Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=C[C:5](O)=[C:6]([C:8]2[CH:17]=[CH:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:18]4[N:22]([CH:23]5[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]5)[C:21]5[CH:29]=[CH:30][C:31]([C:33]([OH:35])=[O:34])=[CH:32][C:20]=5[N:19]=4)[CH:14]=3)[N:9]=2)[CH:7]=1.[N:37]1C=CC=C(C(=O)C)C=1.[OH-].[K+]>C(O)C>[CH:23]1([N:22]2[C:21]3[CH:29]=[CH:30][C:31]([C:33]([OH:35])=[O:34])=[CH:32][C:20]=3[N:19]=[C:18]2[C:13]2[CH:14]=[C:15]3[C:10](=[CH:11][CH:12]=2)[N:9]=[C:8]([C:6]2[CH:5]=[N:37][CH:3]=[CH:2][CH:7]=2)[CH:17]=[CH:16]3)[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1
Reactant: CC(=O)c1cccnc1
Reactant: O=C(O)c1ccc2c(c1)nc(-c1ccc3nc(-c4cc(Br)ccc4O)ccc3c1)n2C1CCCCC1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)c1ccc2c(c1)nc(-c1ccc3nc(-c4cccnc4)ccc3c1)n2C1CCCCC1
Yield: 17 %

Procedure:
Following the procedure and workup for Compound 354, Compound 354e (100 mg, 0.256 mmol) was reacted with 1-pyridin-3-yl-ethanone (0.256 mmol) in ethanol (2 mL) using 10% w/v KOH in ethanol (506 μL, 0.64 mmol) to produce the title compound (19 mg, 17% yield). MS: 449.21 (M+H+) HPLC Procedure A, retention time=7.96 min.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10](=[O:28])[CH2:11][CH2:12][C:13]([O:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])=[O:14])=[CH:6][CH:5]=1)([O-])=O>C(OCC)(=O)C.[Pd]>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([C:10](=[O:28])[CH2:11][CH2:12][C:13]([O:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])=[O:14])=[CH:8][CH:9]=1
Reactant: CCCCCCCCCCCCOC(=O)CCC(=O)c1ccc([N+](=O)[O-])cc1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CCCCCCCCCCCCOC(=O)CCC(=O)c1ccc(N)cc1
Yield: 95.6 %

Procedure:
A solution of dodecyl 4-(4-nitrophenyl)-4-oxobutyrate (0.42 g, 1.1 mmol), in ethyl acetate (50 ml) and 10% palladium on carbon (0.10 g) were shaken under hydrogen (30-40 psi) for 10 minutes. The mixture was filtered and the filtrate concentrated in vacuo to give dodecyl 4-(4-aminophenyl)-4-oxobutyrate (0.38 g) as a white solid. 1H NMR (DMSO-d6, 300 MHz) δ: 0.86 (t, J=6.5 Hz, 3H, ester CH3), 1.10-1.37 (m, 18H, ester CH2 's), 1.47-1.60 (m, 2H, ester CH2), 2.57 (t, J=6.5 Hz, 2H, CH2), 3.10 (t, J=6.5 Hz, 2H, CH2), 3.98 (t, J=6.5 Hz, 2H, ester CH2), 6.04 (br s, 2H, NH2), 6.56 (d, J=8.5 Hz, 2H, Ar), 7.68 (d, J=8.5 Hz, 2H, Ar). Anal. Calculated for C22H35NO3.1/20 H2O: C, 72.91; H, 9.76; N, 3.86. Found: C, 72.86; H, 9.83; N, 3.82.
Reaction SMILES: [C:1]1([C:7]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:8][C:9]#[N:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl-].[Al+3].[Cl-].[Cl-].[AlH4-].[Li+]>C1COCC1>[C:11]1([C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[CH:8][CH2:9][NH2:10])[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: N#CC=C(c1ccccc1)c1ccccc1
Agent: [Al+3]
Agent: [AlH4-]
Agent: [Cl-]
Solvent: C1CCOC1
Product: NCC=C(c1ccccc1)c1ccccc1
Temperature: 40 °C
Reaction time: 1 h

