Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH:10](O)[CH2:11][CH2:12][CH3:13])=[CH:9][C:4]=2[O:3][CH2:2]1.[SH:15][CH2:16][C:17]([OH:19])=[O:18].C1C=CC=CC=1>CC1(C)C2(CS(O)(=O)=O)C(CC1CC2)=O.CCOCC>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH:10]([S:15][CH2:16][C:17]([OH:19])=[O:18])[CH2:11][CH2:12][CH3:13])=[CH:9][C:4]=2[O:3][CH2:2]1
Reactant: CCCC(O)c1ccc2c(c1)OCO2
Reactant: O=C(O)CS
Agent: CC1(C)C2CCC1(CS(=O)(=O)O)C(=O)C2
Solvent: c1ccccc1
Solvent: CCOCC
Product: CCCC(SCC(=O)O)c1ccc2c(c1)OCO2
Yield: 89.3 %

Procedure:
A mixture of 103 g of 1-(1,3-benzodioxol-5-yl)-1-butanol, 73.3 g of mercaptoacetic acid, 0.1 g of D-10-camphorsulfonic acid and 500 ml of benzene was heated under reflux for 2 h. 2,000 ml of ether was added to the reaction mixture. After washing with water, the product was redissolved in 750 ml of 1NNaOH and then in 100 ml thereof. The solution thus obtained was washed with ether and then with chloroform, acidified with concentrated hydrochloric acid and extracted with 800 ml and then 400 ml of ethyl acetate. The extract was washed with water, dried over magnesium sulfate and concentrated under reduced pressure to obtain 132 g of the crude product. It was purified according to silica gel column chromatography (ethyl acetate/hexane/formic acid=100:900:1) to obtain 127 g of the intended compound in the form of a colorless oil. This oil was crystallized from n-hexane to obtain 115 g of the titled compound as a white crystalline powder. It was found to have a melting point of 59° to 61° C.
Reaction SMILES: [CH3:1][CH:2]([CH2:4][CH2:5][CH2:6][C@H:7]([C@@H:9]1[C@:27]2([CH3:28])[C@H:12]([C@H:13]3[C@H:24]([CH2:25][CH2:26]2)[C@:22]2([CH3:23])[C:16]([CH2:17][C@H:18]([CH2:20][CH2:21]2)[OH:19])=[CH:15][CH2:14]3)[CH2:11][CH2:10]1)[CH3:8])[CH3:3].[C:29](O)(=[O:33])[C@H:30]([CH3:32])[OH:31].C1(C)C=CC(S(O)(=O)=O)=CC=1.O>C1(C)C=CC=CC=1>[OH:31][C@@H:30]([CH3:32])[C:29]([O:19][C@H:18]1[CH2:20][CH2:21][C@@:22]2([CH3:23])[C:16](=[CH:15][CH2:14][C@@H:13]3[C@@H:24]2[CH2:25][CH2:26][C@@:27]2([CH3:28])[C@H:12]3[CH2:11][CH2:10][C@@H:9]2[C@H:7]([CH3:8])[CH2:6][CH2:5][CH2:4][CH:2]([CH3:1])[CH3:3])[CH2:17]1)=[O:33]
Reactant: C[C@H](O)C(=O)O
Reactant: CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: Cc1ccccc1
Product: CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](OC(=O)[C@H](C)O)CC[C@]4(C)[C@H]3CC[C@]12C
Reaction time: 4 h

Procedure:
A solution of 3.86 g of cholesterol and 0.85 ml of L-(+)-lactic acid (90% in water) in 80 ml of toluene is boiled for 1 hour. The water is separated, the cooled reaction mixture is treated with 0.3 g of p-toluene-sulphonic acid and boiled for a further 4 hours. The reaction mixture is treated with 30 ml of water and extracted with ether. The organic phase is dried over sodium sulphate and concentrated. The residue is purified on silica gel, with petroleum ether/ether 4:1 used as the elution agent. There are obtained 1.5 g of cholest-5-en-3β-yl (S)-2-hydroxypropionate, m.p. 120°-122° C.
Reaction SMILES: Cl[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:4].[NH:11]1[CH:15]=[CH:14][CH:13]=[N:12]1.C([O-])([O-])=O.[K+].[K+]>CC#N.CCOC(C)=O>[C:5]1([C:3](=[O:4])[CH2:2][N:11]2[CH:15]=[CH:14][CH:13]=[N:12]2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: c1cn[nH]c1
Reactant: O=C(CCl)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: CCOC(C)=O
Product: O=C(Cn1cccn1)c1ccccc1
Reaction time: 5 h

