Cn1ncc2cc(B(O)O)ccc21
Reactant: CCOC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(-c3cc(Cl)ncc3C)sc2c1-c1ccc(Cl)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Product: CCOC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(-c3cc(-c4ccc5c(cnn5C)c4)ncc3C)sc2c1-c1ccc(Cl)cc1
Temperature: 120 °C

Procedure:
A microwave vial containing (S)-ethyl 2-(tert-butoxy)-2-(2-(2-chloro-5-methylpyridin-4-yl)-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)acetate (68 mg, 0.13 mmol) was charged with (1-methyl-1H-indazol-5-yl)boronic acid (44 mg, 0.25 mmol), then Pd(PPh3)4 (24 mg, 0.02 mmol). The vial was flushed with argon, diluted with dioxane (2.0 mL) and to this was added 2M aqueous K2CO3 (0.20 mL, 0.40 mmol). The vial was sealed, heated to 120° C. for 3 hours, and then allowed to cool to room temperature. The mixture was diluted with EtOAc, dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by silica gel column chromatography (10-45% EtOAc/Hex gradient) to afford the desired product. LCMS-ESI+: calc'd for C36H36ClN4O3S: 639.2 (M+H+); Found: 639.2 (M+H+).
Reaction SMILES: C(O[C:4]1[C:5](=[O:12])[C:6](=[O:11])[C:7]=1[O:8][CH2:9][CH3:10])C.[CH:13]1([NH2:16])[CH2:15][CH2:14]1.C(N(CC)CC)C>CCO>[CH:13]1([NH:16][C:4]2[C:5](=[O:12])[C:6](=[O:11])[C:7]=2[O:8][CH2:9][CH3:10])[CH2:15][CH2:14]1
Reactant: NC1CC1
Reactant: CCOc1c(OCC)c(=O)c1=O
Solvent: CCN(CC)CC
Solvent: CCO
Product: CCOc1c(NC2CC2)c(=O)c1=O
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 20.5 %

Procedure:
To a solution of 3,4-diethoxycyclobut-3-ene-1,2-dione (0.596 g, 3.5 mmol) in EtOH (5 mL) was added cyclopropylamine (0.2 g, 3.5 mmol), followed by triethylamine (0.49 mL, 3.5 mmol). The reaction mixture was stirred at room temperature for 30 minutes. The title compound (0.13 g, 20%) formed as a white precipitate that was collected by filtration and washed with diethyl ether. LCMS (ES+) 182 (M+H)+, RT 1.42 minutes (method 1).
Reaction SMILES: [NH2:1][CH:2]([CH2:5][CH3:6])[CH2:3][OH:4].C(N(CC)CC)C.[Cl:14][CH2:15][C:16](Cl)=[O:17]>ClCCl.CCOC(C)=O>[Cl:14][CH2:15][C:16]([NH:1][CH:2]([CH2:5][CH3:6])[CH2:3][OH:4])=[O:17]
Reactant: CCC(N)CO
Reactant: O=C(Cl)CCl
Solvent: CCOC(C)=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCC(CO)NC(=O)CCl
Temperature: -70 °C
Reaction time: 0.25 h
Yield: 98 %

Procedure:
To a mixture of 2-amino-1-butanol (5.0 mL, 53 mmol) and triethyl amine (15.0 mL, 111 mmol) in dichloromethane (20 mL) at −70° C. was added chloroacetyl chloride (4.6 mL, 58 mmol) dropwise. The reaction mixture was stirred at −70° C. for 15 min. and then was allowed to warm to rt. It was diluted with EtOAc (50 mL) and the reaction was quenched by adding water (50 mL). The organic layer was separated and the aqueous layer was extracted with EtOAc (3×30 mL). The combined organic layers was concentrated to afford 2-(2-chloroacetamido)-1-butanol (8.6 g, 98%) as a brown solid.
Reaction SMILES: [OH-].[Na+].[NH:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]([OH:14])=[O:13])=[CH:4]1.Br[CH2:16][CH:17]1[CH2:19][CH2:18]1>CC(C)=O.O>[CH:17]1([CH2:16][N:3]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]([C:12]([OH:14])=[O:13])=[CH:4]2)[CH2:19][CH2:18]1
Reactant: O=C(O)c1c[nH]c2ccccc12
Reactant: BrCC1CC1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(C)=O
Product: O=C(O)c1cn(CC2CC2)c2ccccc12
Temperature: 25 °C
Reaction time: 24 h