Procedure:
To a solution of 3,3-diphenylacrylonitrile (4.45 g, 21.7 mmol) in THF (75 mL) at 0° C. was added aluminum(III) chloride (3.27 g, 24.5 mmol) and lithium tetrahydroaluminate (1 M in THF) (0.910 g, 24.0 mmol) (24 mL). The reaction mixture was warmed to room temperatrue and stirred for 1 h, heated to 40° C. for 2 h, heated to 60° C. for 2 h, quenched with water (5 mL), adjusted to pH 12 with ammonium hydroxide, diluted with brine, and EtOAc, extracted with EtOAc (5×), combined organic extracts washed with brine (1×), dried over MgSO4, filtered, and concentrated. Purification by flash column chromatography on silica gel (eluted with 3% to 10% MeOH (2 M NH3) in DCM) gave 3,3-diphenyl-2-propenylamine.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=1)[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C[N:24]1CCOCC1.ClC(OCC(C)C)=O.N>CN(C=O)C>[NH2:24][C:10](=[O:11])[C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=1
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccc([N+](=O)[O-])cc1)C(=O)O
Reactant: CN1CCOCC1
Agent: CC(C)COC(=O)Cl
Agent: N
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N[C@@H](Cc1ccc([N+](=O)[O-])cc1)C(N)=O
Reaction time: 0.5 h
Yield: 74 %

Procedure:
To a 0° C. solution of 2-(S)-tert-butoxycarbonylamino-3-(4-nitrophenyl)-propionic acid and N-methylmorpholine (1.1 mL, 9.65 mmol) in DMF (10 mL) is added dropwise iso-butyl chloroformate (1.25 mL, 9.65 mmol). The mixture is stirred at 0° C. for 20 minutes after which NH3 (g) is passed through the reaction mixture for 30 minutes at 0° C. The reaction mixture is concentrated and the residue dissolved in EtOAc, washed successively with 5% citric acid, water, 5% NaHCO3, water and brine, dried (Na2SO4), filtered and concentrated in vacuo to a residue that is triturated with a mixture of EtOAc/petroleum ether to provide 2.2 g (74% yield) of the desired product as a white solid.
Reaction SMILES: Cl[C:2]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:3].[Cl:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[CH:18]1[S:32][C:25]2([CH2:30][CH2:29][N:28](C)[CH2:27][CH2:26]2)[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]1=2>ClCCl>[Cl:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[CH:18]1[S:32][C:25]2([CH2:26][CH2:27][N:28]([C:2]([O:4][C:5]3[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=3)=[O:3])[CH2:29][CH2:30]2)[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]1=2
Reactant: CN1CCC2(CC1)SC(c1ccccc1Cl)c1ccccc12
Reactant: O=C(Cl)Oc1ccccc1
Solvent: ClCCl
Product: O=C(Oc1ccccc1)N1CCC2(CC1)SC(c1ccccc1Cl)c1ccccc12
Temperature: 25 °C
Reaction time: 64 h

Procedure:
To 3.83 g of phenyl chloroformate in 850 ml of dichloromethane is added a solution of 6.73 g of the free base 3-(2-chlorophenyl)-1,3-dihydro-1'-methylspiro[benzo(c)thiophene-1,4'-piperidine] of Example 32 in 75 ml of dichloromethane over two minutes. The reaction is stirred at ambient temperature for 64 hours, then diluted with 200 ml of dichloromethane and washed with two 300 ml portions of 5% aqueous sodium hydroxide solution, two 200 ml portions of water and one 75 ml portion of brine. The solution is dried over magnesium sulfate and evaporated to an oil. The oil is chromatographed on a silca gel with dichloromethane to give an oil of 3-(-2-chlorophenyl)-1,3-dihydro-1'-phenoxy carbonylspiro[benzo(c)thiophene-1,4'-piperidine].
Reaction SMILES: [F:1][C:2]([F:19])([F:18])[C:3]1[CH:8]=[CH:7][C:6]([NH:9][NH:10]C(OC(C)(C)C)=O)=[CH:5][CH:4]=1.[F:20][C:21]([F:40])([F:39])[C:22]([NH:24][CH2:25][C:26]1[C:27]([F:38])=[CH:28][C:29]([Cl:37])=[C:30]([CH:36]=1)[C:31]([N:33]=[C:34]=[O:35])=O)=[O:23].FC(F)(F)C(O)=O>C(Cl)Cl>[Cl:37][C:29]1[C:30]([C:31]2[NH:33][C:34](=[O:35])[N:9]([C:6]3[CH:7]=[CH:8][C:3]([C:2]([F:1])([F:19])[F:18])=[CH:4][CH:5]=3)[N:10]=2)=[CH:36][C:26]([CH2:25][NH:24][C:22](=[O:23])[C:21]([F:40])([F:39])[F:20])=[C:27]([F:38])[CH:28]=1
Reactant: O=C=NC(=O)c1cc(CNC(=O)C(F)(F)F)c(F)cc1Cl
Reactant: CC(C)(C)OC(=O)NNc1ccc(C(F)(F)F)cc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: O=C(NCc1cc(-c2nn(-c3ccc(C(F)(F)F)cc3)c(=O)[nH]2)c(Cl)cc1F)C(F)(F)F
Yield: 6.7 %