Procedure:
To a solution of 1.5 g (9.7 mmol) of 2-chloroacetophenone in 10 mL of MeCN, 0.7 g (10.3 mmol) of pyrazole was added. After all the solids dissolved, 1.4 g (10.1 mmol) of ground K2CO3 was added and the mixture was stirred for 5 h. The reaction was diluted with EtOAc, filtered, and the solid was washed with EtOAc. The filtrate was washed with water and brine, then was dried and concentrated. The residue was chromatographed on a flash column using a gradient of 10-50% EtOAc-hexane to isolate desired product.
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:13]=[CH:12][C:8]([C:9](Cl)=[O:10])=[CH:7][CH:6]=1)(=[O:3])[CH3:2].[Br:14][C:15]1[CH:19]=[N:18][N:17]([CH3:20])[C:16]=1[C:21]1[CH:22]=[C:23]([CH:25]=[CH:26][C:27]=1[O:28][CH2:29][C:30]([CH3:35])([N+:32]([O-])=O)[CH3:31])[NH2:24].C(N(CC)C(C)C)(C)C>ClCCl>[C:1]([NH:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([NH:24][C:23]2[CH:25]=[CH:26][C:27]([O:28][CH2:29][C:30]([NH2:32])([CH3:35])[CH3:31])=[C:21]([C:16]3[N:17]([CH3:20])[N:18]=[CH:19][C:15]=3[Br:14])[CH:22]=2)=[O:10])=[CH:7][CH:6]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)Nc1ccc(C(=O)Cl)cc1
Reactant: Cn1ncc(Br)c1-c1cc(N)ccc1OCC(C)(C)[N+](=O)[O-]
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(=O)Nc1ccc(C(=O)Nc2ccc(OCC(C)(C)N)c(-c3c(Br)cnn3C)c2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 22.4 %

Procedure:
4-Acetamidobenzoyl chloride (11 mg, 0.06 mmol) was added to a solution of 3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-(2-methyl-2-nitropropoxy)aniline (18 mg, 0.05 mmol) and N,N-diisopropylethylamine (10 μl, 0.06 mmol) in dichloromethane (0.5 mL) and the mixture was stirred at room temperature. After 1 h, the solution was diluted with dichloromethane, washed with 1M hydrochloric acid and saturated sodium bicarbonate, dried with sodium sulfate, filtered, and evaporated to dryness. The residue was dissolved in methanol (0.5 mL). Acetic acid (0.1 mL) was added followed by zinc dust (33 mg) and the mixture was stirred at room temperature. After 4 h, the suspension was made basic with ammonium hydroxide and extracted twice with ethyl acetate. The combined extracts were evaporated to dryness, purified by preparative LCMS and lyophilized to give the product (5.6 mg, 22%) as a TFA-salt. LCMS m/z (%)=502.3 (M+H 81Br 42.9%), 500.4 (M+H 79Br 52.1%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.16 (s, 3 H), 1.18 (s, 3 H), 2.08 (s, 3 H), 3.67 (s, 3 H), 3.82 (d, J=9.60 Hz, 1 H), 3.98 (d, J=9.85 Hz, 1 H), 7.27 (d, J=9.09 Hz, 1 H), 7.67 (s, 1 H), 7.69 (d, J=2.78 Hz, 1 H), 731 (d, J=8.84 Hz, 2 H), 7.85-7.91 (m, 3 H), 7.91 (d, J=8.84 Hz, 2 H), 7.95 (dd, J=8.97, 2.65 Hz, 1 H), 10.22 (s, 1 H), 10.23 (s, 1 H).
Reaction SMILES: [Br:1][C:2]1[CH:11]=[CH:10][C:5]2[N:6]=[C:7](Cl)[S:8][C:4]=2[CH:3]=1.[CH3:12][CH:13]([NH2:15])[CH3:14].C(N(CC)CC)C>CN(C=O)C>[Br:1][C:2]1[CH:11]=[CH:10][C:5]2[N:6]=[C:7]([NH:15][CH:13]([CH3:14])[CH3:12])[S:8][C:4]=2[CH:3]=1
Reactant: Clc1nc2ccc(Br)cc2s1
Reactant: CC(C)N
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CC(C)Nc1nc2ccc(Br)cc2s1
Yield: 64 %

