Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[S:10][CH2:9][CH2:8][C:7](=[O:11])[C:6]=2[CH:12]=1.CO[CH:15](OC)[N:16]([CH3:18])[CH3:17].C(N(CC)CC)C>C1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[S:10][CH2:9][C:8](=[CH:15][N:16]([CH3:18])[CH3:17])[C:7](=[O:11])[C:6]=2[CH:12]=1
Reactant: COC(OC)N(C)C
Reactant: O=C1CCSc2ccc(Cl)cc21
Solvent: CCN(CC)CC
Solvent: c1ccccc1
Product: CN(C)C=C1CSc2ccc(Cl)cc2C1=O
Reaction time: 1 h

Procedure:
A solution of 6-chloro-2,3-dihydro-4H-1-benzothiopyran-4-one (30 g), N,N-dimethylformamide dimethyl acetal (80 ml), and triethylamine (31.4 ml) in benzene (400 ml) was refluxed with stirring for 1 hour and then about three-fourths of the solvent were distilled slowly at atmospheric pressure over a period of approximately 1 hour. Benzene (300 ml) was added to the reaction mixture and the solvent was distilled again. To the residue was added diethyl ether (150 ml) and the mixture was triturated to give 6-chloro-2,3-dihydro-3-dimethylaminomethylene-4H-1-benzothiopyran-4-one (34 g).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:19])[CH2:11][CH:12]([CH3:18])[CH2:13][C:14]([O:16][CH3:17])=[O:15])=[CH:5][CH:4]=1)#[N:2].[H-].[Na+].[CH2:22](Br)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.O>CN(C=O)C>[CH2:22]([N:9]([C:6]1[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:8][CH:7]=1)[C:10](=[O:19])[CH2:11][CH:12]([CH3:18])[CH2:13][C:14]([O:16][CH3:17])=[O:15])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: COC(=O)CC(C)CC(=O)Nc1ccc(C#N)cc1
Reactant: BrCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)CC(C)CC(=O)N(Cc1ccccc1)c1ccc(C#N)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 26.1 %

Procedure:
To a solution of the compound obtained in Step 1 (228 mg, 0.88 mmol) in DMF (6 mL) was added sodium hydride (60% in oil, 126 mg, 2.63 mmol) at 0° C. The reaction mixture was stirred at room temperature for 30 min, and benzyl bromide (0.156 mL, 1.31 mmol) was added thereto at 0° C. The reaction mixture was stirred at room temperature for 14 hr, to the reaction solution was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 5 to 85% ethyl acetate/hexane) to give methyl 5-(benzyl(4-cyanophenyl)amino)-3-methyl-5-oxopentanoate (81 mg, 0.230 mmol, 26.3%) as a colorless oil.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22]([CH:25]=O)[CH:23]=3)[N:18]=[CH:17][C:16]=2[C:27]#[N:28])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:29]1([NH:32][C:33]2[S:34][CH2:35][C:36](=[O:38])[N:37]=2)[CH2:31][CH2:30]1.C([O-])(=O)C.[Na+]>C(O)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([O:14][C:15]2[C:24]3[C:19](=[CH:20][CH:21]=[C:22](/[CH:25]=[C:35]4/[C:36](=[O:38])[N:37]=[C:33]([NH:32][CH:29]5[CH2:31][CH2:30]5)[S:34]/4)[CH:23]=3)[N:18]=[CH:17][C:16]=2[C:27]#[N:28])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: O=C1CSC(NC2CC2)=N1
Reactant: CC(C)(C)OC(=O)N1CCC(Oc2c(C#N)cnc3ccc(C=O)cc23)CC1
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CC(=O)O
Product: CC(C)(C)OC(=O)N1CCC(Oc2c(C#N)cnc3ccc(/C=C4\SC(NC5CC5)=NC4=O)cc23)CC1

