Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:5]1[CH:39]=[CH:38][C:8]([C:9]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]3[N:19]=[C:20]([NH:26][C:27]4[CH:32]=[CH:31][C:30](F)=[C:29]([N+:34]([O-:36])=[O:35])[CH:28]=4)[C:21](=[O:25])[N:22]([CH3:24])[CH:23]=3)[C:13]=2[CH3:37])=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].CN.[CH3:42][N:43]1CCCC1=O.O>C1COCC1>[C:1]([C:5]1[CH:39]=[CH:38][C:8]([C:9]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]3[N:19]=[C:20]([NH:26][C:27]4[CH:32]=[CH:31][C:30]([NH:43][CH3:42])=[C:29]([N+:34]([O-:36])=[O:35])[CH:28]=4)[C:21](=[O:25])[N:22]([CH3:24])[CH:23]=3)[C:13]=2[CH3:37])=[O:10])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CN1CCCC1=O
Reactant: Cc1c(NC(=O)c2ccc(C(C)(C)C)cc2)cccc1-c1cn(C)c(=O)c(Nc2ccc(F)c([N+](=O)[O-])c2)n1
Agent: CN
Solvent: C1CCOC1
Solvent: O
Product: CNc1ccc(Nc2nc(-c3cccc(NC(=O)c4ccc(C(C)(C)C)cc4)c3C)cn(C)c2=O)cc1[N+](=O)[O-]
Temperature: 25 °C

Procedure:
A mixture of give 4-tert-butyl-N-{3-[6-(4-fluoro-3-nitro-phenylamino)-4-methyl-5-oxo-4,5-dihydro-pyrazin-2-yl]-2-methyl-phenyl}-benzamide (2) (600 mg; 1.13 mmol), methylamine (5 mL of a 2M solution in THF), and 1-methyl-2-pyrollidinone (10 mL) was heated at 60 degrees in a sealed pressure vessel for 16 hr. The mixture was cooled to room temperature, treated with water (30 mL) and filtered to give 4-tert-butyl-N-{2-methyl-3-[4-methyl-6-(4-methylamino-3-nitro-phenylamino)-5-oxo-4,5-dihydro-pyrazin-2-yl]-phenyl}-benzamide (3) as a red solid (501 mg).
Reaction SMILES: S(Cl)([Cl:3])=O.[Cl:5][C:6]1[C:7]([O:16][C:17]2[CH:28]=[CH:27][C:20]([O:21][CH:22]([CH3:26])[C:23](O)=[O:24])=[C:19]([F:29])[CH:18]=2)=[N:8][CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=1.C1C=CC=CC=1>CN(C)C=O>[Cl:5][C:6]1[C:7]([O:16][C:17]2[CH:28]=[CH:27][C:20]([O:21][CH:22]([CH3:26])[C:23]([Cl:3])=[O:24])=[C:19]([F:29])[CH:18]=2)=[N:8][CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=1
Reactant: CC(Oc1ccc(Oc2ncc(C(F)(F)F)cc2Cl)cc1F)C(=O)O
Reactant: O=S(Cl)Cl
Solvent: CN(C)C=O
Solvent: c1ccccc1
Product: CC(Oc1ccc(Oc2ncc(C(F)(F)F)cc2Cl)cc1F)C(=O)Cl
Reaction time: 3 h

Procedure:
Thionyl chloride (7.24 g, 0.0608 mole) was added to a stirred solution of 2-(4-(3-chloro-5-trifluoromethyl-2-pyridyloxy)-2-fluorophenoxy)propanoic acid (21.0 g, 0.0553 mole), benzene (150 ml), and dimethyl formamide (0.3 g). Refluxing was effected for three hours. The benzene and residual thionyl chloride were removed by distillation under vacuum. The resulting amber colored oil (21 g) was shown to be the desired acid chloride by NMR and IR spectroscopy. This material was used directly in subsequent reactions.
Reaction SMILES: [N:1]1([C:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[S:9][N:8]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[Cl:16][CH2:17][CH:18]=[CH:19][CH2:20]Cl.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>C1(C)C=CC=CC=1>[Cl:16][CH2:17][CH:18]=[CH:19][CH2:20][N:4]1[CH2:5][CH2:6][N:1]([C:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[S:9][N:8]=2)[CH2:2][CH2:3]1
Reactant: ClCC=CCCl
Reactant: c1ccc2c(N3CCNCC3)nsc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Product: ClCC=CCN1CCN(c2nsc3ccccc23)CC1
Reaction time: 2 h