Procedure:
A microwave reaction vial was charged with 6-bromo-2-chlorobenzo[d]thiazole (300 mg, 1.21 mmol), propan-2-amine (75 mg, 1.27 mmol), triethylamine (183 mg, 1.81 mmol) and 2.4 mL DMF. The vial was sealed, and the mixture was irradiated in the microwave for 20 min at 150° C. The reaction mixture was concentrated twice from toluene and purified by silica gel chromatography (0-50% 90/10 CH2Cl2/MeOH in CH2Cl2), which provided 6-bromo-N-isopropylbenzo[d]thiazol-2-amine (210 mg, 64%) as a white solid. MS (ESI pos. ion) m/z calc'd for C10H11BrN2S: 271.2/273.2. found 271.0/273.0.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9](=[O:24])[CH2:10][N:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]1>CN(C(OC)OC)C>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9](=[O:24])[C:10]([N:11]1[CH2:12][CH2:13][N:14]([C:17]([O:19][C:20]([CH3:21])([CH3:23])[CH3:22])=[O:18])[CH2:15][CH2:16]1)=[CH:10][N:11]([CH3:16])[CH3:12]
Reactant: CC(C)(C)OC(=O)N1CCN(CC(=O)c2ccc(Cl)cc2Cl)CC1
Agent: COC(OC)N(C)C
Product: CN(C)C=C(C(=O)c1ccc(Cl)cc1Cl)N1CCN(C(=O)OC(C)(C)C)CC1

Procedure:
1 mmol of tert-butyl 4-[2-(2,4-dichlorophenyl)-2-oxoethyl]piperazinecarboxylate was heated to 80° C. in neat N,N-dimethylformamidedimethyl acetal for six hours. The reaction mixture was concentrated in vacuo and purified by trituration with diethyl ether to obtain tert-butyl 4-{2-(2,4-dichlorophenyl)-1-[(dimethylamino)methylene]-2-oxoethyl}piperazinecarboxylate.
Reaction SMILES: C([O:5][C:6]([CH:8]1[CH:12]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[C:14]=2[F:20])[C:11]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=2[F:30])([C:21]#[N:22])[CH:10]([CH2:31][C:32]2([C:36](C)(C)[O:37][SiH2]C(C)(C)C)[CH2:35][CH2:34][CH2:33]2)[NH:9]1)=[O:7])(C)(C)C.[F:45][C:46]([F:51])([F:50])[C:47]([OH:49])=[O:48]>ClCCl>[F:45][C:46]([F:51])([F:50])[C:47]([OH:49])=[O:48].[Cl:19][C:15]1[C:14]([F:20])=[C:13]([CH:12]2[C:11]([C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=3[F:30])([C:21]#[N:22])[CH:10]([CH2:31][C:32]3([CH2:36][OH:37])[CH2:33][CH2:34][CH2:35]3)[NH:9][CH:8]2[C:6]([OH:7])=[O:5])[CH:18]=[CH:17][CH:16]=1
Reactant: CC(C)(C)OC(=O)C1NC(CC2(C(C)(C)O[SiH2]C(C)(C)C)CCC2)C(C#N)(c2ccc(Cl)cc2F)C1c1cccc(Cl)c1F
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: N#CC1(c2ccc(Cl)cc2F)C(CC2(CO)CCC2)NC(C(=O)O)C1c1cccc(Cl)c1F
Yield: 100 %