Procedure:
Similar procedure as described in example 28c was used, starting from 4-(3-cyano-6-formyl-quinolin-4-yloxy)-piperidine-1-carboxylic acid tert-butyl ester (example 31b), 2-cyclopropylamino-thiazol-4-one, sodium acetate and acetic acid to give 4-{3-cyano-6-[2-cyclopropylamino-4-oxo-4H-thiazol-(5Z)-ylidenemethyl]-quinolin-4-yloxy}-piperidine-1-carboxylic acid tert-butyl ester. LC-MS m/e 520 (MH+).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[OH:9].C(N(CC)CC)C.Cl[C:18]([O:20][CH2:21][CH3:22])=[O:19]>ClCCl>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[O:9][C:18]([O:20][CH2:21][CH3:22])=[O:19]
Reactant: Oc1ccc(F)cc1F
Reactant: CCOC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCOC(=O)Oc1ccc(F)cc1F
Reaction time: 2 h
Yield: 97 %

Procedure:
104 g (796 mmol) of 2,4-difluorophenol was dissolved in 800 ml of dichloromethane, 132 ml of triethylamine and 92.0 ml of ethyl chloroformate were added under ice-cooling and the mixture was stirred at -10° to 0° C. for 2 hours. The reaction solution was washed with an aqueous saturated solution of sodium chloride and dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure to give 156 g (97%) of 2,4-difluoro-O-ethoxycarbonylphenol.
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:14]([C:15]3[CH:24]=[CH:23][C:18]([O:19][CH2:20][CH2:21][NH2:22])=[CH:17][CH:16]=3)[N:13]=[C:12]([C:25]([F:28])([F:27])[F:26])[CH:11]=2)=[CH:6][CH:5]=1.[CH3:29][S:30](Cl)(=[O:32])=[O:31]>ClCCl.C(N(CC)CC)C>[CH3:2][O:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]2[N:14]([C:15]3[CH:24]=[CH:23][C:18]([O:19][CH2:20][CH2:21][NH:22][S:30]([CH3:29])(=[O:32])=[O:31])=[CH:17][CH:16]=3)[N:13]=[C:12]([C:25]([F:28])([F:26])[F:27])[CH:11]=2)=[CH:8][CH:9]=1
Reactant: CS(=O)(=O)Cl
Reactant: COc1ccc(-c2cc(C(F)(F)F)nn2-c2ccc(OCCN)cc2)cc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1ccc(-c2cc(C(F)(F)F)nn2-c2ccc(OCCNS(C)(=O)=O)cc2)cc1

Procedure:
To a solution of 2-{4-[5-(4-methoxyphenyl)-3-(trifluoromethyl)-1-H-pyrazol-1-yl]phenoxy}ethanamine hydrochloride obtained by Example 96 (100 mg) in dichloromethane (5 ml) and triethylamine (0.1 ml) was added dropwise methanesulfonyl chloride (38 μl) at room temperature.
Reaction SMILES: Cl.[NH2:2][C@H:3]([C:7]([OH:9])=[O:8])[CH:4]([CH3:6])[CH3:5].Cl[CH2:11]Cl>>[CH3:11][O:8][C:7](=[O:9])[C@H:3]([CH:4]([CH3:6])[CH3:5])[NH2:2]
Reactant: ClCCl
Reactant: CC(C)[C@H](N)C(=O)O
Agent: Cl
Product: COC(=O)[C@@H](N)C(C)C
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
500 mg of methyl ester of L-(+)-valine hydrochloride are placed in a round-bottom flask. 45 mL of buffer solution (K2HPO4/K3PO4 (pH=12.4)), then 22.5 mL of anhydrous dichloromethane are successively added. The mixture is agitated at room temperature for 30 min. The organic phase is separated, washed with brine, dried on magnesium sulfate, filtered and concentrated under vacuum.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][C@@H:6]([NH:11][C:12]([C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][C@@H:22]3[CH2:26][CH2:25][CH2:24][O:23]3)=[CH:16][N:15]=1)=[O:13])[CH2:5]2.[CH2:27](C([Sn])=C(CCCC)CCCC)[CH2:28]CC.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CN(C=O)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(N(CC)CC)C>[CH:27]([C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][C@@H:6]([NH:11][C:12]([C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][C@@H:22]3[CH2:26][CH2:25][CH2:24][O:23]3)=[CH:16][N:15]=1)=[O:13])[CH2:5]2)=[CH2:28]
Reactant: O=C(N[C@@H]1Cc2ccc(Br)cc2C1)c1ccc(OC[C@@H]2CCCO2)cn1
Reactant: CCCCC([Sn])=C(CCCC)CCCC
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: C=Cc1ccc2c(c1)C[C@H](NC(=O)c1ccc(OC[C@@H]3CCCO3)cn1)C2

