Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N:1]([O-:3])=O.[Na+].[CH:5](=[C:12]1[NH:16][C:15](=[O:17])[CH:14]=[C:13]1[OH:18])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1>C(O)(=O)C>[CH:5](=[C:12]1[NH:16][C:15](=[O:17])[CH2:14][C:13]1([OH:18])[N:1]=[O:3])[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1
Reactant: O=N[O-]
Reactant: O=C1C=C(O)C(=Cc2ccccc2)N1
Agent: [Na+]
Solvent: CC(=O)O
Product: O=NC1(O)CC(=O)NC1=Cc1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 65 %

Procedure:
An aqueous solution of sodium nitrite (0.075 g, 1.1 mmol) was added to an ice-cooled suspension of 2 mmol (0.432 g) 5-benzylidene-4-hydroxy-1,5-dihydro-pyrrol-2-one (prepared by the method of H. Poschenrieder et al (Arch. Pharm. Pharm. Med. Chem. 1998, vol. 331, pp. 389-394) and Stachel et al (J. Heterocycl. Chem. 1980, vol. 17, pp. 1195-1199 and Liebigs Ann. Chem. 1985, pp. 1692-1696)) in 5 ml glacial acetic acid, while stirring, and the mixture was stirred at room temperature for 30 minutes. The reaction solution was concentrated and orange crystals of 5-benzylidene-4-hydroxy-4-nitroso-1,5-dihydro-pyrrol-2-one were obtained in a yield of 65% by recrystallization from ethanol. The substance decomposes at 205° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:22]2[CH:27]=[CH:26][C:25]([C:28]([OH:30])=O)=[CH:24][CH:23]=2)[CH:5]=[C:6]([Cl:21])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([N:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)[C:10]1=[O:20].C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[F:44][C:45]([F:53])([F:52])[CH:46]1[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C:22]2[CH:23]=[CH:24][C:25]([C:28]([N:49]3[CH2:50][CH2:51][CH:46]([C:45]([F:53])([F:52])[F:44])[CH2:47][CH2:48]3)=[O:30])=[CH:26][CH:27]=2)[CH:5]=[C:6]([Cl:21])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([N:14]2[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]2)[C:10]1=[O:20]
Reactant: O=C(O)c1ccc(-c2cc(Cl)c(C[C@@H]3CCN(N4CCCCC4)C3=O)c(Cl)c2)cc1
Reactant: FC(F)(F)C1CCNCC1
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: O=C(c1ccc(-c2cc(Cl)c(C[C@@H]3CCN(N4CCCCC4)C3=O)c(Cl)c2)cc1)N1CCC(C(F)(F)F)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 55.8 %

Procedure:
Treat a solution of (R)-3′,5′-dichloro-4′-(2-oxo-1-piperidin-1-yl-pyrrolidin-3-ylmethyl)-biphenyl-4-carboxylic acid (0.090 g, 0.2 mmol) in CH2Cl2 (10 mL) with 1,1′-carbonyldiimidazole (0.065 g, 0.4 mmol) and stir for 1 hour at room temperature. Treat the reaction with 4-trifluoromethylpiperidine hydrochloride (0.057 g, 0.3 mmol) and diisopropylethylamine (0.039 g, 0.3 mmol) and stir for 12 hours at room temperature. Purify on silica gel column with 25% to 75% ethyl acetate in hexanes to afford 0.065 g (55%) of the title compound. MS (m/z): 582 (M+).
Reaction SMILES: [OH:1]O.[CH2:3]([S:5][C:6]([CH2:11][CH3:12])=[CH:7][N+:8]([O-:10])=[O:9])[CH3:4]>C(O)=O>[CH2:3]([S:5]([C:6]([CH2:11][CH3:12])=[CH:7][N+:8]([O-:10])=[O:9])=[O:1])[CH3:4]
Reactant: CCSC(=C[N+](=O)[O-])CC
Reactant: OO
Solvent: O=CO
Product: CCC(=C[N+](=O)[O-])S(=O)CC
Temperature: 25 °C
Reaction time: 18 h
Yield: 25 %