Procedure:
The title compound was prepared according to the procedure described in Example-83 by using tert-butyl 2-(4-(trifluoromethyl)phenyl)hydrazinecarboxylate (Intermediate-53, 0.300 g), 5-((2,2,2-trifluoroacetamido)methyl)-2-chloro-4-fluorobenzoyl isocyanate (Intermediate-69, 0.300 g), DCM (20 mL), trifluoro acetic acid (5.0 mL) to afford 0.030 g of the desired product. 1H NMR (400 MHz, DMSO d6): δ 4.49 (m, 2H), 7.74-7.77 (m, 1H), 7.78-7.80 (m, 1H), 7.87 (d, J=5.1 Hz, 2H), 8.19 (d, J=4.2 Hz, 2H), 10.06 (m, 1H), 12.76 (s, 1H); MS (m/z): 467.15 (M+H)+.
Reaction SMILES: [OH:1][C:2]1[C:7]([C:8]([CH2:11][CH3:12])([CH3:10])[CH3:9])=[CH:6][C:5]([C:13]([CH2:16][CH3:17])([CH3:15])[CH3:14])=[CH:4][C:3]=1[N:18]1[N+:22]([O-])=[C:21]2[CH:24]=[CH:25][CH:26]=[CH:27][C:20]2=[N:19]1.C(O)CCC.[OH-].[Na+].C1C2C(=O)C3C(=CC=CC=3)C=2C=CC=1>O>[OH:1][C:2]1[C:7]([C:8]([CH2:11][CH3:12])([CH3:10])[CH3:9])=[CH:6][C:5]([C:13]([CH2:16][CH3:17])([CH3:15])[CH3:14])=[CH:4][C:3]=1[N:18]1[N:22]=[C:21]2[CH:24]=[CH:25][CH:26]=[CH:27][C:20]2=[N:19]1
Reactant: CCC(C)(C)c1cc(-n2nc3ccccc3[n+]2[O-])c(O)c(C(C)(C)CC)c1
Agent: O=C1c2ccccc2-c2ccccc21
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCCCO
Product: CCC(C)(C)c1cc(-n2nc3ccccc3n2)c(O)c(C(C)(C)CC)c1
Reaction time: 2.5 h
Yield: 92.4 %

Procedure:
2-(2-hydroxy-3,5-di-t-amylphenyl)benzotriazole-N-oxide 23.2 g was added to a mixture of n-butanol 60 g, water 12 g and 97% sodium hydroxide 16.5 g, and 9-fluorenone 2.0 g was further added to the resultant mixture. The resultant mixture was heated to 80° C., and was further stirred at 80°~85° C. for 2.5 hours, thus the reduction reaction being completed. The reaction liquor was treated in the same manner as in Example 17 to recover butanol, and 1.8 g of 9-fluorenone catalyst was recovered as a fraction at 120°~130° C. under vacuum of 2~3 mmHg. After recovering the catalyst, the remaining material was washed with methanol to produce the desired product, i.e. 20.5 g of 2-(2-hydroxy-3,5-di-t-amylphenyl)benzotriazole having a melting point of 79°~80° C. at the yield of 92.8%.
Reaction SMILES: [OH:1][CH2:2][CH:3]1[NH:7][C:6](=[O:8])[CH2:5][CH2:4]1.N1C(C(O)=O)CCC1=O.C(N(CC)CC)C.[CH3:25][S:26](Cl)(=[O:28])=[O:27]>ClCCl>[CH3:25][S:26]([O:1][CH2:2][CH:3]1[NH:7][C:6](=[O:8])[CH2:5][CH2:4]1)(=[O:28])=[O:27]
Reactant: CS(=O)(=O)Cl
Reactant: O=C1CCC(CO)N1
Agent: O=C1CCC(C(=O)O)N1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OCC1CCC(=O)N1
Temperature: 25 °C
Reaction time: 18 h
Yield: 83.6 %