Procedure:
A mixture of N-((R)-5-bromoindan-2-yl)-5-[(S)-1-(tetrahydrofuran-2-yl)methoxy]pyridine-2-carboxamide (1.70 g), tributylvinyltin (1.55 g), triphenylphosphine (85.5 mg), palladium(II) acetate (18.3 mg) and DMF (20 ml) was admixed under argon with triethylamine (7.4 ml) and heated to reflux for 4 hours. After cooling, the reaction mixture was partitioned between water and ethyl acetate. The organic phase was dried over sodium sulfate and concentrated. The residue was filtered through silica gel. This afforded the product with the molecular weight of 364.45 (C22H24N2O3); MS (ESI): 365 (M+H+).
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:9]=[C:8]([N+:10]([O-])=O)[CH:7]=[CH:6][C:5]=1[O:13][CH3:14])[CH3:2].[H][H]>C(OCC)(=O)C.[Pd]>[CH2:1]([O:3][C:4]1[CH:9]=[C:8]([NH2:10])[CH:7]=[CH:6][C:5]=1[O:13][CH3:14])[CH3:2]
Reactant: [H][H]
Reactant: CCOc1cc([N+](=O)[O-])ccc1OC
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CCOc1cc(N)ccc1OC
Yield: 98.4 %

Procedure:
A mixture of 2-ethoxy-1-methoxy-4-nitrobenzene (1.5 g, 7.6 mmol) and 5% Pd—C (0.3 g) in 30 mL of ethyl acetate was hydrogenated under 50 psi of hydrogen gas for 14 hours. The mixture was filtered through Celite and the filtrate was evaporated, providing 1.25 g of the product, in 98% yield: 1H NMR (CDCl3) δ 1.44 (t, J=7.0 Hz, 3H), 3.27 (br, 2H), 3.79 (s, 3H), 4.04 (q, J=7.0 Hz, 2H), 6.90 (d, J=8.9 Hz, 1H), 7.74 (d, J=2.5 Hz, 1H), 7.90 (dd, J=8.9 Hz, J=2.5 Hz, 1H).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:26])[CH:4]([C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[C:11]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:10]=1)[C:5]([O:7][CH3:8])=[O:6].[CH3:27]N1CCCC1=O.[H-].[Na+].IC>O>[CH3:8][O:7][C:5](=[O:6])[C:4]([C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[C:11]([O:18][CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH:10]=1)([CH3:27])[C:3]([O:2][CH3:1])=[O:26]
Reactant: CN1CCCC1=O
Reactant: COC(=O)C(C(=O)OC)c1ccc([N+](=O)[O-])c(OCc2ccccc2)c1
Agent: [H-]
Agent: [Na+]
Solvent: CI
Solvent: O
Product: COC(=O)C(C)(C(=O)OC)c1ccc([N+](=O)[O-])c(OCc2ccccc2)c1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A mixture of dimethyl-(3-benzyloxy-4-nitrophenyl)malonate(2.3 g), N-methylpyrrolidinone(15 mL) and a 60% dispersion of sodium hydride in mineral oil(0.31 g) was stirred under an argon atmosphere at 0° C. for 0.5 h. The mixture was treated with iodomethane(0.8 mL) and stirred at ambient temperature for 4 h then treated with water (50 mL). The precipitate was collected and washed with water and hexane to give dimethyl-2-(3-benzyloxy-4-nitrophenyl)-2-methylmalonate(2.19 g). [m/e374(MH+)].