Procedure:
In a manner similar to the method described in Example 25a, rac-(2R,3S,4R,5S)-5-[1-(tert-butyl-dimethyl-silanyloxymethyl)-cyclobutylmethyl]-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-pyrrolidine-2-carboxylic acid tert-butyl ester prepared in Example 115b (0.7 g, 1 mmol) was reacted with trifluoroacetic acid in dichloromethane at room temperature to give rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(1-hydroxymethyl-cyclobutylmethyl)-pyrrolidine-2-carboxylic acid trifluoroacetic acid as a white solid (0.6 g, 100%).
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[CH:5][CH:4]=1.[NH2:14][C:15]1[CH:24]=[CH:23][C:22]2[C:17](=[N:18][C:19]([C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=3)=[CH:20][CH:21]=2)[N:16]=1.C(#N)C>O>[CH3:32][O:31][C:28]1[CH:27]=[CH:26][C:25]([C:19]2[N:18]=[C:17]3[C:22]([CH:23]=[CH:24][C:15]([NH:14][C:7](=[O:9])[C:6]4[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:13])[F:12])=[CH:11][CH:10]=4)=[N:16]3)=[CH:21][CH:20]=2)=[CH:30][CH:29]=1
Reactant: COc1ccc(-c2ccc3ccc(N)nc3n2)cc1
Reactant: O=C(O)c1ccc(C(F)(F)F)cc1
Solvent: CC#N
Solvent: O
Product: COc1ccc(-c2ccc3ccc(NC(=O)c4ccc(C(F)(F)F)cc4)nc3n2)cc1
Temperature: 4 °C
Yield: 57 %

Procedure:
The procedure is analogous to that described in Example 1 below but starting with 4-trifluoromethylbenzoic acid (2.7 g), N,N'-carbonyldiimidazole (2.3 g) and 2-amino-7-(4-methoxyphenyl)-1,8-naphthyridine (2.5 g). The product obtained by precipitation in water (3.3 g; m.p. 144°-146° C.) is dissolved in boiling acetonitrile (100 cc). After cooling for 3 hours at 4° C., the crystallized solid is separated by filtration, washed with acetonitrile (2×10 cc) and dried at 40° C. under reduced pressure (0.07 kPa). N-[7-(4-Methoxyphenyl)-1,8-naphthyridin-2-yl]-4-trifluoromethylbenzamide (2.4 g), m.p. 148° C., is obtained.
Reaction SMILES: CC(C)([O-])C.[K+].[CH:7]([C:9]1[CH:14]=[C:13]([CH3:15])[C:12]([OH:16])=[C:11]([CH3:17])[CH:10]=1)=[O:8].Br[CH2:19][CH2:20][CH2:21][CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24]>CN(C=O)C>[CH:7]([C:9]1[CH:14]=[C:13]([CH3:15])[C:12]([O:16][CH2:19][CH2:20][CH2:21][CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])=[C:11]([CH3:17])[CH:10]=1)=[O:8]
Reactant: CCOC(=O)CCCCBr
Reactant: Cc1cc(C=O)cc(C)c1O
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)CCCCOc1c(C)cc(C=O)cc1C
Temperature: 110 °C

Procedure:
Potassium tert-butoxide (2.1 g, mw 112.2, 18 mmol) was added to a solution of 4-formyl-2,6-dimethylphenol (2.5 g, mw 150.2, 17 mmol) in dry DMF (15 mL) and the resultant suspension stirred under N2 at 25° C. for 5 minutes. Ethyl 5-bromovalerate (2.8 mL, mw 209.1, ρ 1.32, 18 mmol) dissolved in dry DMF (15 mL) was added, and the reaction heated at 110° C. for 5 hours, following which DMF was removed at 60° C. and 2 mm Hg. The residue was taken up in ethyl acetate (125 mL), washed with water (25 mL), 1 N aqueous NaOH (25 mL), and brine (75 mL), dried over Na2SO4, filtered, and concentrated to yield 4.47 g (97%) of NMR and TLC (Rf 0.58, CHCl3 -methanol, 99:1) pure title product as an amber oil.
Reaction SMILES: Cl.[C:2]1([CH3:10])[CH:7]=[CH:6][C:5]([NH:8][NH2:9])=[CH:4][CH:3]=1.[CH2:11]([O:18][CH2:19][C:20]([CH3:27])([CH3:26])[C:21](=O)[CH2:22][C:23]#[N:24])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C([O-])(O)=O.[Na+]>CCO>[CH2:11]([O:18][CH2:19][C:20]([C:21]1[CH:22]=[C:23]([NH2:24])[N:8]([C:5]2[CH:6]=[CH:7][C:2]([CH3:10])=[CH:3][CH:4]=2)[N:9]=1)([CH3:26])[CH3:27])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: CC(C)(COCc1ccccc1)C(=O)CC#N
Reactant: Cc1ccc(NN)cc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Product: Cc1ccc(-n2nc(C(C)(C)COCc3ccccc3)cc2N)cc1
Temperature: 25 °C
Yield: 62 %