Procedure:
An ice cold solution of 5-(hydroxymethyl)pyrrolidin-2-one (1.5 g, 13 mmol) prepared from 2-pyrrolidone-5-carboxylic acid (Valesinas et al., J. Org. Chem. 1992, 57, 2156-2160) in 20 mL of dichloromethane was treated with triethylamine (2.4 g, 23.5 mmol) and methylsulfonyl chloride (2.2 g, 19 mmol). The resulting solution was stirred at room temperature for 18 h. The reaction mixture was filtered to remove triethylamine hydrochloride and the filtrate was evaporated under reduced pressure. The crude, oily material was purified by chromatography (silica gel; 10% methanol in chloroform) to give 2.1 g of 5-(methanesulfonyloxymethyl)pyrrolidin-2-one as an oil which solidified upon addition of ether.
Reaction SMILES: C([O:5][C:6](=[O:53])[CH:7]([N:12]1[C:18](=[O:19])[CH:17]([NH:20][C:21](=[O:48])[CH:22]([S:38]CC2C=CC(OC)=CC=2)[CH2:23][CH2:24][CH2:25][CH2:26][N:27]2[C:31](=[O:32])[C:30]3=[CH:33][CH:34]=[CH:35][CH:36]=[C:29]3[C:28]2=[O:37])[CH2:16][C:15]2[CH:49]=[CH:50][CH:51]=[CH:52][C:14]=2[CH2:13]1)[CH2:8][CH:9]([CH3:11])[CH3:10])(C)(C)C.C1(OC)C=CC=CC=1.C(Cl)(Cl)(Cl)Cl>ClCCl.C([O-])(=O)C.[Hg+2].C([O-])(=O)C>[SH:38][CH:22]([CH2:23][CH2:24][CH2:25][CH2:26][N:27]1[C:28](=[O:37])[C:29]2=[CH:36][CH:35]=[CH:34][CH:33]=[C:30]2[C:31]1=[O:32])[C:21]([NH:20][CH:17]1[C:18](=[O:19])[N:12]([CH:7]([CH2:8][CH:9]([CH3:11])[CH3:10])[C:6]([OH:53])=[O:5])[CH2:13][C:14]2[CH:52]=[CH:51][CH:50]=[CH:49][C:15]=2[CH2:16]1)=[O:48]
Reactant: COc1ccc(CSC(CCCCN2C(=O)c3ccccc3C2=O)C(=O)NC2Cc3ccccc3CN(C(CC(C)C)C(=O)OC(C)(C)C)C2=O)cc1
Agent: CC(=O)[O-]
Agent: [Hg+2]
Solvent: ClC(Cl)(Cl)Cl
Solvent: ClCCl
Solvent: COc1ccccc1
Product: CC(C)CC(C(=O)O)N1Cc2ccccc2CC(NC(=O)C(S)CCCCN2C(=O)c3ccccc3C2=O)C1=O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Combine 2-(4-(2-(p-methoxybenzylthio)-6-phthalimidohexanoyl-amino)-3-oxo-1,3,4,5-tetrahydro-benzo[c]azepin-2-yl)-4-methyl-valeric acid t-butyl ester (0.20 mmol), mercury (II) acetate (0.084 g, 0.26 mmol), and anisole (0.23 mL, 2.1 mmol) in dichloromethane (6.6 mL). Cool in an ice bath and degas by repeatedly cycles of vacuum and filling the vessel with nitrogen gas. Add trifluoroacetic acid (2.5 mL). After 1 hour, warm to ambient temperature. After 3 hours, purge with hydrogen sulfide (gas) for about 10 minutes. Filter and evaporate in vacuo to give a residue. Repeatedly, combine the residue and carbon tetrachloride and evaporate in vacuo to give the title compound.
Reaction SMILES: [C:1]([C:20]1[CH:26]=[CH:25][C:23](N)=[CH:22][CH:21]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)=O.N([O-])=O.[Na+].[BrH:35]>O.[Cu]Br>[C:1]([C:20]1[CH:26]=[CH:25][C:23]([Br:35])=[CH:22][CH:21]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Nc1ccc(C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Reactant: Br
Agent: [Cu]Br
Agent: O=N[O-]
Agent: [Na+]
Solvent: CC(C)=O
Solvent: O
Product: Brc1ccc(C(c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Reaction time: 0.5 h
Yield: 86 %