Reaction SMILES: [O:1]1[CH2:6][CH2:5][C:4](=[O:7])[CH2:3][CH2:2]1.Cl[CH2:9][C:10]#[N:11].CC(C)([O-])C.[K+]>C(O)(C)(C)C.O.Cl>[O:7]1[C:4]2([CH2:5][CH2:6][O:1][CH2:2][CH2:3]2)[CH:9]1[C:10]#[N:11]
Reactant: N#CCCl
Reactant: O=C1CCOCC1
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: O
Solvent: CC(C)(C)O
Product: N#CC1OC12CCOCC2
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A mixture of dihydro-2H-pyran-4(3H)-one (10.0 g) and 2-chloroacetonitrile (7.5 g) in tert-butanol (10 mL) was treated with 1.0 N potassium tert-butoxide (100 mL) drop-wise over 20 minutes. The reaction mixture was stirred at room temperature for 16 hours. It was diluted with water (10 mL) and 10% aqueous HCl (20 mL). The reaction mixture was concentrated to one-third of its original volume, and extracted with diethyl ether four times. The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified with flash column chromatography on silica gel eluting with 20-40% ethyl acetate in hexanes.
Reaction SMILES: [F:1][C:2]([F:31])([F:30])[O:3][C:4]1[CH:29]=[CH:28][C:7]([CH2:8][C@:9]23[CH2:16][C@H:15]([NH2:17])[CH2:14][N:13]2[C:12](=[O:18])[N:11]([C:19]2[CH:24]=[C:23]([Cl:25])[N:22]=[C:21]([Cl:26])[CH:20]=2)[C:10]3=[O:27])=[CH:6][CH:5]=1.C([O-])(=O)C.[Na+].CO[C:39]1O[C:41](OC)=[CH:42][CH:43]=1.C([O-])(O)=O.[Na+]>C(O)(=O)C.CCOC(C)=O>[F:31][C:2]([F:30])([F:1])[O:3][C:4]1[CH:29]=[CH:28][C:7]([CH2:8][C@:9]23[CH2:16][C@H:15]([N:17]4[CH:39]=[CH:43][CH:42]=[CH:41]4)[CH2:14][N:13]2[C:12](=[O:18])[N:11]([C:19]2[CH:24]=[C:23]([Cl:25])[N:22]=[C:21]([Cl:26])[CH:20]=2)[C:10]3=[O:27])=[CH:6][CH:5]=1
Reactant: COc1ccc(OC)o1
Reactant: N[C@@H]1CN2C(=O)N(c3cc(Cl)nc(Cl)c3)C(=O)[C@@]2(Cc2ccc(OC(F)(F)F)cc2)C1
Agent: CC(=O)[O-]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: O=C1N(c2cc(Cl)nc(Cl)c2)C(=O)[C@@]2(Cc3ccc(OC(F)(F)F)cc3)C[C@H](n3cccc3)CN12

Procedure:
To a solution of the compound from Example 63 (0.25 g) in acetic acid (5 mL) was added sodium acetate (0.26 g) and 2,5-dimethoxyfuran (0.14 mL). After 20 minutes at reflux, the reaction was cooled, diluted with EtOAc, neutralized with solid NaHCO3. The organic solution was collected, washed with saturated NaHCO3 and brine, dried (Na2SO4), filtered, concentrated and purified by chromatography (silica gel; 95:5 CH2Cl2/methanol, Chromatotron) to afford the titled compound (0.145 g): MS (m/z) 525 [MH+]. mp 129.5° C.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][C:7](B(O)O)=[CH:6][CH:5]=1)([OH:3])=[O:2].Br[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH:21]([F:23])[F:22])=[CH:16][N:15]=1>>[F:22][CH:21]([F:23])[O:20][C:17]1[CH:18]=[CH:19][C:14]([C:7]2[CH:8]=[CH:9][C:4]([C:1]([OH:3])=[O:2])=[CH:5][CH:6]=2)=[N:15][CH:16]=1
Reactant: FC(F)Oc1ccc(Br)nc1
Reactant: O=C(O)c1ccc(B(O)O)cc1
Product: O=C(O)c1ccc(-c2ccc(OC(F)F)cn2)cc1