Procedure:
A solution of p-tolylhydrazine hydrochloride (1.99 g, 12.6 mmol) and 5-(benzyloxy)-4,4-dimethyl-3-oxopentanenitrile (4.00 g, 13.8 mmol, 80% purity) in EtOH was heated at reflux for 16 hr and then cooled to RT. The mixture was neutralized with saturated aqueous NaHCO3 solution and extracted with EtOAc. The organic extracts were washed with brine, dried (MgSO4) and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 80 g, MeOH in DCM, 0-5%, gradient elution) to afford the title compound, (2.62 g, 60%); Rt 3.05 min (Method 1 basic); m/z 336 (M+H)+ (ES+).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:44]=[CH:45][CH:46]=1)[CH2:5][N:6]1[C:10]([CH3:11])=[C:9]([C:12]2[C:20]3[C:15](=[N:16][CH:17]=[C:18]([C:21]4[CH:26]=[CH:25][C:24]([N:27]5[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]5)=[CH:23][CH:22]=4)[CH:19]=3)[N:14]([S:33]([C:36]3[CH:42]=[CH:41][C:39]([CH3:40])=[CH:38][CH:37]=3)(=[O:35])=[O:34])[CH:13]=2)[C:8]([CH3:43])=[N:7]1.C(N(CC)CC)C.[C:54](Cl)(=[O:56])[CH3:55]>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([CH:44]=[CH:45][CH:46]=1)[CH2:5][N:6]1[C:10]([CH3:11])=[C:9]([C:12]2[C:20]3[C:15](=[N:16][CH:17]=[C:18]([C:21]4[CH:26]=[CH:25][C:24]([N:27]5[CH2:28][CH2:29][N:30]([C:54](=[O:56])[CH3:55])[CH2:31][CH2:32]5)=[CH:23][CH:22]=4)[CH:19]=3)[N:14]([S:33]([C:36]3[CH:42]=[CH:41][C:39]([CH3:40])=[CH:38][CH:37]=3)(=[O:34])=[O:35])[CH:13]=2)[C:8]([CH3:43])=[N:7]1
Reactant: Cc1ccc(S(=O)(=O)n2cc(-c3c(C)nn(Cc4cccc(F)c4)c3C)c3cc(-c4ccc(N5CCNCC5)cc4)cnc32)cc1
Reactant: CC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)N1CCN(c2ccc(-c3cnc4c(c3)c(-c3c(C)nn(Cc5cccc(F)c5)c3C)cn4S(=O)(=O)c3ccc(C)cc3)cc2)CC1
Temperature: 25 °C
Yield: 92.2 %