Procedure:
25 parts by weight of 4-tritylaniline, 400 parts by weight of acetone, and 162 parts by weight of hydrobromic acid were put into a reaction vessel and stirred. While cooling the vessel in an ice bath, a solution of 7 parts by weight of sodium nitrite dissolved in 100 parts by weight of water was slowly added dropwise thereto. After the dropwise addition was complete, stirring was carried out for 30 minutes in an ice bath. Slowly added dropwise to this solution in an ice bath was a solution of 17.4 parts by weight of copper (I) bromide that had been dissolved in 31.5 parts by weight of hydrobromic acid. After the dropwise addition was complete, stirring was carried out at room temperature for 2 hours. After the reaction, a precipitate deposited in the reaction solution was collected by filtration, thus giving 25.8 parts by weight of 4-tritylbromobenzene (yield: 86%).
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[C:9]([C:11]2[CH2:15][C@:14]([C:20]3[CH:25]=[C:24]([Cl:26])[C:23]([Cl:27])=[C:22]([Cl:28])[CH:21]=3)([C:16]([F:19])([F:18])[F:17])[O:13][N:12]=2)[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.CN(C)C=O.C(Cl)(=O)C(Cl)=O.Cl.[OH-].[Na+].C(N(CC)CC)C.[S:50]1[CH2:53][CH:52]([NH2:54])[CH2:51]1>ClCCl>[CH3:1][C:2]1[CH:10]=[C:9]([C:11]2[CH2:15][C@:14]([C:20]3[CH:25]=[C:24]([Cl:26])[C:23]([Cl:27])=[C:22]([Cl:28])[CH:21]=3)([C:16]([F:18])([F:19])[F:17])[O:13][N:12]=2)[CH:8]=[CH:7][C:3]=1[C:4]([NH:54][CH:52]1[CH2:53][S:50][CH2:51]1)=[O:6]
Reactant: Cc1cc(C2=NO[C@@](c3cc(Cl)c(Cl)c(Cl)c3)(C(F)(F)F)C2)ccc1C(=O)O
Reactant: NC1CSC1
Agent: Cl
Agent: O=C(Cl)C(=O)Cl
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1cc(C2=NO[C@@](c3cc(Cl)c(Cl)c(Cl)c3)(C(F)(F)F)C2)ccc1C(=O)NC1CSC1
Temperature: 30 °C
Reaction time: 0.33 h