Procedure:
Operations similar to those of Production Example 14 were conducted using 4-carboxyphenylboronic acid and 2-bromo-5-(difluoromethoxy)pyridine, to provide the title compound as white solid.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([OH:15])[CH:13]=2)[N:8]([C:16]2[CH:21]=[CH:20][C:19]([CH2:22][C:23]([OH:25])=[O:24])=[CH:18][CH:17]=2)[C:7]=1[CH2:26][C:27]([OH:29])=[O:28])=[O:5])[CH3:2].[F:30][C:31]([F:42])([F:41])[C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1>>[CH2:1]([O:3][C:4]([C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[C:12]([O:15][C:35]3[CH:36]=[CH:37][C:32]([C:31]([F:42])([F:41])[F:30])=[CH:33][CH:34]=3)[CH:13]=2)[N:8]([C:16]2[CH:21]=[CH:20][C:19]([CH2:22][C:23]([OH:25])=[O:24])=[CH:18][CH:17]=2)[C:7]=1[CH2:26][C:27]([OH:29])=[O:28])=[O:5])[CH3:2]
Reactant: OB(O)c1ccc(C(F)(F)F)cc1
Reactant: CCOC(=O)c1c(CC(=O)O)n(-c2ccc(CC(=O)O)cc2)c2ccc(O)cc12
Product: CCOC(=O)c1c(CC(=O)O)n(-c2ccc(CC(=O)O)cc2)c2ccc(Oc3ccc(C(F)(F)F)cc3)cc12

Procedure:
The sub-title compound was prepared in accordance with step (c) Example 1 from 2-carboxymethyl-1-(4-carboxymethyl-phenyl)-5-hydroxyindole-3-carboxylic acid ethyl ester (235 mg, 0.5 mmol, see step (b) Example 7) and 4-trifluoromethylphenylboronic acid (143 mg, 0.75 mmol). Yield 122 mg, 41%.
Reaction SMILES: Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.C([O-])([O-])=O.[Na+].[Na+].[NH2:19][C@H:20]([C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([Br:32])[CH:27]=1)[C@H:21]([OH:25])[C:22]([OH:24])=[O:23].O1CCOCC1>O>[Br:32][C:28]1[CH:27]=[C:26]([C@@H:20]2[C@@H:21]([C:22]([OH:24])=[O:23])[O:25][C:2](=[O:4])[NH:19]2)[CH:31]=[CH:30][CH:29]=1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: N[C@H](c1cccc(Br)c1)[C@H](O)C(=O)O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: O=C1N[C@H](c2cccc(Br)c2)[C@@H](C(=O)O)O1
Reaction time: 0.25 h
Yield: 61 %

Procedure:
To triphosgene (36.5 mg, 0.123 mmol) and Na2CO3 (65.2 mg, 0.615 mmol) in Water (2.000 mL) at 0° C. was added dropwise a solution of (2S,3R)-3-amino-3-(3-bromophenyl)-2-hydroxypropanoic acid (20 mg, 0.077 mmol) in Water (0.5 mL)/1,4-Dioxane (0.5 mL). After 15 min, the ice bath was removed and stirring was continued for one hour. ethylacetate (1 ml) was added to the reaction mixture and after five minutes the ethylacetate layer was discarded and the aqueous layer was acidified to pH 2 and extracted with ethylacetate (5 mL×3). The combined organics were dried over magnesium sulfate, filtered and concentrated providing (4R,5S)-4-(3-bromophenyl)-2-oxooxazolidine-5-carboxylic acid (14.2 mg, 0.047 mmol, 61.3% yield) as a white solid. Mass spec.: 287.79 (MH)+.
Reaction SMILES: NCC(N)C.[C:6]1([CH:12]([NH2:15])[CH2:13][NH2:14])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[C:16]([NH:24][C:25]1[CH:26]=[C:27]([CH:31]=[CH:32][N:33]=1)[C:28](O)=O)(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>>[C:6]1([CH:12]2[CH2:13][NH:14][C:28]([C:27]3[CH:31]=[CH:32][N:33]=[C:25]([NH:24][C:16](=[O:23])[C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=4)[CH:26]=3)=[N:15]2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: O=C(O)c1ccnc(NC(=O)c2ccccc2)c1
Reactant: NCC(N)c1ccccc1
Agent: CC(N)CN
Product: O=C(Nc1cc(C2=NC(c3ccccc3)CN2)ccn1)c1ccccc1
Yield: 17 %