Procedure:
A mixture of 3-(1-piperazinyl)-1,2-benzisothiazole (1 g; 4.56 mmol), 1,4-dichloro-2-butene (2.9 g; 22.8 mmol), anhydrous potassium carbonate (0.79 g; 5.7 mmol) and dry dimethylformamide (10 ml) was stirred at a bath temperature of 90° to 100° C. for 2 hours. After completion of the reaction, toluene (100 ml) was added to the mixture, which was washed three times with water (50 ml). The toluene layer was washed with a saturated sodium chloride solution and dried over magnesium sulfate. The crude oil thus obtained was purified by silica gel chromatography to give the objective compound. IR νmaxNujol (cm-1): 1590, 1560, 1490, 1450, 1420.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH:4]([CH2:7][CH2:8][OH:9])[CH2:3][CH2:2]1.C(N(CC)CC)C.[CH3:17][S:18](Cl)(=[O:20])=[O:19]>ClCCl>[CH3:17][S:18]([O:9][CH2:8][CH2:7][CH:4]1[CH2:5][CH2:6][O:1][CH2:2][CH2:3]1)(=[O:20])=[O:19]
Reactant: CS(=O)(=O)Cl
Reactant: OCCC1CCOCC1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OCCC1CCOCC1
Reaction time: 16 h
Yield: 77.2 %

Procedure:
To a stirring solution of 2-(4-oxanyl)ethanol (9.63 g, 74.0 mmol) in dry dichloromethane (350 mL) was added distilled triethylamine (20.62 mL, 96.2 mmol) at 0° C., followed by drop-wise addition of methanesulfonyl chloride (7.44 mL, 96.2 mmol) over 15 min. The reaction was stirred for 16 h under N2 and slowly allowed to come to ambient temperature. The reaction was washed with saturated NaHCO3 (100 mL) and the aqueous phase was extracted with dichloromethane (1×50 mL). The combined organic extracts were dried (K2CO3), filtered and concentrated by rotary evaporation to yield 11.9 g of a colorless oil (77.0% yield).
Reaction SMILES: [Br:1][C:2]1[CH:19]=[CH:18][C:5]2[N:6]3[CH:17]=[CH:16][C:15]4[C:7]3=[C:8]([CH:12]=[CH:13][CH:14]=4)[C:9](=O)[NH:10][C:4]=2[CH:3]=1.COC1C=CC(P2(=S)SP(=S)[S:29]2)=CC=1>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:19]=[CH:18][C:5]2[N:6]3[CH:17]=[CH:16][C:15]4[C:7]3=[C:8]([CH:12]=[CH:13][CH:14]=4)[C:9](=[S:29])[NH:10][C:4]=2[CH:3]=1
Reactant: O=C1Nc2cc(Br)ccc2-n2ccc3cccc1c32
Reactant: COc1ccc(P2(=S)S[PH](=S)S2)cc1
Solvent: Cc1ccccc1
Product: S=C1Nc2cc(Br)ccc2-n2ccc3cccc1c32
Reaction time: 8 h
Yield: 71.5 %

Procedure:
A mixture of 9-bromobenzo[b]pyrrolo[3,2,1-jk][1,4]benzodiazepin-6(7H)-one (12.8 g), 2,4-bis(4-methoxyphenyl-1,3-dithia-2,4-diphosphetane-2,4-disulfide (8.3 g), and toluene (500 ml) was refluxed for 2 hrs. The reaction mixture was allowed to stand overnight at room temperature. The precipitate was collected, washed with hexane, and dried overnight under vacuum at 40° C. to provide 9.6 g, (71.5%) of product. Recrystallization from chloroform gave the analytical sample, mp 214°-215° C.
Reaction SMILES: [CH2:1]([O:8][C@@H:9]1[C:13]([CH2:20][O:21][S:22]([CH3:25])(=[O:24])=[O:23])([CH2:14][O:15][S:16]([CH3:19])(=[O:18])=[O:17])[O:12][C@@H:11]([N:26]2[CH:34]=[C:32]([CH3:33])[C:30](=[O:31])[NH:29][C:27]2=[O:28])[C@@H:10]1[OH:35])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.[CH3:42][S:43](Cl)(=[O:45])=[O:44]>ClCCl>[CH2:1]([O:8][C@@H:9]1[C:13]([CH2:14][O:15][S:16]([CH3:19])(=[O:17])=[O:18])([CH2:20][O:21][S:22]([CH3:25])(=[O:24])=[O:23])[O:12][C@@H:11]([N:26]2[CH:34]=[C:32]([CH3:33])[C:30](=[O:31])[NH:29][C:27]2=[O:28])[C@@H:10]1[O:35][S:43]([CH3:42])(=[O:45])=[O:44])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CS(=O)(=O)Cl
Reactant: Cc1cn([C@@H]2OC(COS(C)(=O)=O)(COS(C)(=O)=O)[C@@H](OCc3ccccc3)[C@H]2O)c(=O)[nH]c1=O
Solvent: ClCCl
Solvent: c1ccncc1
Product: Cc1cn([C@@H]2OC(COS(C)(=O)=O)(COS(C)(=O)=O)[C@@H](OCc3ccccc3)[C@H]2OS(C)(=O)=O)c(=O)[nH]c1=O
Temperature: 0 °C