Procedure:
2-Ethylsulfinyl-1-nitrobutene was prepared by the dropwise addition of aqueous hydrogen peroxide (1.05 g., 0.0093 mol) to a stirred solution of 2-ethylthio-1-nitrobutene (1.50 g., 0.0093 mol) in formic acid (20 ml.). The resulting solution was stirred at room temperature for 18 hours. The solvent was removed under reduced pressure and the residue was dissolved in methylene chloride, washed successively with saturated aqueous sodium bicarbonate (1×50 ml.) and deionized water (1×50 ml.), dried over anhydrous magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (2:1 hexanes/ethyl acetate) afforded the isomeric mixture of the product as a yellow oil, 0.42g., 25% yield. 1H-NMR (CDCl3): δ 1.26, m, 3H, CH3 ; 1.5, t, 3H, CH3 ; 2.5-2.85, m, 2H, --CH2 --; 2.85-3.2, m, 2H, SCH2 --; 7.2+7.3, 2s, 1H, olefinic H.
Reaction SMILES: [F:1][C:2]1[CH:9]=[N:8][CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].C(O)C.[BH4-].[Na+]>O>[F:1][C:2]1[CH:9]=[N:8][CH:7]=[CH:6][C:3]=1[CH2:4][OH:5]
Reactant: O=Cc1ccncc1F
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: OCc1ccncc1F
Yield: 91.9 %

Procedure:
To a mixture of 1.2 g of 3-fluoroisonicotinaldehyde and 5 ml of ethanol was gradually added 0.36 g of sodium borohydride under ice-cooling, and the mixture was stirred under ice-cooling for 3 hours. Water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The organic layers were combined and washed with saturated brine and dried over magnesium sulfate. The resulting mixture was concentrated under reduced pressure to obtain 1.12 g of (3-fluoropyridin-4-yl)methanol.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[C:8]([CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N+:18]([O-])=O)[CH:7]=[C:6]([CH:21]([CH3:23])[CH3:22])[C:5]=1[OH:24])([CH3:3])[CH3:2]>C(O)C.[C].[Pd]>[NH2:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[CH2:11][CH2:10][C:8]1[CH:9]=[C:4]([CH:1]([CH3:2])[CH3:3])[C:5]([OH:24])=[C:6]([CH:21]([CH3:22])[CH3:23])[CH:7]=1
Reactant: CC(C)c1cc(C=Cc2ccccc2[N+](=O)[O-])cc(C(C)C)c1O
Agent: [Pd]
Solvent: CCO
Product: CC(C)c1cc(CCc2ccccc2N)cc(C(C)C)c1O
Reaction time: 7 h
Yield: 84.1 %

Procedure:
To a suspension of 2,6-diisopropyl-4-(2nitrostyryl)phenol (1.3 g, 4.0 mmol) in ethanol (20 ml) was added a catalytic amount of 10% palladium carbon and the suspension was subjected to catalytic reduction at 1-2.5 atms at room temperature for 7 hrs. After filtering the catalyst, distilling off the solvent gave 4-(2-aminophenethyl)-2,6-diisopropylphenol (1.0 g, 84%) as a viscous oil.
Reaction SMILES: C([O:4][C@@H:5]1[C@@H:10]([O:11]C(=O)C)[C@H:9]([O:15]C(=O)C)[C@@H:8]([CH2:19][O:20]C(=O)C)[O:7][C@H:6]1[O:24][C:25]1[C:29]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH2:39][C:40]([OH:42])=O)=[CH:33][CH:32]=2)=[C:28]([CH:43]([CH3:45])[CH3:44])[NH:27][N:26]=1)(=O)C.[NH2:46][C@@H:47]([CH3:50])[CH2:48][OH:49].NC(C)(C)C(N)=O>>[C@@H:6]1([O:24][C:25]2[C:29]([CH2:30][C:31]3[CH:32]=[CH:33][C:34]([O:37][CH2:38][CH2:39][C:40](=[O:42])[NH:46][C@@H:47]([CH3:50])[CH2:48][OH:49])=[CH:35][CH:36]=3)=[C:28]([CH:43]([CH3:44])[CH3:45])[NH:27][N:26]=2)[O:7][C@H:8]([CH2:19][OH:20])[C@@H:9]([OH:15])[C@H:10]([OH:11])[C@H:5]1[OH:4]
Reactant: CC(=O)OC[C@H]1O[C@@H](Oc2n[nH]c(C(C)C)c2Cc2ccc(OCCC(=O)O)cc2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: C[C@H](N)CO
Agent: CC(C)(N)C(N)=O
Product: CC(C)c1[nH]nc(O[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)c1Cc1ccc(OCCC(=O)N[C@@H](C)CO)cc1