Procedure:
To a solution of 2-methyl-4-[(5S)-5-(3,4,5-trichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]benzoic acid (28.72 mmol, 13 g) in dichloromethane (100 mL) and N,N-dimethylformamide (0.2867 mmol, 0.0210 g) was added oxalyl chloride (4.836 g) dropwise at room temperature and under argon (the liberated hydrochloric acid gas was scrubbed with a sodium hydroxide 0.5N solution). The mixture was stirred at room temperature for 1 h and at 30° C. for 20 min until the gas evolution ceased. The reaction mixture was concentrated to dryness and redissolved in dichloromethane (100 mL), triethylamine (71.81 mmol, 7.340 g) was added at 0-5° C. under argon followed by dropwise addition of thietan-3-amine (28.72 mmol, 2.561 g). The mixture was allowed to warm to room temperature and stirred for 16 h. The mixture was extracted with aqueous hydrochloric acid (0.5N), water, brine, dried over MgSO4, filtered and evaporated affording the crude product. Purification over silica gel (eluent: CH2Cl2/EtOAc) yielded the title compound. LCMS (Method GR) RT 1.25 min, [M+H]+ 523/525; 1H-NMR (CDCl3, 400 MHz): 2.45 (s, 3H), 3.35 (m, 2H), 3.50 (m, 2H), 3.60 (d, 1H), 74.10 (d, 1H), 5.40 (q, 1H), 6.20 (d, NH), 7.40 (s, 1H), 7.51 (d, 1H), 7.40 (s, 1H), 7.50 (s, 2H), 7.65 (s, 2H). 19F-NMR (CDCl3, 376 MHz): −79.43.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([NH:12][NH2:13])[CH2:9][N:8]=[C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)[C:6]=2[CH:20]=1.[C:21]([O:26][CH3:27])(=[O:25])[C:22]([CH3:24])=O>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([NH:12][N:13]=[C:22]([C:21]([O:26][CH3:27])=[O:25])[CH3:24])[CH2:9][N:8]=[C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)[C:6]=2[CH:20]=1
Reactant: NNC1=Nc2ccc(Br)cc2C(c2ccccn2)=NC1
Reactant: COC(=O)C(C)=O
Product: COC(=O)C(C)=NNC1=Nc2ccc(Br)cc2C(c2ccccn2)=NC1

Procedure:
In the manner given in Example 1, 7-bromo-2-hydrazino-5-(2-pyridyl)-3H-1,4-benzodiazepine can be stirred with methyl pyruvate at room temperature to give 7-bromo-2-[[1-(methoxycarbonyl)ethylidene]hydrazino]-5-(2-pyridyl)-3H-1,4-benzodiazepine.
Reaction SMILES: [CH3:1][CH:2]([CH2:4][CH2:5][CH2:6]/[C:7](/[CH3:16])=[CH:8]/[CH2:9][CH2:10]/[C:11](/[CH3:15])=[CH:12]/[CH:13]=[O:14])[CH3:3].[N+:17]([CH2:20][CH3:21])([O-:19])=[O:18]>>[CH3:15][CH:11]([CH2:10][CH2:9][CH:8]=[C:7]([CH3:16])[CH2:6][CH2:5][CH:4]=[C:2]([CH3:1])[CH3:3])[CH2:12][CH:13]([OH:14])[CH:20]([N+:17]([O-:19])=[O:18])[CH3:21]
Reactant: C/C(=C\C=O)CC/C=C(\C)CCCC(C)C
Reactant: CC[N+](=O)[O-]
Product: CC(C)=CCCC(C)=CCCC(C)CC(O)C(C)[N+](=O)[O-]
Yield: 90 %

Procedure:
To 2.93 g of 3 was added 5 mL of nitroethane with stirring. Approximately 5-6 g of Amberlyst A-21 was added, and the mixture was stirred at room temperature overnight. The mixture was filtered and the ion exchange resin was rinsed four times with 25 mL of dichloromethane. The filtrate was dried over anhydrous MgSO4, and the solvent was removed by rotary evaporation, which afforded 3.53 g (90%) of a mixture of stereoisomers of the desired nitro alcohol 4. 1H NMR δ (ppm) 5.2 (t, CH3C(CH3)═CH and CH2C(CH3)═CH), 4.4 (m, CHNO2), 2.2 (br s, CHOH), 2.0 (m, C═CHCH2CH2C(CH3)═CHCH2), 1.6-1.7 (all s, CH3C(CH3)═CHCH2CH2CCH3), 1.5 (d, CH3CHNO2), 1.2-1.5 (m, CH2CH(CH3)CH2), 0.9 (d, CH2CH(CH3)CH2).
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[OH:6][CH2:7][CH2:8][C:9]1[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][CH:10]=1.O>C(Cl)Cl>[CH3:1][S:2]([O:6][CH2:7][CH2:8][C:9]1[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][CH:10]=1)(=[O:4])=[O:3]
Reactant: N#Cc1ccc(CCO)cc1
Reactant: CS(=O)(=O)Cl
Solvent: O
Solvent: ClCCl
Product: CS(=O)(=O)OCCc1ccc(C#N)cc1
Temperature: 25 °C