Procedure:
Nucleoside 27 (20 g, 37 mmol) was dissolved in anhyd dichloromethane (100 mL) and anhyd pyridine (100 mL) was added. The solution was cooled to 0° C. and methanesulfonyl chloride (4.4 mL, 56 mmol) was added dropwise. After 2 h the reaction was quenched with sat. aq NaHCO3 (200 mL), and the phases were separated. The aq phase was extracted with dichloromethane (2×150 mL), and the combined organic phases were washed with aq HCl (1 M, 2×200 mL), sat. aq NaHCO3 (2×250 mL) and brine (250 mL). The organic phase was dried (Na2SO4), filtered and the solvent was removed in vacuo. The crude product was co-evaporated with toluene affording 28 (22 g, 96%) as a white foam. Rf=0.41 (100% EtOAc); ESI-MS m/z found 635.0 ([MNa]+, calcd 635.1). All analytical data were identical to those previously reported.(H åkansson, A. E.; Koshkin, A.; Sørensen, M. D.; Wengel, J. J. Org. Chem. 2000, 65, 5161-5166)
Reaction SMILES: Cl.[CH2:2]([O:9][C:10]([N:12]1[CH2:16][CH2:15][CH2:14][CH:13]1[C:17]([O:19][CH2:20][CH3:21])=N)=[O:11])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.N1C=CC=CC=1.[SH2:28]>C1COCC1>[CH2:2]([O:9][C:10]([N:12]1[CH2:16][CH2:15][CH2:14][CH:13]1[C:17]([O:19][CH2:20][CH3:21])=[S:28])=[O:11])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: CCOC(=N)C1CCCN1C(=O)OCc1ccccc1
Reactant: S
Agent: Cl
Solvent: c1ccncc1
Solvent: C1CCOC1
Product: CCOC(=S)C1CCCN1C(=O)OCc1ccccc1
Temperature: -20 °C
Yield: 47 %

Procedure:
2-Ethoxycarbonimidoyl-pyrrolidine-1-carboxylic acid benzyl ester hydrochloride (42.8 g, 146.0 mmol) was dissolved in THF (150 mL) and cooled to −20° C. Pyridine (80 ml) was added to the reaction and H2S was bubbled through the reaction for 60 min. The reaction's temperature was maintained at −20° C. for 2 hours while stirring. The pH was adjust to pH=4 by addition of 5M HCl. The resulting solution was transferred to a separatory funnel and extracted with diethyl ether (3×100 mL). The organic layers were combined and washed with brine (100 ml). The organic layer was dried over MgSO4 and concentrated under vacuo to afford 20.0 g (47%) of 2-ethoxythiocarbonyl-pyrrolidine-1-carboxylic acid benzyl ester as a yellow oil.
Reaction SMILES: [Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([C:9]2[C:13]([CH3:14])=[C:12]([C:15]#[N:16])[N:11]([CH3:17])[N:10]=2)=[C:4]([F:18])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:25](Br)[C:26]#[CH:27]>CC(C)=O>[Cl:1][C:2]1[C:7]([O:8][CH2:27][C:26]#[CH:25])=[CH:6][C:5]([C:9]2[C:13]([CH3:14])=[C:12]([C:15]#[N:16])[N:11]([CH3:17])[N:10]=2)=[C:4]([F:18])[CH:3]=1
Reactant: Cc1c(-c2cc(O)c(Cl)cc2F)nn(C)c1C#N
Reactant: C#CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: C#CCOc1cc(-c2nn(C)c(C#N)c2C)c(F)cc1Cl
Temperature: 22 °C
Reaction time: 0.17 h