Procedure:
The title compound was prepared in a similar manner to that described in Example 78 using 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-4-{[4-(2-carboxyethoxy)phenyl]methyl}-5-isopropyl-1H-pyrazole and (S)-2-amino-1-propanol instead of 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-4-{[4-(2-carboxyethoxy)-2-methylphenyl]methyl}-5-isopropyl-1H-pyrazole and 2-amino-2-methylpropionamide, respectively.
Reaction SMILES: [Cl:1][C:2]1[CH:37]=[CH:36][C:5]([C:6]([N:8]2[CH2:14][C:13]3[CH:15]=[CH:16][C:17]([C:19]#[N:20])=[CH:18][C:12]=3[N:11]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([C:28]([N:30]4[CH2:34][CH2:33][CH2:32][CH2:31]4)=[O:29])=[CH:24][CH:23]=3)[C:10](=[O:35])[CH2:9]2)=[O:7])=[CH:4][CH:3]=1.C([Sn]([N:51]=[N+:52]=[N-:53])(CCCC)CCCC)CCC>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:8]2[CH2:14][C:13]3[CH:15]=[CH:16][C:17]([C:19]4[NH:53][N:52]=[N:51][N:20]=4)=[CH:18][C:12]=3[N:11]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([C:28]([N:30]4[CH2:31][CH2:32][CH2:33][CH2:34]4)=[O:29])=[CH:24][CH:23]=3)[C:10](=[O:35])[CH2:9]2)=[O:7])=[CH:36][CH:37]=1
Reactant: CCCC[Sn](CCCC)(CCCC)N=[N+]=[N-]
Reactant: N#Cc1ccc2c(c1)N(Cc1ccc(C(=O)N3CCCC3)cc1)C(=O)CN(C(=O)c1ccc(Cl)cc1)C2
Solvent: Cc1ccccc1
Product: O=C(c1ccc(CN2C(=O)CN(C(=O)c3ccc(Cl)cc3)Cc3ccc(-c4nnn[nH]4)cc32)cc1)N1CCCC1
Temperature: 120 °C
Reaction time: 6 h

Procedure:
30 mg (0.059 mmol) of 4-(4-chlorobenzoyl)-8-cyano-1-[4-(pyrrolidinylcarbonyl)benzyl]-1,3,4,5-tetrahydrobenzo[e][1,4]diazepin-2-on was dissolved in 2 ml of toluene. 0.032 ml (0.11 mmol) of tributyltin azide was added to the obtained solution, and they were stirred at 120° C. for 6 hours. After the treatment with ethyl acetate as the extracting solvent by an ordinary method, the solvent was evaporated and the obtained crude product was treated in the same manner as in Step 3 in Example 1 to obtain the title compound.
Reaction SMILES: [NH2:1][C:2]1[C:3]([F:26])=[CH:4][C:5]([F:25])=[C:6]([N:8]2[C:17]3[C:12](=[CH:13][C:14]([F:20])=[C:15](F)[C:16]=3[Cl:18])[C:11](=[O:21])[C:10]([C:22]([OH:24])=[O:23])=[CH:9]2)[CH:7]=1.[CH2:27]([NH2:30])[CH2:28][NH2:29].C(N(CC)CC)C>C(#N)C>[NH2:29][CH2:28][CH2:27][NH:30][C:15]1[C:16]([Cl:18])=[C:17]2[C:12]([C:11](=[O:21])[C:10]([C:22]([OH:24])=[O:23])=[CH:9][N:8]2[C:6]2[CH:7]=[C:2]([NH2:1])[C:3]([F:26])=[CH:4][C:5]=2[F:25])=[CH:13][C:14]=1[F:20]
Reactant: NCCN
Reactant: Nc1cc(-n2cc(C(=O)O)c(=O)c3cc(F)c(F)c(Cl)c32)c(F)cc1F
Solvent: CCN(CC)CC
Solvent: CC#N
Product: NCCNc1c(F)cc2c(=O)c(C(=O)O)cn(-c3cc(N)c(F)cc3F)c2c1Cl
Yield: 65.2 %