Procedure:
Powdered sodium hydroxide (10 g) was added cautiously to a stirred solution of indole-3-carboxylic acid (5 g) and (bromomethyl)cyclopropane (10 g) in dry acetone (50 ml). The mixture was stirred for 24 hours at room temperature then diluted with water (250 ml) and washed with dichloromethane (2×100 ml). The aqueous phase acidified to pH 2 and the precipitate isolated and dried (6.3 g), m.p. 157° C.; δH (360 MHz, CDCl3) 0.02-0.04 (2H, m, CH2), 0.18-0.28 (2H, m, CH2), 0.83-0.89 (1H, m, CH), 3.57 (2H, d, J=7 Hz, NCH2), 6.7-6.8 (2H, m, H-5, H-6), 6.9 (1H, d, J=7 Hz, H-7), 7.55 (1H, s, H-2), 7.72 (1H, d, J=7 Hz, H- 4); m/z 215 (M+, 100%), 174 (60), 144 (40).
Reaction SMILES: [C:1]([O:4][CH2:5][C:6]1[CH:10]=[CH:9][O:8][C:7]=1[C:11](=[O:13])[CH3:12])(=[O:3])[CH3:2].[Br-:14].[Br-].[Br-].[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1.C(=O)(O)[O-].[Na+]>C(O)(=O)C>[C:1]([O:4][CH2:5][C:6]1[CH:10]=[CH:9][O:8][C:7]=1[C:11](=[O:13])[CH2:12][Br:14])(=[O:3])[CH3:2]
Reactant: [Br-]
Reactant: CC(=O)OCc1ccoc1C(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Agent: c1cc[nH+]cc1
Solvent: CC(=O)O
Product: CC(=O)OCc1ccoc1C(=O)CBr
Temperature: 25 °C
Reaction time: 3 h
Yield: 95 %

Procedure:
3-Acetoxymethyl-2-acetylfuran (1.7 g, 9.3 mmol, prepared according to the procedure described in Acta. Chemica. Scandinavia, 1990, 44, 916) was dissolved in acetic acid (30 ml). To the solution was added pyridinium tribromide (3.3 g, 10.2 mmol) and the resulting mixture was stirred at room temperature for 3 h. The mixture was cooled to 0° C. and saturated aqueous sodium bicarbonate added dropwise until the solution was basic. The mixture was extracted with ethyl acetate (100 ml). The organic extract was washed with brine (100 ml), dried (MgSO4) and concentrated to give 2.3 g (95%) of the title compound. 1H-NMR (CDCl3) δ: 7.54 (1 H, d, J=1.6 Hz), 6.65 (1 H, d, J=1.6 Hz), 5.38 (2 H, s), 4.37 (2 H, s), 2.09 (3 H, s).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]([NH:10][CH2:11][C:12]2[N:13](COCC[Si](C)(C)C)[CH:14]=[CH:15][N:16]=2)=[O:9])[CH:5]=[C:4]([C:25]2[O:26][CH:27]=[CH:28][CH:29]=2)[N:3]=1.Cl>CO>[NH2:1][C:2]1[N:7]=[C:6]([C:8]([NH:10][CH2:11][C:12]2[NH:13][CH:14]=[CH:15][N:16]=2)=[O:9])[CH:5]=[C:4]([C:25]2[O:26][CH:27]=[CH:28][CH:29]=2)[N:3]=1
Reactant: C[Si](C)(C)CCOCn1ccnc1CNC(=O)c1cc(-c2ccco2)nc(N)n1
Agent: Cl
Solvent: CO
Product: Nc1nc(C(=O)NCc2ncc[nH]2)cc(-c2ccco2)n1
Temperature: 80 °C
Reaction time: 1 h
Yield: 70.8 %