Procedure:
1.33 g of 3-(4-chloro-2-fluoro-5-hydroxyphenyl)-4-methyl-5-cyano-1-methyl-[1H]-pyrazole (Example H6) are dissolved in 25 ml of acetone, and 1.38 g of potassium carbonate are added. The reaction mixture is stirred for 10 minutes at 22° C., and 0.89 g (0.56 ml) of propargyl bromide is then added dropwise with stirring, and stirring is continued for 5 hours at this temperature. The solvent is subsequently distilled off in vacuo and the residue is taken up in diethyl ether. After the etheric solution has been washed with water and saline and the solvent evaporated off, the desired product is obtained in a yield of 1.36 g (89.9% of theory).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[C:10]([CH:13]=[CH:14][CH:15]=2)[CH:11]=O)[CH:5]=[CH:4][N:3]=1.[N:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH2:22][CH2:23][NH2:24])[CH:17]=1>>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[C:10]([CH:13]=[CH:14][CH:15]=2)[CH2:11][NH:24][CH2:23][CH2:22][C:18]2[CH:17]=[N:16][CH:21]=[CH:20][CH:19]=2)[CH:5]=[CH:4][N:3]=1
Reactant: NCCc1cccnc1
Reactant: O=Cc1cccc(-c2ccnc(Cl)n2)c1
Product: Clc1nccc(-c2cccc(CNCCc3cccnc3)c2)n1

Procedure:
Intermediate 1 was coupled with 2-pyridin-3-yl-ethylamine following procedure B. LC-MS showed the product had the expected M+H+ of 325.
Reaction SMILES: [CH3:1][C:2]([OH:8])([C:4]([CH3:7])([OH:6])[CH3:5])[CH3:3].CC(C(C)C)=C.OO.[CH:17](O)=[O:18]>>[CH:17]([O:6][C:4]([C:2]([OH:8])([CH3:3])[CH3:1])([CH3:7])[CH3:5])=[O:18]
Reactant: CC(C)(O)C(C)(C)O
Reactant: O=CO
Agent: C=C(C)C(C)C
Agent: OO
Product: CC(C)(O)C(C)(C)OC=O

Procedure:
A process for preparing 2,3-dimethyl-2,3-butandiol which comprises introducing into a reaction vessel containing formic acid at 50° to 70° C. while stirred, 2,3-dimethylbutene and hydrogen peroxide, said 2,3-dimethylbutene and hydrogen peroxide being introduced into said formic acid simultaneously but separately and thereafter hydrolyzing pinacol monoformate so formed.
Reaction SMILES: [CH:1]1[C:13]2CC3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.[CH3:14][C:15]([CH3:18])([O-])[CH3:16].[K+].IC>CS(C)=O>[CH3:14][C:15]1([CH3:18])[C:13]2[CH:1]=[CH:2][CH:3]=[CH:4][C:5]=2[C:6]2[C:16]1=[CH:10][CH:9]=[CH:8][CH:7]=2
Reactant: CC(C)(C)[O-]
Reactant: c1ccc2c(c1)Cc1ccccc1-2
Agent: [K+]
Solvent: CS(C)=O
Solvent: CI
Product: CC1(C)c2ccccc2-c2ccccc21
Temperature: 10 °C
Reaction time: 24 h
Yield: 81.5 %

Procedure:
A 2000 mL round flask was charged with 9H-fluorene (50 g, 300.1 mmol) and potassium t-butoxide (77.0 g, 721.9 mmol), and then 700 mL of DMSO was slowly injected thereto. Under nitrogen atmosphere, iodomethane (113.5 g, 800 mmol) was slowly dropped through a dropping funnel while the reactor temperature was maintained at 10° C. or lower. The mixture was stirred at room temperature for 24 hours, and the reaction was terminated by addition of 500 mL of distilled water. The organic layer collected by extraction with n-hexane was dried over magnesium sulfate, followed by removal of volatile materials, and then purified with n-hexane by using silica gel column chromatography tube, followed by drying, to thereby obtain 47.5 g of 9,9-dimethyl-9H-fluorene (yield: 81.50%) as white solid.
Reaction SMILES: [N+:1]([O:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]([OH:11])=O)([O-:3])=[O:2].C(Cl)(=O)C([Cl:15])=O>C(Cl)Cl.CN(C=O)C>[N+:1]([O-:3])([O:4][CH2:5][CH2:6][CH2:7][CH2:8][C:9]([Cl:15])=[O:11])=[O:2]
Reactant: O=C(O)CCCCO[N+](=O)[O-]
Reactant: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Product: O=C(Cl)CCCCO[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 12 h
Yield: 82.6 %