Procedure:
1-(5-Amino-2,4-difluorophenyl)-8-chloro-6,7-difluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (100 mg), ethylenediamine (16 mg) and triethylamine (70 mg) were added to acetonitrile (5 ml), and the mixture was heated under reflux for 2 hours. After the reaction mixture was allowed to cool, deposits were collected by filtration. The deposits were washed successively with ethanol and diethyl ether to obtain the title compound (72 mg) as a pale yellow powder.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([S:16][C:17]([S:24][C:25]2[CH:30]=[C:29]([C:31]([CH3:34])([CH3:33])[CH3:32])[C:28]([OH:35])=[C:27]([C:36]([CH3:39])([CH3:38])[CH3:37])[CH:26]=2)([CH3:23])[CH2:18][CH2:19][C:20]([OH:22])=[O:21])[CH:8]=[C:9]([C:12]([CH3:15])([CH3:14])[CH3:13])[C:10]=1[OH:11])([CH3:4])([CH3:3])[CH3:2]>CCCCCC.ClCCl.[O-2].[O-2].[Mn+4]>[C:20]([CH2:19][CH2:18][C:17]1([CH3:23])[S:24][C:25]2([CH:26]=[C:27]([C:36]([CH3:39])([CH3:38])[CH3:37])[C:28](=[O:35])[C:29]([C:31]([CH3:34])([CH3:33])[CH3:32])=[CH:30]2)[C:7]2([CH:8]=[C:9]([C:12]([CH3:14])([CH3:13])[CH3:15])[C:10](=[O:11])[C:5]([C:1]([CH3:2])([CH3:3])[CH3:4])=[CH:6]2)[S:16]1)([OH:22])=[O:21]
Reactant: CC(CCC(=O)O)(Sc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1)Sc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1
Agent: [Mn+4]
Agent: [O-2]
Solvent: CCCCCC
Solvent: ClCCl
Product: CC1(CCC(=O)O)SC2(C=C(C(C)(C)C)C(=O)C(C(C)(C)C)=C2)C2(C=C(C(C)(C)C)C(=O)C(C(C)(C)C)=C2)S1
Reaction time: 8 h

Procedure:
In a mixture of hexane (10 mL) and dichloromethane (10 mL) was dissolved 4,4-bis(3,5-di-t-butyl-4-hydroxyphenylthio)pentanoic acid (600 mg, 1.04 mmol). Manganese dioxide (600 mg) was added to the resulting solution, and the resulting mixture was stirred overnight. The reaction mixture was filtered by using a celite, and the resulting filtrate was concentrated. The residue obtained by the concentration was purified by a flash column chromatography (filler: manufactured by Kanto Kagaku, K.K., 60Nmesh40-100, developing solvent:n-hexane/ethyl acetate (volume ratio)=1/0 to 2/1) to give an objective compound (yield 355 mg and 59%).
Reaction SMILES: [C:1]([N:9]1[C:17]2[C:12](=[CH:13][C:14]([C:18]([O:20]CC3C=CC=CC=3)=[O:19])=[CH:15][CH:16]=2)[CH:11]=[CH:10]1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H][H]>C(O)C.[Pd]>[C:1]([N:9]1[C:17]2[C:12](=[CH:13][C:14]([C:18]([OH:20])=[O:19])=[CH:15][CH:16]=2)[CH:11]=[CH:10]1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(OCc1ccccc1)c1ccc2c(ccn2C(=O)c2ccccc2)c1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: O=C(O)c1ccc2c(ccn2C(=O)c2ccccc2)c1
Yield: 67 %