Procedure:
A solution of 2-amino-6-(2-furyl)-N-(1-(2-(trimethylsilyl)ethoxy)methyl-1H-imidazol-2-ylmethyl)pyrimidine-4-carboxamide (340 mg, 0.82 mmol) in MeOH (20 mL) at 0° C. was treated dropwise with conc HCl (4 mL), stirred at 80° C. for 1 h, cooled to room temperature and concentrated in vacuo. The residue was triturated with diethyl ether and the resulting dihydrochloride salt (230 mg, 78%) filtered, washed with diethyl ether, stirred with saturated aqueous NaHCO3 (5 mL), filtered and washed with water to give the title compound (165 mg, 71%) as a yellow solid.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[C:5]([CH3:11])=[CH:4][C:3]=1[C@H:12]1[CH2:16][O:15][C:14](=[O:17])[NH:13]1>CO.[Pd]>[NH2:8][C:6]1[C:5]([CH3:11])=[CH:4][C:3]([C@H:12]2[CH2:16][O:15][C:14](=[O:17])[NH:13]2)=[C:2]([CH3:1])[CH:7]=1
Reactant: Cc1cc([N+](=O)[O-])c(C)cc1[C@H]1COC(=O)N1
Agent: [Pd]
Solvent: CO
Product: Cc1cc([C@H]2COC(=O)N2)c(C)cc1N
Temperature: 25 °C
Reaction time: 14 h

Procedure:
To a solution of (S)-4-(2,5-dimethyl-4-nitrophenyl)oxazolidin-2-one (55 mg, 0.23 mmol) in MeOH (5 mL) was added Pd/C (5 mg, 10% w/w). The mixture was degassed and stirred at room temperature under 1 atm. H2 for 14 h. The Pd/C was removed by filtering through Celite. The filtrate was concentrated to provide (S)-4-(4-amino-2,5-dimethylphenyl)-oxazolidin-2-one which was used in the next step without further purification; ESMS m/z 207.1 (M+H+).
Reaction SMILES: [CH3:1]I.[Mg].[CH3:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12](=[O:16])[C:13]([OH:15])=[O:14])=[CH:8][CH:7]=1.O>C(OCC)C.O1CCCC1>[OH:16][C:12]([C:9]1[CH:8]=[CH:7][C:6]([O:5][CH3:4])=[CH:11][CH:10]=1)([CH3:1])[C:13]([OH:15])=[O:14]
Reactant: CI
Reactant: COc1ccc(C(=O)C(=O)O)cc1
Agent: [Mg]
Solvent: C1CCOC1
Solvent: CCOCC
Solvent: O
Product: COc1ccc(C(C)(O)C(=O)O)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 92.9 %