Procedure:
5-(Nitrooxy)pentanoic acid (489 mg, 3.00 mmol; US Patent 2006/189603) was dissolved in anhydrous DCM (30 mL) under N2, cooled to 0° C., and added in succession anhydrous DMF (1 drop) and oxalyl chloride (262 uL, 3.00 mmol). Allowed to stir at ambient temperature for 12 h. 13CNMR displayed acid chloride (δ171 ppm) with small amount of carboxylic acid (˜δ173 ppm). Evaporated and dried in vacuo to yield 450 mg (80%) of 5-chloro-5-oxopentyl nitrate as light yellow oil, which was used without further purification.
Reaction SMILES: [CH2:1]([N:4]([CH2:17][CH2:18][CH3:19])[S:5]([C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=1)(=[O:7])=[O:6])[CH2:2][CH3:3].C(N1C=CN=C1)(N1C=CN=C1)=O.C(=O)=O.[NH2:35][C@@H:36]1[CH2:45][CH2:44][C:43]2[C:38](=[C:39]([N:46]3[CH2:51][CH2:50][N:49]([CH3:52])[CH2:48][CH2:47]3)[CH:40]=[CH:41][CH:42]=2)[CH2:37]1>CN(C)C=O>[CH3:52][N:49]1[CH2:50][CH2:51][N:46]([C:39]2[CH:40]=[CH:41][CH:42]=[C:43]3[C:38]=2[CH2:37][C@H:36]([NH:35][C:12](=[O:14])[C:11]2[CH:10]=[CH:9][C:8]([S:5]([N:4]([CH2:1][CH2:2][CH3:3])[CH2:17][CH2:18][CH3:19])(=[O:6])=[O:7])=[CH:16][CH:15]=2)[CH2:45][CH2:44]3)[CH2:47][CH2:48]1
Reactant: CN1CCN(c2cccc3c2C[C@H](N)CC3)CC1
Reactant: CCCN(CCC)S(=O)(=O)c1ccc(C(=O)O)cc1
Agent: O=C(n1ccnc1)n1ccnc1
Agent: O=C=O
Solvent: CN(C)C=O
Product: CCCN(CCC)S(=O)(=O)c1ccc(C(=O)N[C@@H]2CCc3cccc(N4CCN(C)CC4)c3C2)cc1
Temperature: 75 °C
Reaction time: 24 h
Yield: 27.6 %

Procedure:
To a solution of 4-(N,N-dipropylaminosulphonyl)benzoic acid (120 mg, 0.43 mmol) in anhydrous N,N-dimethylformamide (25 mL) was added 1,1′-carbonyldiimidazole (73 mg, 0.45 mmol) and the reaction was heated at 75° C. When the carbon dioxide evolution had ceased (after 30 min), the reaction was cooled to room temperature and a solution of (R)-2-amino-8-(4-methylpiperazin-1-yl)-1,2,3,4-tetrahydronaphthalene (100 mg, 0.41 mmol) in anhydrous N,N-dimethylformamide (5 mL) was added. The reaction was allowed to stir at ambient temperature for 24 h and the solvent was evaporated in vacuo. Purification on a silica gel column using chloroform/ethanol saturated with NH3 (100:3) as the eluent gave 58 mg (27% yield) of the title compound as a viscous oil: [α]21D −370 (c 0.50, chloroform); EIMS (70 eV) m/z (relative intensity) 512 (11, M+).
Reaction SMILES: Cl[C:2]1[C:7]2[C:8](=[O:22])[N:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=3[O:20][CH3:21])[CH2:10][C:6]=2[C:5]([F:23])=[C:4]([NH:24][C@@H:25]2[CH2:30][CH2:29][CH2:28][CH2:27][C@@H:26]2[NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[N:3]=1.CC1(C)C(C)(C)OB([C:47]2[CH:48]=[N:49][N:50]3[CH:55]=[CH:54][CH:53]=[CH:52][C:51]=23)O1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.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>[CH3:21][O:20][C:13]1[CH:14]=[C:15]([O:18][CH3:19])[CH:16]=[CH:17][C:12]=1[CH2:11][N:9]1[CH2:10][C:6]2[C:5]([F:23])=[C:4]([NH:24][C@@H:25]3[CH2:30][CH2:29][CH2:28][CH2:27][C@@H:26]3[NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[N:3]=[C:2]([C:47]3[CH:48]=[N:49][N:50]4[CH:55]=[CH:54][CH:53]=[CH:52][C:51]=34)[C:7]=2[C:8]1=[O:22]
Reactant: COc1ccc(CN2Cc3c(F)c(N[C@@H]4CCCC[C@@H]4NC(=O)OC(C)(C)C)nc(Cl)c3C2=O)c(OC)c1
Reactant: CC1(C)OB(c2cnn3ccccc23)OC1(C)C
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: [Na+]
Solvent: COCCOC
Solvent: O
Product: COc1ccc(CN2Cc3c(F)c(N[C@@H]4CCCC[C@@H]4NC(=O)OC(C)(C)C)nc(-c4cnn5ccccc45)c3C2=O)c(OC)c1
Temperature: 85 °C
Reaction time: 3 h
Yield: 46.2 %