Procedure:
The benzyl 1-benzoyl-1H-indole-5-carboxylate (100 mg) obtained above was dissolved in ethanol, and 5% palladium on carbon (20 mg) was added thereto and stirred overnight at room temperature in a hydrogen atmosphere. Insoluble matter was removed by filtration, and the filtrate was concentrated under reduced pressure to give the title compound (50 mg, Y.:66%) as white crystals.
Reaction SMILES: [O:1]([CH2:19][C:20]([CH3:24])([CH3:23])[CH2:21][NH2:22])[Si:2]([C:15]([CH3:18])([CH3:17])[CH3:16])([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl[C:26]([O:28][C:29]1[CH:34]=[CH:33][C:32]([N+:35]([O-:37])=[O:36])=[CH:31][CH:30]=1)=[O:27].C(N(C(C)C)CC)(C)C.C(=O)([O-])O.[Na+]>ClCCl>[O:1]([CH2:19][C:20]([CH3:24])([CH3:23])[CH2:21][NH:22][C:26](=[O:27])[O:28][C:29]1[CH:30]=[CH:31][C:32]([N+:35]([O-:37])=[O:36])=[CH:33][CH:34]=1)[Si:2]([C:15]([CH3:16])([CH3:17])[CH3:18])([C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Reactant: CC(C)(CN)CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(CNC(=O)Oc1ccc([N+](=O)[O-])cc1)CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Reaction time: 0.75 h
Yield: 11.8 %

Procedure:
To a solution, at 0° C., of 0.120 g (3.51 mmol) of 3-(tert-butyldiphenylsilanoxy)-2,2-dimethylpropylamine in 25 ml of dichloromethane are added dropwise 1.42 g (7.03 mmol) of 4-nitrophenyl chloroformate (CAS 7693-46-1) dissolved in 5 ml of dichloromethane. 0.63 ml (3.5 mmol) of diisopropylethylamine is then added. Stirring is continued at 0° C. for 45 minutes, and the temperature of the mixture is then allowed to return to 0° C. over 1 hour. 20 ml of saturated aqueous sodium hydrogen carbonate solution are then added. The organic phase is separated out on a hydrophobic filter cartridge and the solvent is partially evaporated off under reduced pressure to a volume of about 8 ml. This solution is chromatographed on a column of silica gel, eluting with a mixture of 5 to 40% ethyl acetate in cyclohexane, to give 0.21 g of 4-nitrophenyl 3-(tert-butyldiphenylsilanoxy)-2,2-dimethylpropylcarbamate in the form of an oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:10]([C:11]2[S:12][CH:13]=[CH:14][CH:15]=2)=[CH:9][C:6]([CH:7]=O)=[C:5]([O:16][CH2:17][CH2:18][N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)[CH:4]=1.[C:25]([C:28]1[CH:36]=[CH:35][C:31]([C:32]([OH:34])=[O:33])=[CH:30][CH:29]=1)(=[O:27])[CH3:26].C[O-].[Li+].[ClH:40]>CN(C)C=O.CO.O>[ClH:40].[CH3:1][O:2][C:3]1[C:10]([C:11]2[S:12][CH:13]=[CH:14][CH:15]=2)=[CH:9][C:6](/[CH:7]=[CH:26]/[C:25]([C:28]2[CH:36]=[CH:35][C:31]([C:32]([OH:34])=[O:33])=[CH:30][CH:29]=2)=[O:27])=[C:5]([O:16][CH2:17][CH2:18][N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)[CH:4]=1
Reactant: CC(=O)c1ccc(C(=O)O)cc1
Reactant: COc1cc(OCCN2CCOCC2)c(C=O)cc1-c1cccs1
Agent: C[O-]
Agent: Cl
Agent: [Li+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CO
Product: COc1cc(OCCN2CCOCC2)c(/C=C/C(=O)c2ccc(C(=O)O)cc2)cc1-c1cccs1
Temperature: 25 °C
Reaction time: 2 h
Yield: 98 %