Procedure:
Following the procedure as described in Example 9, making variations as required to replace 1,2-diaminopropane with 1-phenylethane-1,2-diamine to react with 2-benzamidoisonicotinic acid, N-(4-(4-phenyl-4,5-dihydro-1H-imidazol-2-yl)pyridin-2-yl)benzamide was obtained in 17% yield: MS (ES+) m/z 343.3 (M+1).
Reaction SMILES: [CH2:1]([CH:5]([CH:9]=[CH2:10])[C:6](=[O:8])[CH3:7])[CH2:2][CH2:3][CH3:4].ClC1C=CC=C(C(OO)=[O:19])C=1.O>ClCCl>[CH2:1]([CH:5]([CH:9]1[O:19][CH2:10]1)[C:6](=[O:8])[CH3:7])[CH2:2][CH2:3][CH3:4]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: C=CC(CCCC)C(C)=O
Solvent: O
Solvent: ClCCl
Product: CCCCC(C(C)=O)C1CO1
Reaction time: 1 h
Yield: 85.3 %

Procedure:
To a solution of 3-butyl-4-penten-2-one (14.0 g) in dichloromethane (100 ml) was added m-chloroperbenzoic acid (26.0 g) at 0° to 5° C., and the mixture was stirred at the same temperature for 1 hour and then at 20° C. for 12 hours. The reaction solution was then poured into water, followed by phase separation. The dichloromethane layer was washed with an aqueous sodium hydrogen carbonate solution and then with an aqueous sodium sulfite solution, followed by concentrating. The residue was distilled to obtain 13.3 g of 3-butyl-4,5-epoxy-pentan-2-one.
Reaction SMILES: [C:1]([O:6][C@@H:7]1[C@@H:15]([CH2:16][CH2:17][OH:18])[C:14](=[O:19])[O:13][CH2:12][C@H:11]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C:10](=[O:28])[O:9][C@H:8]1[CH3:29])(=[O:5])[CH:2]([CH3:4])[CH3:3].N1C=CC=CC=1.[CH3:36][S:37](Cl)(=[O:39])=[O:38]>C(Cl)Cl>[C:1]([O:6][C@@H:7]1[C@@H:15]([CH2:16][CH2:17][O:18][S:37]([CH3:36])(=[O:39])=[O:38])[C:14](=[O:19])[O:13][CH2:12][C@H:11]([NH:20][C:21]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:22])[C:10](=[O:28])[O:9][C@H:8]1[CH3:29])(=[O:5])[CH:2]([CH3:4])[CH3:3]
Reactant: CC(C)C(=O)O[C@H]1[C@H](C)OC(=O)[C@@H](NC(=O)OC(C)(C)C)COC(=O)[C@@H]1CCO
Reactant: CS(=O)(=O)Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(C)C(=O)O[C@H]1[C@H](C)OC(=O)[C@@H](NC(=O)OC(C)(C)C)COC(=O)[C@@H]1CCOS(C)(=O)=O
Temperature: 22 °C
Reaction time: 8 h
Yield: 84.3 %