Procedure:
MsCl (18.6 g; 164 mmol) was added to a stirred solution of 4-(2-hydroxyethyl)benzonitrile (20 g; 136 mmol) and TEA (20.6 g; 204 mmol) in DCM (200 mL) at 0° C. The reaction mixture was stirred at rt. until tlc indicated that the reaction was complete. Water (200 mL) was added and the organic layer was separated, dried and concentrated to give the sub-title compound in a quantitative yield.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]2[CH:9]([C:10]([O:12][CH:13]([CH3:15])[CH3:14])=[O:11])[CH2:8][CH2:7][CH2:6][N:5]2[CH:16]=1.CN(C)[C:19]([C:21]1[CH:26]=[CH:25][C:24]([CH3:27])=[CH:23][CH:22]=1)=[O:20]>>[C:24]1([CH3:27])[CH:25]=[CH:26][C:21]([C:19]([C:16]2[N:5]3[CH2:6][CH2:7][CH2:8][CH:9]([C:10]([O:12][CH:13]([CH3:14])[CH3:15])=[O:11])[C:4]3=[CH:3][C:2]=2[CH3:1])=[O:20])=[CH:22][CH:23]=1
Reactant: Cc1cc2n(c1)CCCC2C(=O)OC(C)C
Reactant: Cc1ccc(C(=O)N(C)C)cc1
Product: Cc1ccc(C(=O)c2c(C)cc3n2CCCC3C(=O)OC(C)C)cc1

Procedure:
In accordance with the method of Example 8, isopropyl 2-methyl-5,6,7,8-tetrahydropyrrolo[1,2-a]pyridine-8-carboxylate is condensed with N,N-dimethyl-p-toluamide, to produce isopropyl 3-p-toluoyl-2-methyl-5,6,7,8-tetrahydropyrrolo[1,2-a]pyridine-8-carboxylate (XI, R=CH3, L=p-CH3, R2 =iC3H7, n=1).
Reaction SMILES: [OH-].[Na+].[CH:3]1([C:9]2[C:10]3[CH:11]=[CH:12][C:13]([C:28]([O:30]C)=[O:29])=[CH:14][C:15]=3[N:16]3[CH2:22][C:21](=[O:23])[CH2:20][C:19]4[CH:24]=[CH:25][CH:26]=[CH:27][C:18]=4[C:17]=23)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.Cl>CO.O1CCCC1>[CH:3]1([C:9]2[C:10]3[CH:11]=[CH:12][C:13]([C:28]([OH:30])=[O:29])=[CH:14][C:15]=3[N:16]3[CH2:22][C:21](=[O:23])[CH2:20][C:19]4[CH:24]=[CH:25][CH:26]=[CH:27][C:18]=4[C:17]=23)[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]1
Reactant: COC(=O)c1ccc2c(C3CCCCC3)c3n(c2c1)CC(=O)Cc1ccccc1-3
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: O=C1Cc2ccccc2-c2c(C3CCCCC3)c3ccc(C(=O)O)cc3n2C1
Temperature: 90 °C
Yield: 92.7 %

Procedure:
Sodium hydroxide (0.2 mL of 1 N, 0.2 mmol) was added to a solution of the Methyl 13-cyclohexyl-6,7-dihydro-6-oxo-5H-indolo[2,1-a][2]benzazepine-10-carboxylate (20 mg, 0.052 mmol) in methanol (0.5 mL) and tetrahydrofuran (0.5 mL) in a microwave vial. The vial was sealed and the contents heated at 90° C. for 5 min in a microwave apparatus. The solution was acidified with dilute hydrochloric acid to precipitate the crude acid. The solid was collected and purified on the Shimadzu preparative liquid chromatograph. The product containing fraction was concentrated on a Speed Vac® to leave the titled compound as a white solid (18 mg, 92%). ESI-MS m/z 374 (MH+); 1H NMR (500 MHz, ACETONE-D6) δ 1.22-1.35 (m, 1 H) 1.41-1.58 (m, 2 H) 1.59-1.70 (m, 1 H) 1.73-1.85 (m, 2 H) 1.92-2.00 (m, 1 H) 2.11-2.26 (m, 3 H) 3.04 (m, 1 H) 3.60 (d, J=14.04 Hz, 1 H) 3.97 (d, J=13.73 Hz, 1 H) 4.56 (d, J=18.31 Hz, 1 H) 5.19 (d, J=18.31 Hz, 1 H) 7.51 (m, 2 H) 7.57 (t, J=7.32 Hz, 1 H) 7.66 (d, J=7.63 Hz, 1 H) 7.81 (dd, J=8.39, 1.37 Hz, 1 H) 8.03 (d, J=8.24 Hz, 1H 8.23 (s, 3 H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:9])=[C:6]([OH:8])[CH:7]=1.[CH3:10][N:11]1[CH:15]=[C:14]([CH2:16]O)[N:13]=[N:12]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1.C(O)(=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:9])=[C:6]([CH:7]=1)[O:8][CH2:16][C:14]1[N:13]=[N:12][N:11]([CH3:10])[CH:15]=1
Reactant: Cn1cc(CO)nn1
Reactant: Oc1cc(Br)ccc1F
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: Cn1cc(COc2cc(Br)ccc2F)nn1
Temperature: 25 °C
Reaction time: 12 h
Yield: 66.4 %