Procedure:
4-Methoxy-2-(2-morpholin-4-yl-ethoxy)-5-thiophen-2-yl-benzaldehyde (Ex-60A, 0.15 g, 0.43 mmol) and 4-acetylbenzoic acid (0.071 g, 0.43 mmol) were dissolved in a dimethylformamide-methanol solution (3.0 mL, 7:3). After complete dissolution, lithium methoxide (0.065 g, 1.7 mmol) was added and the resulting bright orange slurry was stirred in the dark at room temperature for 2 h. Upon completion, as determined by HPLC, the mixture was diluted with water (10 mL), acidified with a 1 N hydrochloric acid solution, and extracted with an ethyl acetate:tetrahydrofuran mixture (1:1, 6×20 mL). The combined organic extracts were dried over sodium sulfate and evaporated to dryness. The crude solid was slurried in ethyl alcohol (5 mL) to remove residual impurities and the resulting solid was collected on filter paper and dried in vacuo to yield 0.21 g (98%) of the title compound as a dark yellow solid, mp: 255° C. (dec). 1H-NMR (300 MHz, DMSO-d6) δ 8.34 (s, 1H), 8.26 (d, 2H, J=8.7 Hz), 8.11 (d, 2H, J=8.7 Hz), 8.08 (s, 1H), 7.95 (d, 1H, J=15.9 Hz), 7.71 (d, 1H, J=3.3 Hz), 7.55 (d, 1H, J=4.5 Hz), 7.15 (dd, 1H, J=4.5, 3.3 Hz), 6.94 (s, 1H), 4.68 (brs, 2H), 4.04 (s, 3H), 3.98 (brs, 2H), 3.81–3.88 (brm, 2H), 3.70 (brs, 2H), 3.54–3.58 (brm, 2H), 3.29 (brs, 2H). MS (ESI) m/z=494 ([M+H]+, 100%). Anal. Calcd. for C27H28ClNO6S: C, 61.18; H, 5.32; Cl, 6.69; N, 2.64; S, 6.05. Found: C, 61.18; H, 5.41; Cl, 6.16; N, 2.73; S, 5.87.
Reaction SMILES: [CH:1](O)=[O:2].C(N1C=CN=C1)(N1C=CN=C1)=O.[CH:16]1[N:20]2[C:21]3[C:26]([NH:27][CH2:28][C:19]2=[N:18][C:17]=1[C:29]([O:31][CH2:32][CH3:33])=[O:30])=[CH:25][CH:24]=[CH:23][CH:22]=3.CCOCC>ClCCl>[CH:1]([CH:28]1[NH:27][C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[N:20]2[CH:16]=[C:17]([C:29]([O:31][CH2:32][CH3:33])=[O:30])[N:18]=[C:19]12)=[O:2]
Reactant: O=CO
Reactant: CCOC(=O)c1cn2c(n1)CNc1ccccc1-2
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: ClCCl
Solvent: CCOCC
Product: CCOC(=O)c1cn2c(n1)C(C=O)Nc1ccccc1-2
Temperature: 25 °C
Reaction time: 6 h
Yield: 70.5 %