Procedure:
To a solution of (3S,6S,7R,8R)-3-(tert-butoxycarbonylamino)-8-(2-hydroxyethyl)-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl isobutyrate (660 mg, 1.58 mmol) in CH2Cl2 (15 mL) at 0° C. was added pyridine (750 mg, 9.48 mmol), followed by methanesulfonyl chloride (362 mg, 3.16 mmol). The resulting reaction mixture was warmed up to room temperature (about 22° C.) and stirred overnight. The reaction mixture was partitioned between sat'd aqueous NaHCO3 solution (30 mL) and EtOAc (40 mL) and the phases were separated. The aqueous phase was extracted with additional EtOAc (2×30 mL) and the combined EtOAc extracts were dried over Na2SO4, filtered, and concentrated to dryness. The crude residue was purified via column chromatography (SiO2, hexanes/EtOAc gradient) to afford the title compound (660 mg, 84%) as a white solid: 1H NMR (300 MHz, CDCl3) δ 5.24 (s, 2H), 5.06 (t, J=9.8 Hz, 1H), 4.95-4.77 (m, 2H), 4.32-4.19 (m, 1H), 4.13-4.05 (m, 1H), 3.62 (s, 1H), 2.98 (s, 3H), 2.78 (dd, J=14.9, 6.4 Hz, 1H), 2.62 (dt, J=13.9, 7.0 Hz, 1H), 2.25-2.08 (m, 1H), 1.83 (s, 1H), 1.47 (d, J=11.9 Hz, 9H), 1.28 (d, J=6.3 Hz, 3H), 1.21 (d, J=6.9 Hz, 6H); ESIMS m/z 496 ([M+H]+).
Reaction SMILES: [Cl:1][C:2]1[N:3]([CH2:10][C:11]2([CH3:14])[CH2:13][O:12]2)[CH:4]=[C:5]([N+:7]([O-:9])=[O:8])[N:6]=1.[NH:15]1[CH2:20][CH2:19][CH:18]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:31])[F:30])=[CH:24][CH:23]=2)[CH2:17][CH2:16]1.O>CN(C=O)C>[Cl:1][C:2]1[N:3]([CH2:10][C:11]([CH3:14])([OH:12])[CH2:13][N:15]2[CH2:20][CH2:19][CH:18]([NH:21][C:22]3[CH:23]=[CH:24][C:25]([O:28][C:29]([F:30])([F:31])[F:32])=[CH:26][CH:27]=3)[CH2:17][CH2:16]2)[CH:4]=[C:5]([N+:7]([O-:9])=[O:8])[N:6]=1
Reactant: CC1(Cn2cc([N+](=O)[O-])nc2Cl)CO1
Reactant: FC(F)(F)Oc1ccc(NC2CCNCC2)cc1
Solvent: O
Solvent: CN(C)C=O
Product: CC(O)(CN1CCC(Nc2ccc(OC(F)(F)F)cc2)CC1)Cn1cc([N+](=O)[O-])nc1Cl
Yield: 56.1 %

Procedure:
A solution of 2-chloro-1-(2-methyloxiran-2-ylmethyl)-4-nitroimidazole prepared in Example 6 (0.3 g, 1.38 mmol) and N-(piperidin-4-yl)-4-trifluoromethoxyaniline (0.43 g, 1.66 mmol) in DMF (8 ml) was stirred at 80° C. for 2 hours. To the reaction mixture, water was added, and the solution was extracted with ethyl acetate, dried over magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=1/1) to afford 1-(2-chloro-4-nitroimidazol-1-yl)-2-methyl-3-[4-(4-trifluoromethoxyphenylamino)piperidin-1-yl]propan-2-ol (0.37 g, yield 56%) as a yellow oil.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.[N+:7]([C:10]1[CH:20]=[CH:19][C:13]([CH2:14][P:15](=[O:18])([OH:17])[OH:16])=[CH:12][CH:11]=1)([O-:9])=[O:8].N1C=C[CH:24]=[CH:23][CH:22]=1>O1CCCC1>[N+:7]([C:10]1[CH:20]=[CH:19][C:13]([CH2:14][P:15]2(=[O:16])[O:17][CH2:24][CH2:23][CH2:22][O:18]2)=[CH:12][CH:11]=1)([O-:9])=[O:8]
Reactant: c1ccncc1
Reactant: O=[N+]([O-])c1ccc(CP(=O)(O)O)cc1
Agent: O=C(Cl)C(=O)Cl
Solvent: C1CCOC1
Product: O=[N+]([O-])c1ccc(CP2(=O)OCCCO2)cc1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 26.4 %