Procedure:
A stirred solution of 3-(1-(3-fluorobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl)-5-(4-(piperazin-1-yl)phenyl)-1-tosyl-1H-pyrrolo[2,3-b]pyridine (100 mg, 0.157 mmol), triethylamine (47.8 mg, 0.473 mmol), DCM (3 ml) was added acetyl chloride (18.5 mg, 0.236 mmol) drop wise at 0° C. Reaction mass was gradually warmed to room temperature, reaction completed in an hour. Reaction mass was diluted with DCM and washed with water, dried over sodium sulfate and concentrated to give 98 mg (92.4% yield) of the titled compound. MS: m/z=677.2 (M+1).
Reaction SMILES: [C:1]([O:5][C:6](=[O:46])[NH:7][CH2:8][CH:9]([C:30]1[CH:35]=[CH:34][C:33](B2OC(C)(C)C(C)(C)O2)=[CH:32][C:31]=1[CH3:45])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][O:20][C:21]2[C:26]([Cl:27])=[CH:25][C:24]([CH3:28])=[CH:23][C:22]=2[Cl:29])=[CH:13][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].FC(F)(F)S(O[C:53]1[C:54]([CH2:59][CH2:60][CH2:61][O:62][CH3:63])=[N:55][CH:56]=[CH:57][CH:58]=1)(=O)=O>>[Cl:27][C:26]1[CH:25]=[C:24]([CH3:28])[CH:23]=[C:22]([Cl:29])[C:21]=1[O:20][CH2:19][CH2:18][O:17][C:14]1[CH:15]=[CH:16][C:11]([CH2:10][CH:9]([C:30]2[CH:35]=[CH:34][C:33]([C:53]3[C:54]([CH2:59][CH2:60][CH2:61][O:62][CH3:63])=[N:55][CH:56]=[CH:57][CH:58]=3)=[CH:32][C:31]=2[CH3:45])[CH2:8][NH:7][C:6](=[O:46])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[CH:12][CH:13]=1
Reactant: COCCCc1ncccc1OS(=O)(=O)C(F)(F)F
Reactant: Cc1cc(Cl)c(OCCOc2ccc(CC(CNC(=O)OC(C)(C)C)c3ccc(B4OC(C)(C)C(C)(C)O4)cc3C)cc2)c(Cl)c1
Product: COCCCc1ncccc1-c1ccc(C(CNC(=O)OC(C)(C)C)Cc2ccc(OCCOc3c(Cl)cc(C)cc3Cl)cc2)c(C)c1

Procedure:
Prepared according to the procedure described in EXAMPLE 7, step 2 using tert-butyl{3-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]phenyl}-2-[2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propyl}carbamate from EXAMPLE 9, step 1 and 2-(3-methoxypropyl)pyridin-3-yl trifluoromethanesulfonate (V.16) as starting materials. Purification by column chromatography on silica gel (Combi-Flash by ISCO), eluting with Hex/EtOAc (0 to 75%, in 30 min) afforded the desired compound as a colorless oil.
Reaction SMILES: ClC(Cl)(Cl)[C:3]([C:5]1[N:14]2[C:8]([CH2:9][N:10]([C:19]([C:21]3[CH:26]=[CH:25][C:24]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[CH3:33])=[C:23]([O:34][CH3:35])[CH:22]=3)=[O:20])[C:11]3[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=3[CH2:13]2)=[CH:7][CH:6]=1)=[O:4].[F:38][C:39]([F:49])([F:48])[C:40]1[CH:47]=[CH:46][CH:45]=[CH:44][C:41]=1[CH2:42][NH2:43]>>[CH3:35][O:34][C:23]1[CH:22]=[C:21]([C:19]([N:10]2[C:11]3[CH:18]=[CH:17][CH:16]=[CH:15][C:12]=3[CH2:13][N:14]3[C:5]([C:3]([NH:43][CH2:42][C:41]4[CH:44]=[CH:45][CH:46]=[CH:47][C:40]=4[C:39]([F:48])([F:49])[F:38])=[O:4])=[CH:6][CH:7]=[C:8]3[CH2:9]2)=[O:20])[CH:26]=[CH:25][C:24]=1[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[CH3:33]
Reactant: NCc1ccccc1C(F)(F)F
Reactant: COc1cc(C(=O)N2Cc3ccc(C(=O)C(Cl)(Cl)Cl)n3Cc3ccccc32)ccc1-c1ccccc1C
Product: COc1cc(C(=O)N2Cc3ccc(C(=O)NCc4ccccc4C(F)(F)F)n3Cc3ccccc32)ccc1-c1ccccc1C
Yield: 75 %