Procedure:
A solution of 0.70 g of 98% formic acid in 70 ml of dichloromethane was stirred under dry nitrogen with 2.5 g of carbonyldiimidazole for 15 minutes and 1.4 g of ethyl 4,5-dihydroimidazo[1,2-a]quinoxaline-2-carboxylate were added. The mixture was stirred at room temperature for 6 hours under nitrogen and was then poured into ice/aqueous bicarbonate and filtered. The organic layer was dried over magnesium sulfate and evaporated under reduced pressure to a low volume. Dilution with ether gave 1.1 g (70% yield) of ethyl 4-formyl-4,5-dihydroimidazo[1,2-a]quinoxaline-2-carboxylate as colorless crystals after crystallization from dichloromethane/diethyl ether.
Reaction SMILES: C(OC([N:7]1[CH2:11][CH:10]=[C:9]([C:12]2[N:13]=[C:14]([S:17][C:18]3[C@H:24]([CH3:25])[C@H:23]4[N:20]([C:21](=[O:29])[C@@H:22]4[C@H:26]([OH:28])[CH3:27])[C:19]=3[C:30]([O:32]CC=C)=[O:31])[S:15][CH:16]=2)[C@H:8]1[CH2:36][OH:37])=O)C=C.C(O)(=O)C.C([SnH](CCCC)CCCC)CCC.P([O-])([O-])([O-])=O>ClCCl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[OH:28][C@@H:26]([C@H:22]1[C:21](=[O:29])[N:20]2[C@@H:23]1[C@@H:24]([CH3:25])[C:18]([S:17][C:14]1[S:15][CH:16]=[C:12]([C:9]3[C@@H:8]([CH2:36][OH:37])[NH:7][CH2:11][CH:10]=3)[N:13]=1)=[C:19]2[C:30]([OH:32])=[O:31])[CH3:27]
Reactant: C=CCOC(=O)C1=C(Sc2nc(C3=CCN(C(=O)OCC=C)[C@@H]3CO)cs2)[C@H](C)[C@@H]2[C@@H]([C@@H](C)O)C(=O)N12
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: CCCC[SnH](CCCC)CCCC
Agent: O=P([O-])([O-])[O-]
Solvent: CC(=O)O
Solvent: ClCCl
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)O)=C(Sc3nc(C4=CCN[C@@H]4CO)cs3)[C@H](C)[C@H]12
Reaction time: 0.05 h
Yield: 48.4 %

Procedure:
To a solution of allyl (4R,5S,6S)-3-({4-[(2S)-1-[(allyloxy)carbonyl]-2-(hydroxymethyl)-2,5-dihydro-1H-pyrrol-3-yl]-1,3-thiazol-2-yl}sulfanyl)-6-[(1R)-1-hydoxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (33 mg, 0.06 mmol) in dicloromethane (3 ml) were added at 0° C. acetic acid (8.6 μl, 0.15 mmol), tributyltin hydride (165 ml, 0.61 mmol) and bis(triphenylphosphine)palladium chloride (4.2 mg, 0.006 mmol), and the mixture was stirred at the same temperature for 3 minutes. To the reaction mixture were added phosphate buffer (50 mM, pH7, 25 ml) and dichloromethane (5 ml). After separation of the aqueous layer, the dichloromethane layer was extracted twice with water and the aqueous layer was washed twice with dichloromethane (3 ml). The organic solvent in the aqueous layer was evaporated under reduced pressure, and the residue was purified by polymer chromatography (CHP-20P). The fractions eluted with 1–3% aqueous THF solution were combined and lyophilized to give (4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-3-({4-[(2S)-2-(hydroxymethyl)-2,5-dihydro-1H-pyrrol-3-yl]-1,3-thiazol-2-yl}sulfanyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (12.3 mg, 48%) as a white amorphous.
Reaction SMILES: [CH2:1]([N:8]1[C@H:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C@H:11]([C:18]([O:20]CC)=[O:19])[N:10]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:9]1=[O:30])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>P([O-])([O-])([O-])=O>[CH2:1]([N:8]1[C@@H:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[C@@H:11]([C:18]([OH:20])=[O:19])[N:10]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:9]1=[O:30])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCOC(=O)[C@@H]1[C@H](C(=O)OCC)N(Cc2ccccc2)C(=O)N1Cc1ccccc1
Agent: O=P([O-])([O-])[O-]
Product: CCOC(=O)[C@H]1[C@@H](C(=O)O)N(Cc2ccccc2)C(=O)N1Cc1ccccc1
Yield: 85.9 %