Procedure:
Methyl iodide (55 ml, 880 mmol) was slowly added to a solution of magnesium (23 g) in diethyl ether (500 ml) at -20° C. and then stirred for 3 hours at room temperature. To the resulting suspension was slowly added dropwise 4-methoxyphenylglyoxylic acid (34.6 g, 192 mmol), as prepared in Example 21, dissolved in dry tetrahydrofuran (100 ml) at 0° C., and the reaction mixture was stirred for about 12 hours at room temperature. After adding cooling water, the reaction solution was extracted with ethyl acetate and the organic layer was washed with water and saturated sodium thiosulfate solution and dried over anhydrous magnesium sulfate. The residue was concentrated under reduced pressure to remove the organic solvent to obtain 35 g (yield: 93%) of the title compound as a yellow solid.
Reaction SMILES: C(OC([NH:11][CH:12]1[N:18]=[C:17]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[F:25])[C:16]2[CH:26]=[CH:27][CH:28]=[C:29]([CH3:30])[C:15]=2[N:14]([CH2:31][C:32]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[N+:40]([O-:42])=[O:41])=[O:33])[C:13]1=[O:43])=O)C1C=CC=CC=1.[BrH:44].O>C(O)(=O)C>[BrH:44].[NH2:11][CH:12]1[N:18]=[C:17]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[F:25])[C:16]2[CH:26]=[CH:27][CH:28]=[C:29]([CH3:30])[C:15]=2[N:14]([CH2:31][C:32]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=2[N+:40]([O-:42])=[O:41])=[O:33])[C:13]1=[O:43]
Reactant: Cc1cccc2c1N(CC(=O)c1ccccc1[N+](=O)[O-])C(=O)C(NC(=O)OCc1ccccc1)N=C2c1ccccc1F
Agent: Br
Solvent: O
Solvent: CC(=O)O
Product: Cc1cccc2c1N(CC(=O)c1ccccc1[N+](=O)[O-])C(=O)C(N)N=C2c1ccccc1F
Temperature: 25 °C
Reaction time: 4.5 h
Yield: 81.8 %

Procedure:
A mixture of (3RS)-3-benzyloxycarbonylamino-2,3-dihydro-5-(2-fluorophenyl)-9-methyl-1-(2-nitrophenacyl)-1H-1,4-benzodiazepin-2-one (300 mg)and 30% hydrobromic acid in acetic acid (3 ml) was stirred at room temperature for 4.5 hours. Water and ice were added to the reaction mixture to afford powder, which was collected by filtration, and washed with water to give (3RS)-3-amino-2,3-dihydro-5-(2-fluorophenyl)-9-methyl-1-(2-nitrophenacyl)-1H-1,4-benzodiazepin-2-one hydrobromide (227 mg, 81.8%).
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][C:11]2=[N:14][N:15]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:16]([OH:17])=[C:10]2[CH2:9]1)=O)(C)(C)C.C(C(O)=O)(F)(F)F>C(Cl)Cl>[OH:17][C:16]1[N:15]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])[N:14]=[C:11]2[CH2:12][CH2:13][NH:8][CH2:9][C:10]=12
Reactant: CCOC(=O)Cn1nc2c(c1O)CN(C(=O)OC(C)(C)C)CC2
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CCOC(=O)Cn1nc2c(c1O)CNCC2
Temperature: 25 °C
Reaction time: 2 h

Procedure:
In 50 ml of methylene chloride was dissolved 2.73 g (8.40 mmol) of ethyl 5-t-butoxycarbonyl-3-hydroxy-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-2-acetate, and under ice-cooling, 10 ml of CF3CO2H was added to the solution and the mixture was stirred at room temperature for 2 hours.
Reaction SMILES: [CH:1]1([CH3:13])[CH2:6][CH2:5][CH:4]([CH:7]([CH3:9])[CH3:8])[CH:3]([C:10](Cl)=[O:11])[CH2:2]1.[CH2:14]([CH2:16][NH2:17])[OH:15]>C(Cl)(Cl)Cl>[OH:15][CH2:14][CH2:16][NH:17][C:10]([CH:3]1[CH:4]([CH:7]([CH3:9])[CH3:8])[CH2:5][CH2:6][CH:1]([CH3:13])[CH2:2]1)=[O:11]
Reactant: NCCO
Reactant: CC1CCC(C(C)C)C(C(=O)Cl)C1
Solvent: ClC(Cl)Cl
Product: CC1CCC(C(C)C)C(C(=O)NCCO)C1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of p-menth-3-oyl chloride prepared as in Example 1 (4.0 g., 0.020 moles) in chloroform (30 ml.) was added dropwise to a stirred solution of ethanolamine (3 g., 0.043 moles) in chloroform (50 ml.). The reaction mixture becomes warm, goes cloudy and finally a yellow oil starts to separate out. After stirring for 2 hours at room temperature the mixture was poured into water. The organic layer was separated, washed with dilute H2SO4, and dried (MgSO4). Removal of the solvent left a viscous oil (3.8 g.). This was distilled under vacuum to yield N-(2-hydroxyethyl)-p-menthane-3-carboxamide as a colourless very viscous oil, b.p. 160°/01. mm.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][O:4][CH:3]([CH:7]([C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)[OH:8])[CH2:2]1.BrC1C=CC=CN=1.[F:22][C:23]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:24]=1O>>[F:22][C:23]1[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:24]=1[O:8][C@@H:7]([C:9]1[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=1)[C@@H:3]1[O:4][CH2:5][CH2:6][NH:1][CH2:2]1
Reactant: OC(c1cccnc1)C1CNCCO1
Reactant: Oc1ccc(F)cc1F
Agent: Brc1ccccn1
Product: Fc1ccc(O[C@@H](c2cccnc2)[C@H]2CNCCO2)c(F)c1