Procedure:
The title compound was prepared in 75% yield in the manner of Example 36 from 2,2,2-trichloro-1-{10-[(2-methoxy-2′-methyl-1,1′-biphenyl-4-yl)carbonyl]-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl}ethanone of Example 35 and 2-trifluoromethylbenzylamine, m.p. 165-167° C. MS [(+)ESI, m/z]: 610 [M+H]+ Anal. Calcd for C36H30F3N3O3: C, 70.93; H, 4.96; N, 6.89. Found: C, 70.70; H, 4.89; N, 6.81.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([C:11]([OH:13])=O)[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:14][C:15]1[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][N:16]=1.O>N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[C:1]([O:5][C:6]([NH:8][C@H:9]([C:11]([NH:14][C:15]1[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][N:16]=1)=[O:13])[CH3:10])=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: Nc1ccc(Br)cn1
Reactant: C[C@H](NC(=O)OC(C)(C)C)C(=O)O
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Solvent: O
Product: C[C@H](NC(=O)OC(C)(C)C)C(=O)Nc1ccc(Br)cn1
Temperature: 25 °C
Reaction time: 15 h
Yield: 35.8 %

Procedure:
In 20 ml of pyridine was dissolved 2.19 g of N-t-butoxycarbonyl-L-alanine and the solution was added with 1 g of 2-amino-5-bromopyridine, 2.77 g of 1-(3-dimethyl(aminopropyl)-3-ethylcarbodimide hydrochloride and 1.41 g of 4-dimethylaminopyridine individually and stirred at room temperature for 15 hours. Water was then added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer thus separated was washed with brine, dehydrated, filtered, and concentrated in vacuo to give 0.713 g of 2-(N-t-butoxycarbonyl-L-alanylamino)-5-bromopyridine. This compound was dissolved, along with 0.714 g of (S)-[N-3-(4-trimethylstannyl-3-fluorophenyl)-2-oxo-5-oxazolidinyl]methyl acetamide, in 20 ml of dimethylformamide. Reaction was conducted at 100° C. for 4 hours in the presence of 0.6 ml of triethyl amine with the catalytic aid of 0.36 g of dichlorobistriphenylphosphine palladium (II) with stirring after their addition at room temperature. Water was then added to the reaction mixture, followed by the extraction with ethyl acetate. The organic layer thus separated was washed with brine, dehydrated, filtered and concentrated in vacuo. Recrystallization of the concentrate gave 0.27 g of (S)-[N-3-(4-(2-(N-t-buxotycarbonyl-L-alanylaminopyridin-5-yl)-3-fluorophenyl)-2-oxo-5-oxazolidinyl)methyl acetamide. This compound was reacted with 0.15 ml of trimethylsilyl iodide in chloroform at room temperature for 30 min under a nitrogen atmosphere. Following the addition of chloroform, the organic layer thus separated was washed with brine, dehydrated, filtered, and concentrated in vacuo. The concentrate was subjected to column chromatography to produce the title compound. 50 mg.
Reaction SMILES: [CH:1]1([C:4]2[N:8]=[C:7]([C:9]3[N:10]=[CH:11][N:12]4[C:21]5[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=5)[NH:15][CH2:14][C:13]=34)[O:6][N:5]=2)[CH2:3][CH2:2]1.[C:22](OC(=O)C)(=[O:24])[CH3:23]>C1COCC1>[C:22]([N:15]1[C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:12]2[CH:11]=[N:10][C:9]([C:7]3[O:6][N:5]=[C:4]([CH:1]4[CH2:3][CH2:2]4)[N:8]=3)=[C:13]2[CH2:14]1)(=[O:24])[CH3:23]
Reactant: c1ccc2c(c1)NCc1c(-c3nc(C4CC4)no3)ncn1-2
Reactant: CC(=O)OC(C)=O
Solvent: C1CCOC1
Product: CC(=O)N1Cc2c(-c3nc(C4CC4)no3)ncn2-c2ccccc21