Procedure:
Oxalyl chloride (22.09 g) was added dropwise to a mixture of 4-nitrobenzylphosphonic acid (17.99 g), pyridine (13.76 g) and tetrahydrofuran (500 ml) at -78° C. After the mixture was stirred at -78° C. for 30 minutes and then at room temperature for 1.5 hours, the insoluble solid was filtered off. The filtrate was concentrated under reduced pressure, and the residual oily substance was dissolved in tetrahydrofuran (500 ml). To this solution, a solution of 1,3-propanediol (2.58 g) in acetonitrile (30 ml) was added dropwise at -78° C. over a 15-minute period. Then, pyridine (5.62 g) was added dropwise at -78° C. over a 5-minute period, and the mixture was stirred at room temperature for 15 hours. After the insoluble solid was filtered off, the filtrate was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate-chloroform-methanol (10:10:1, v/v) to yield 2-(4-nitrobenzyl)-1,3,2-dioxaphosphorinane-2-oxide (5.62 g, 26%), which was then recrystallized from ethanol-hexane to yield colorless needles having a melting point of 144° to 145° C.
Reaction SMILES: C[SiH:2]([CH2:13]CCCCCCCCC)[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[CH2:23]=[CH:24][CH2:25]CCCCCCC>C1C=CC=CC=1.[C-]#[O+].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Rh]>[CH3:13][SiH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:23][CH2:24][CH3:25]
Reactant: C=CCCCCCCCC
Reactant: CCCCCCCCCC[SiH](C)CCCCCCCCCC
Agent: [Rh]
Agent: [C-]#[O+]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: c1ccccc1
Product: CCCCCCCCCCCCC[SiH2]C
Yield: 85 %

Procedure:
A mixture of 1.53 grams of methyldidecylsilane, and 0.70 gram of 1-decene in 5 milliliters of benzene was reacted for 25 hours at 50° C. in the presence of 0.005 gram hydridocarbonyltris(triphenylphosphine)rhodium(I). Chromatographic analysis showed that an 85 percent yield of methyltridecylsilane was formed at a 65 percent silane conversion.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[F:7][C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[C:10]([NH:22][C:23]2[N:28]=[C:27](SC#N)[C:26]([N+:32]([O-:34])=[O:33])=[CH:25][N:24]=2)[CH:9]=1.[OH:35][C@H:36]1[CH2:41][CH2:40][C@H:39]([NH2:42])[CH2:38][CH2:37]1>C(#N)C.C(Cl)Cl>[F:7][C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:19])([CH3:18])[CH3:20])=[C:10]([NH:22][C:23]2[N:28]=[C:27]([NH:42][C@H:39]3[CH2:40][CH2:41][C@H:36]([OH:35])[CH2:37][CH2:38]3)[C:26]([N+:32]([O-:34])=[O:33])=[CH:25][N:24]=2)[CH:9]=1
Reactant: N[C@H]1CC[C@H](O)CC1
Reactant: CC(C)(C)OC(=O)Nc1ccc(F)cc1Nc1ncc([N+](=O)[O-])c(SC#N)n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: CC#N
Product: CC(C)(C)OC(=O)Nc1ccc(F)cc1Nc1ncc([N+](=O)[O-])c(N[C@H]2CC[C@H](O)CC2)n1
Reaction time: 16 h

Procedure:
Potassium carbonate (105 mg) was added to a stirred mixture of tert-butyl 4-fluoro-2-(5-nitro-4-thiocyanatopyrimidin-2-ylamino)phenyl-carbamate (101 mg) in acetonitrile (5 ml) followed by the addition of trans-4-hydroxycyclohexylamine (44 mg). The reaction mixture was stirred for 16 hours, then diluted with DCM and washed with water and brine. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo to provide 110 mg of the title compound.