Procedure:
(R)-2-[(S)-(2-,4-Difluoro-phenoxy)-pyridin-3-yl-methyl]-morpholine was synthesized via morpholin-2-yl-pyridin-3-yl-methanol from 2-bromopyridine and 2,4-difluorophenol according to general procedure C and was isolated as a gummy oil. MS (APCI): 307 [M+H]+.
Reaction SMILES: [C@H:1]12[CH2:6][C@H:5]1[CH2:4][NH:3][C@@H:2]2[CH2:7][NH:8][C:9]([C:11]1[N:18]2[C:14]([S:15][CH:16]=[CH:17]2)=[N:13][C:12]=1[CH3:19])=[O:10].[Br:20][C:21]1[CH:25]=[CH:24][S:23][C:22]=1[C:26](O)=[O:27]>>[Br:20][C:21]1[CH:25]=[CH:24][S:23][C:22]=1[C:26]([N:3]1[CH2:4][C@H:5]2[C@H:1]([CH2:6]2)[C@H:2]1[CH2:7][NH:8][C:9]([C:11]1[N:18]2[C:14]([S:15][CH:16]=[CH:17]2)=[N:13][C:12]=1[CH3:19])=[O:10])=[O:27]
Reactant: Cc1nc2sccn2c1C(=O)NC[C@H]1NC[C@@H]2C[C@@H]21
Reactant: O=C(O)c1sccc1Br
Product: Cc1nc2sccn2c1C(=O)NC[C@@H]1[C@H]2C[C@H]2CN1C(=O)c1sccc1Br

Procedure:
prepared by reaction of 6-Methyl-imidazo[2,1-b]thiazole-5-carboxylic acid [(1S,2S,5R)-1-(3-aza-bicyclo[3.1.0]hex-2-yl)methyl]-amide with 3-Bromo-thiophene-2-carboxylic acid. LC-MS (basic): tR=1.22 min; [M+H]+=465.0.
Reaction SMILES: C[O:2][C:3]1[CH:22]=[CH:21][C:6]([O:7][C:8]2[CH:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]3[S:16][CH:17]=[C:18]([CH3:20])[N:19]=3)[CH:9]=2)=[CH:5][CH:4]=1.BrB(Br)Br.CC(=CC)C.C([O-])(O)=O.[Na+]>O.ClCCl>[CH3:20][C:18]1[N:19]=[C:15]([NH:14][C:10]2[CH:9]=[C:8]([O:7][C:6]3[CH:21]=[CH:22][C:3]([OH:2])=[CH:4][CH:5]=3)[CH:13]=[CH:12][N:11]=2)[S:16][CH:17]=1
Reactant: COc1ccc(Oc2ccnc(Nc3nc(C)cs3)c2)cc1
Agent: BrB(Br)Br
Agent: CC=C(C)C
Agent: O=C([O-])O
Solvent: O
Solvent: ClCCl
Product: Cc1csc(Nc2cc(Oc3ccc(O)cc3)ccn2)n1
Temperature: 0 °C
Reaction time: 1 h
Yield: 36.7 %