Procedure:
A mixture of 3-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-4,5-dihydroimidazo[1,5-a]quinoxaline (XXXIII, EXAMPLE 101, 0.201 g) and acetic anhydride (3 ml) in THF (0.7 ml) is heated at 80° for 45 min. The reaction mixture is then cooled, concentrated, and partitioned between dichloromethane and aqueous sodium bicarbonate. The organic phase is separated and filtered through sodium sulfate and concentrated. The crude product is crystallized from dichloromethane and hexane to give the title compound, which is then recrystallized from ethyl ether/ethyl acetate/hexane, mp 202.0°-202.5°; MS (m/z) at 321; IR (mineral oil) 1674, 1639, 1501, 1358 and 1401 cm-1 ; NMR (CDCl3) 1.15, 2.18, 2.29, 5.32, 7.41, 7.62 and 8.15 δ.
Reaction SMILES: [C:1]([C@@H:4]1[CH2:8][C@H:7]([S:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[CH2:6][N:5]1[CH3:19])([OH:3])=O.[OH:20][CH2:21][CH2:22][N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1>C(#N)C>[OH:20][CH2:21][CH2:22][N:23]1[CH2:28][CH2:27][N:26]([C:1]([C@@H:4]2[CH2:8][C@H:7]([S:9][CH2:10][C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)[CH2:6][N:5]2[CH3:19])=[O:3])[CH2:25][CH2:24]1
Reactant: COc1ccc(CS[C@H]2C[C@@H](C(=O)O)N(C)C2)cc1
Reactant: OCCN1CCNCC1
Solvent: CC#N
Product: COc1ccc(CS[C@H]2C[C@@H](C(=O)N3CCN(CCO)CC3)N(C)C2)cc1
Temperature: 40 °C
Reaction time: 0.5 h
Yield: 73.4 %

Procedure:
800 mg of N,N'-carbonyldiimidazole were added to a suspension of 1.13 g of (2S,4S)-2-carboxy-4-(4-methoxybenzylthio)-1-methylpyrrolidine in 20 ml of dry acetonitrile, and the resulting mixture was stirred at 40° C. for 30 minutes. At the end of this time, the reaction mixture was ice-cooled, and 600 mg of N-hydroxyethylpiperazine were added to the mixture. The temperature was allowed to rise to room temperature over a period of 30 minutes. The reaction mixture was then concentrated by evaporation under reduced pressure, and the residue was purified by reverse phase column chromatography using LiChroprep RP-8 (trade mark) as the stationary phase and 70% v/v aqueous methanol as the eluent, to give 1160 mg of the title compound as a colorless oil.
Reaction SMILES: [F-].C([N+](CCCC)(CCCC)CCCC)CCC.[CH2:19]([O:26][C:27]([NH:29][CH2:30][C:31]([N:33]([CH2:51][C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[CH2:40][CH2:41][CH2:42][O:43][Si](C(C)(C)C)(C)C)=[O:32])=[O:28])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>C1COCC1.C(OCC)(=O)C>[CH2:19]([O:26][C:27]([NH:29][CH2:30][C:31]([N:33]([CH2:51][C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[CH2:40][CH2:41][CH2:42][OH:43])=[O:32])=[O:28])[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: CC(C)(C)OC(=O)CN(C(=O)CNC(=O)OCc1ccccc1)c1ccccc1CCCO[Si](C)(C)C(C)(C)C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)CN(C(=O)CNC(=O)OCc1ccccc1)c1ccccc1CCCO
Reaction time: 1.5 h

Procedure:
Tetrabutylammonium fluoride (1.0M in THF/10 ml, 10 mmol) was added to a solution of N-(benzyloxycarbonylaminomethylcarbonyl)-N-(tert-butyloxycarbonyl-methyl)-2-(3-tert-butyldimethylsilyloxypropyl)aniline(3.87 g, 6.8 mmol) in THF (25 ml) at room temperature. After stirring for 90 minutes the reaction mixture was diluted with ethyl acetate (150 ml), washed with water (150 ml), brine (150 ml) and dried (MgSO4). Filtration and evaporation of the solvent gave the crude product which was purified by flash chromatography on silica gel with ethyl acetate-hexane (2:1) as eluant (2.39 g, 77%).