Procedure:
An ice-cooled solution of 5-bromo-2-fluorophenol (1.91 g, 10 mmol), (1-methyl-1H-[1,2,3]triazol-4-yl)methanol (1.24 g, 11 mmol) and triphenylphosphine (3.93 g, 15 mmol) in tetrahydrofuran (50 ml) was treated dropwise with diisopropyl azodicarboxylate (3.03 g, 15 mmol) over 10 min. The resulting mixture was stirred to ambient temperature over 12 h and then glacial acetic acid (1 ml) was added. The reaction mixture was concentrated in vacuo then partitioned between ethyl acetate and 0.01N sodium hydroxide solution. The organics were washed with water, brine, dried over anhydrous magnesium sulphate and concentrated to give an oil. This oil was purified by chromatography on silica gel, eluting with isohexane on a gradient of ethyl acetate (20-50%). Product-containing fractions were concentrated and the resulting residue triturated with 10% ether in isohexane to furnish 4-(5-bromo-2-fluorophenoxymethyl)-1-methyl-1H-[1,2,3]triazole as a white solid (1.9 g, 66%): δH (360 MHz, d6-DMSO) 4.06 (3H, s), 5.25 (2H, s), 7.10-7.20 (2H, m), 7.55-7.70 (1H, m), 8.19 (1H, s).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]([C:11]2[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:12]=2[NH:18][C:19]([C:21]2[CH:26]=[CH:25][C:24]([S:27]([CH3:33])(=[N:29][CH2:30][CH2:31]Br)=[O:28])=[CH:23][CH:22]=2)=[O:20])=[O:10])=[N:6][CH:7]=1.[CH2:34]([NH:36][CH2:37][CH3:38])[CH3:35]>CN(C=O)C.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]([C:11]2[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:12]=2[NH:18][C:19]([C:21]2[CH:26]=[CH:25][C:24]([S:27]([CH3:33])(=[N:29][CH2:30][CH2:31][N:36]([CH2:37][CH3:38])[CH2:34][CH3:35])=[O:28])=[CH:23][CH:22]=2)=[O:20])=[O:10])=[N:6][CH:7]=1
Reactant: CCNCC
Reactant: CS(=O)(=NCCBr)c1ccc(C(=O)Nc2ccc(Cl)cc2C(=O)Nc2ccc(Cl)cn2)cc1
Solvent: CN(C)C=O
Solvent: O
Product: CCN(CC)CCN=S(C)(=O)c1ccc(C(=O)Nc2ccc(Cl)cc2C(=O)Nc2ccc(Cl)cn2)cc1
Reaction time: 2 h
Yield: 60 %

Procedure:
To a stirring solution of S-[4-(N-{2-[N-(5-chloro(2-pyridyl))carbamoyl]-4-chlorophenyl}carbamoyl)phenyl]-S-methyl-N-[2-bromo-ethyl]sulfoximide (150 mg, 0.00026 mol) in DMF(0.7 mL) was added diethyl amine (1 mL) at 25° C. Reaction mixture was stirred at same temperature for 2 hr. Reaction mixture was diluted with water and filtered. Drying afforded 85 mg of titled compound in 60% yield.