Procedure:
A 50 mL round bottom flask was charged with 4-(4-methoxyphenoxy)-N-(4-methylthiazol-2-yl)pyridin-2-amine (0.20 g, 0.638 mmol) and dichloromethane (6 mL). The solution was cooled to 0° C., and tribromoborane (0.181 mL, 1.91 mmol) and 1 mL of 2-methyl-2-butene were added. The reaction mixture was stirred at 0° C. for 1 hour. Water and saturated solution of NaHCO3 were added, and the reaction mixture was extracted with EtOAc. The organic layer was dried over magnesium sulfate, filtered and concentrated. The residue was purified on a prepacked silica gel column eluting with 20-35% EtOAc in hexanes to give 4-(2-(4-methylthiazol-2-ylamino)pyridin-4-yloxy)phenol (0.07 g, 36.3% yield) as light orange solid. 1H NMR (DMSO) δ 10.91 (s, 1H), 9.51 (s, 1H), 8.11 (dd, 1H), 6.99 (m, 2H), 6.83 (m, 2H), 6.50 (d, 1H), 6.46 (m, 2H), 2.19 (d, 3H); Mass spectrum (esi) m/z=300 (100) (M+H).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([CH2:8][C:9]([C:11]2[CH:12]=[C:13]([NH:17][C:18](=[O:23])[O:19][CH2:20][CH:21]=[CH2:22])[CH:14]=[CH:15][CH:16]=2)=[O:10])[CH:5]=[CH:4][N:3]=1.[F:24]C1C=CC(NC(OCC=C)=O)=CC=1C(OC)=O.ClC1N=C(C)C=CN=1>>[Cl:1][C:2]1[N:7]=[C:6]([CH2:8][C:9]([C:11]2[CH:12]=[C:13]([NH:17][C:18](=[O:23])[O:19][CH2:20][CH:21]=[CH2:22])[CH:14]=[CH:15][C:16]=2[F:24])=[O:10])[CH:5]=[CH:4][N:3]=1
Reactant: C=CCOC(=O)Nc1cccc(C(=O)Cc2ccnc(Cl)n2)c1
Reactant: C=CCOC(=O)Nc1ccc(F)c(C(=O)OC)c1
Agent: Cc1ccnc(Cl)n1
Product: C=CCOC(=O)Nc1ccc(F)c(C(=O)Cc2ccnc(Cl)n2)c1
Yield: 69.9 %

Procedure:
Using multiple iterations of a procedure analogous to the procedure described in Intermediate 11 using methyl 2-fluoro-5-{[(2-propen-1-yloxy)carbonyl]amino}benzoate (104 g, 411 mmol) and 2-chloro-4-methylpyrimidine (59 g, 493 mmol), the title compound of Step B was obtained (100 g, 69.9% yield). 1H NMR (400 MHz, CDCl3) δ ppm 13.67-13.75 (br, 1H), 8.50-8.53 (m, 0.3H), 8.31-8.38 (m, 1H), 7.50-7.82 (m, 2.6H), 6.56-7.20 (m, 3.5H), 6.20-6.25 (m, 1H), 5.82-6.01 (1.3H), 5.20-5.40 (m, 2.6H), 4.50-4.61 (m, 2.6H), 4.31-4.41 (m, 0.9H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH2:11])(=[O:10])=[O:9])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[Cl:18][C:19]1[C:28](Cl)=[N:27][C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[N:20]=1.N#N>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([NH:11][C:28]2[C:19]([Cl:18])=[N:20][C:21]3[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=3)[N:27]=2)(=[O:9])=[O:10])=[CH:6][CH:7]=1
Reactant: Clc1nc2ccccc2nc1Cl
Reactant: NS(=O)(=O)c1ccc(Cl)cc1
Agent: N#N
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=S(=O)(Nc1nc2ccccc2nc1Cl)c1ccc(Cl)cc1
Reaction time: 0.17 h