Procedure:
A suspension of diethyl cis-1,3-dibenzyl-2-oxoimidazolidine-4,5-dicarboxylate (500 mg) in 0.1m phosphate buffer (pH 8.0, 50 ml) was treated with Pig Liver Esterase (manufactured by Sigma Lab., 1600 units, 10 mg) in a manner similar to that in Example 1 (1) to give (4S,5R)-1,3-dibenzyl-5-ethoxycarbonyl-2-oxoimidazolidine-4-carboxylic acid (400 mg). M.P., 108°-112° C. [α]D20 =+4.4° (c=1, CHCl3).
Reaction SMILES: N1C=CC=CC=1.[S:7]([O:14]S(C(F)(F)F)(=O)=O)([C:10]([F:13])([F:12])[F:11])(=[O:9])=[O:8].O[C@H:23]([CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([CH3:41])[CH:36]=1)[C:24]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:25]>C(Cl)Cl>[F:11][C:10]([F:13])([F:12])[S:7]([O:14][C@H:23]([CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([CH3:41])[CH:36]=1)[C:24]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:25])(=[O:9])=[O:8]
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Reactant: Cc1cccc(C[C@@H](O)C(=O)OCc2ccccc2)c1
Solvent: c1ccncc1
Solvent: ClCCl
Product: Cc1cccc(C[C@@H](OS(=O)(=O)C(F)(F)F)C(=O)OCc2ccccc2)c1

Procedure:
To a solution of pyridine (0.78 mL, 9.7 mmol) in CH2Cl2 (50 mL) at −10° C. is added triflic anhydride (1.68 mL, 10.0 mmol) over 15 min. A solution of benzyl (R)-2-hydroxy-3-(3-methylphenyl)-propionate (1.5 g, 5.55 mmol) in CH2Cl2 (15 mL) is then added dropwise over 30 min., and the mixture is warmed to room temp. over 1 h. The solution is diluted with CH2Cl2 (100 mL), washed with water (2×100 mL) and brine (100 mL), dried (MgSO4), and evaporated to yield benzyl (R)-2-trifluoromethanesulfonyloxy-3-(3-methylphenyl)-propionate as a yellowish oil.
Reaction SMILES: Br[C:2]1[C:10]2[C:5](=[N:6][C:7]([CH3:22])=[CH:8][C:9]=2[NH:11][S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=2)(=[O:14])=[O:13])[S:4][C:3]=1[CH3:23].[CH3:24][C:25]1[S:29][C:28](B(O)O)=[CH:27][CH:26]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>O1CCOCC1.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>[Cl:21][C:17]1[CH:16]=[C:15]([S:12]([NH:11][C:9]2[CH:8]=[C:7]([CH3:22])[N:6]=[C:5]3[S:4][C:3]([CH3:23])=[C:2]([C:28]4[S:29][C:25]([CH3:24])=[CH:26][CH:27]=4)[C:10]=23)(=[O:14])=[O:13])[CH:20]=[CH:19][CH:18]=1
Reactant: Cc1cc(NS(=O)(=O)c2cccc(Cl)c2)c2c(Br)c(C)sc2n1
Reactant: Cc1ccc(B(O)O)s1
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: O
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: Cc1cc(NS(=O)(=O)c2cccc(Cl)c2)c2c(-c3ccc(C)s3)c(C)sc2n1
Temperature: 120 °C
Yield: 15.4 %

Procedure:
Under nitrogen, N-(3-bromo-2,6-dimethylthieno[2,3-b]pyridin-4-yl)-3-chlorobenzenesulfonamide (Example 61) (100 mg, 0.232 mmol) was dissolved in 1,4-dioxane (1.5 mL) and water (0.7 mL). (5-Methyl-2-thienyl)boronic acid (49.3 mg, 0.347 mmol), tetrakis(triphenylphosphine)palladium(0) (26.8 mg, 0.023 mmol) and potassium carbonate (96 mg, 0.695 mmol) were added and the mixture heated in a microwave at 120° C. for 10 min (×2). Ethyl acetate (10 mL) was added and the mixture washed with water (2×5 mL). The organic layer was dried over MgSO4, filtered and the solvent removed in vacuo. The residue was purified by normal phase chromatography, eluting with a gradient of 0-30% ethyl acetate in cyclohexane and then further purified by MDAP (acidic conditions), to give the title compound (16 mg). LCMS (A) m/z: 449 [M+1]+, Rt 1.54 min (acidic).