Procedure:
To a solution of 4-Chlorobenzenesulfonamide (1.92 g, 10 mmol) in anhydrous DMF (50 mL) was added solid potassium carbonate (1.38 g, 10 mmol) in one portion. The reaction mixture was stirred for 10 minutes, followed by the addition of 2,3-dichloroquinoxaline (1.99 g, 10 mmol). Heating the resultant mixture under refux conditions in an atmosphere of N2 for 2.5 h gave the desired product. The progress of the reaction was monitored by TLC using, hexanes/EtOAc 3:1. After cooling the reaction mixture is slowly added to a vigorously stirred aqueous solution of AcOH (1%, 500 mL). The desired product precipitates as grey crystals, which are filtered and dried overnight in desiccator. Yield 2.32 g, 66%; Rf=0.7 (hexanes/EtOAc 1:1); HPLC/MS: [M+H]+ m/z 354. 1H NMR: (DMSO-d6, 600 MHz) 7.68 (t, J=7.8 Hz, 1H), 7.72 (d, J=8.4 Hz, 2H), 7.78 (td, J=7.8 Hz, J=1.2 Hz, 1H), 7.89 (d, J=8.4 Hz, 2H), 8.19 (d, J=8.4 Hz, 2H).
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].[N:7]([CH2:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[N:16]([CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][O:21]1)[N:15]=[CH:14]2)=[N+]=[N-].[OH-].[Na+].C(OCC)(=O)C>C1COCC1>[NH2:7][CH2:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[N:16]([CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][O:21]1)[N:15]=[CH:14]2
Reactant: [N-]=[N+]=NCc1ccc2c(cnn2C2CCCCO2)c1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: NCc1ccc2c(cnn2C2CCCCO2)c1
Temperature: 0 °C
Reaction time: 1 h
Yield: 91.6 %

Procedure:
A solution of LiAlH4 (Aldrich, 10.5 mL, 10.5 mmol, 1.0 M) in THF was added dropwise into a yellow solution of 5-(azidomethyl)-1-(2-tetrahydropyranyl)indazole (compound 109, 2.6 g, 10.1 mmol) in THF (30 mL) at 0° C. After stirring at 0° C. for 1 hour, NaOH (1.0M, 1.5 mL) was added. The reaction mixture was allowed to warm to room temperature. Ethyl acetate (100 mL) was added, and the suspension was filtered (Celite). The filter cake was washed with an addition portion of ethyl acetate (40 mL). Combined organic layers were evaporated under vacuum to give free amine 110 (2.14 g, 92%). MS (electrospray) 232.5 (M+1); 1H NMR (CDCl3) δ 1.61 (m, 3H), 2.02 (m, 2H), 2.50 (m, 1H), 2.83 (br s, 2H), 3.68 (m, 1H), 3.85 (s, 2H), 3.95 (m, 1H), 5.62 (d, 1H, J=9.2 Hz), 7.29 (d, 1H, J=8.8 Hz), 7.48 (d, 1H, J=8.8 Hz), 7.53 (s, 1H), 7.92 (s, 1H).
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[N:11][NH:12][CH:13]=2)[O:3]1.[CH3:15][C@H:16]1[CH2:18][O:17]1.C(N(CC)CC)C>C(#N)C>[CH3:1][C:2]1([CH3:14])[C:6]([CH3:7])([CH3:8])[O:5][B:4]([C:9]2[CH:13]=[N:12][N:11]([CH2:15][C@@H:16]([OH:17])[CH3:18])[CH:10]=2)[O:3]1
Reactant: CC1(C)OB(c2cn[nH]c2)OC1(C)C
Reactant: C[C@H]1CO1
Solvent: CC#N
Solvent: CCN(CC)CC
Product: C[C@H](O)Cn1cc(B2OC(C)(C)C(C)(C)O2)cn1
Yield: 92.5 %

Procedure:
A mixture of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (300 mg, 1.5 mmol)(Aldrich Cat. No. 525057), (S)-(−)-methyloxirane (130 μL, 1.9 mmol) and triethylamine (0.45 mL, 3.2 mmol) in acetonitrile (1.0 mL) in a reaction vial was stirred at 50° C. for 2 h. After cooling it was concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0-50%) to afford the desired product (0.35 g). LCMS (M+H)+=253.0.
Reaction SMILES: [CH3:1][C:2]1[S:3][C:4]([C:7]2[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=2)=[N:5][N:6]=1.[CH3:13][N:14]1[C:18]([N+:19]([O-:21])=[O:20])=[CH:17][N:16]=[C:15]1[CH:22]=O>C(O)(=O)C.C(OC(=O)C)(=O)C.[Cl-].[Cl-].[Zn+2]>[N:10]1[CH:11]=[CH:12][C:7]([C:4]2[S:3][C:2]([CH:1]=[CH:22][C:15]3[N:14]([CH3:13])[C:18]([N+:19]([O-:21])=[O:20])=[CH:17][N:16]=3)=[N:6][N:5]=2)=[CH:8][CH:9]=1
Reactant: Cc1nnc(-c2ccncc2)s1
Reactant: Cn1c([N+](=O)[O-])cnc1C=O
Agent: [Cl-]
Agent: [Zn+2]
Solvent: CC(=O)O
Solvent: CC(=O)OC(C)=O
Product: Cn1c([N+](=O)[O-])cnc1C=Cc1nnc(-c2ccncc2)s1

Procedure:
8.8 g of 2-methyl-5-(4-pyridyl)-1,3,4-thiadiazole and 7.7 g of 1-methyl-5-nitroimidazole-2-carboxaldehyde are heated with 0.2 g of ZnCl2 in a mixture of 50 ml of glacial acetic acid and 25 ml of acetic anhydride for 6 hours at reflux temperature. After cooling, the precipitated solid is suction filtered, washed with concentrated ammonia and recrystallized from dimethylformamide. The melting point of the product obtained is 240°-241° C.
Reaction SMILES: F[C:2]1[C:10]([N+:11]([O-:13])=[O:12])=[CH:9][CH:8]=[C:7]2[C:3]=1/[C:4](=[CH:15]/[C:16]1[NH:17][CH:18]=[CH:19][C:20]=1[O:21][CH3:22])/[C:5](=[O:14])[NH:6]2.C(N(C(C)C)CC)(C)C.C[Si]([N:36]=[N+:37]=[N-:38])(C)C.Cl>C1COCC1.C(O)C>[N:36]([C:2]1[C:10]([N+:11]([O-:13])=[O:12])=[CH:9][CH:8]=[C:7]2[C:3]=1/[C:4](=[CH:15]/[C:16]1[NH:17][CH:18]=[CH:19][C:20]=1[O:21][CH3:22])/[C:5](=[O:14])[NH:6]2)=[N+:37]=[N-:38]
Reactant: C[Si](C)(C)N=[N+]=[N-]
Reactant: COc1cc[nH]c1/C=C1\C(=O)Nc2ccc([N+](=O)[O-])c(F)c21
Agent: Cl
Solvent: CCO
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: COc1cc[nH]c1/C=C1\C(=O)Nc2ccc([N+](=O)[O-])c(N=[N+]=[N-])c21

Procedure:
(Z)-1,3-Dihydro-4-fluoro-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-5-nitro-2H-indol-2-one (6.60 g, 21.8 mmol)(from Example 13) was suspended in 330 mL of THF and 165 mL of ethanol. To this mixture was added diisopropylethylamine (56.9 ml, 326 mmol) and trimethylsilyl azide (28.6 mL, 218 mmol)(Aldrich). The reaction mixture was heated at reflux overnight, and then poured into 2 L mixture of ice and 1N HCl solution. The solid precipitate was filtered, washed with water and dried at 50° C. under high vacuum to give (Z)-4-azido-1,3-dihydro-3-[(3-methoxy-1H-pyrrol-2-yl)methylene]-5-nitro-2H-indol-2-one as a dark red solid. (Yield 6.44 g, 90%).