Procedure:
A mixture of tert-butyl (1S,2R)-2-(4-chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate (100 mg, 0.182 mmol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolo[1,5-a]pyridine (53.4 mg, 0.219 mmol), sodium carbonate (48.3 mg, 0.455 mmol) and tetrakis(triphenylphosphine)palladium (21.05 mg, 0.018 mmol) in DME (1 mL) and H2O (0.333 mL) was stirred at 85° C. for 3 h. Following reaction, the mixture was filtered and the filtrate was diluted with EtOAc and H2O. The aqueous phase was extracted with EtOAc. The organic phases were combined, washed with brine, dried over MgSO4, and evaporated. The residue was purified by chromatography on SiO2 to give the title compound (53 mg, 46.1%). 1H NMR (500 MHz, CDCl3) δ ppm 1.17-2.03 (m, 17 H), 3.74-3.81 (m, 3 H), 3.84-3.89 (m, 3 H), 4.04 (br s, 1 H), 4.26 (br s, 2 H), 4.46 (br s, 1 H), 4.71 (br s, 2 H), 6.36-6.55 (m, 2 H), 6.83 (d, J=5.86 Hz, 1 H), 7.18-7.31 (m, 2 H), 8.42 (br s, 1 H), 8.47-8.57 (m, 1 H), 9.42 (br s, 1 H).
Reaction SMILES: [C@@H:1]1([C:7]([OH:9])=[O:8])[O:3][C@@H:2]1[C:4]([OH:6])=[O:5].[OH-:10].[Na+:11]>>[C:7]([C@@H:1]([C@H:2]([C:4]([O-:6])=[O:5])[OH:10])[OH:3])([O-:9])=[O:8].[Na+:11].[Na+:11]
Reactant: [OH-]
Reactant: O=C(O)[C@H]1O[C@H]1C(=O)O
Agent: [Na+]
Product: O=C([O-])[C@H](O)[C@@H](O)C(=O)[O-]
Temperature: 35 °C
Reaction time: 4 h
Yield: 95 %

Procedure:
Clean microbic cells obtained similarly to Example 3 were placed in 100 ml of an aqueous solution containing as the substrate 1.0 g of cis-epoxysuccinic acid and having the pH value thereof adjusted to 8.0 with an aqueous sodium hydroxide solution and agitated at 35° C for four hours. The substrate was wholly used up to produce 1.40 g of sodium L(+)-tartrate. The yield was 95 percent. The reaction mixture was treated by following the procedure of Example 2. The L(+)-tartaric acid consequently obtained was found to have an optical purity of 100 percent.
Reaction SMILES: [C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[O-]CC.[Na+].Br[CH2:17][CH2:18][O:19][CH2:20][CH2:21]Br>C(O)C>[O:19]1[CH2:20][CH2:21][C:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])([C:1]([O:9][CH2:10][CH3:11])=[O:8])[CH2:17][CH2:18]1
Reactant: CCOC(=O)CC(=O)OCC
Reactant: BrCCOCCBr
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Product: CCOC(=O)C1(C(=O)OCC)CCOCC1
Reaction time: 0.5 h
Yield: 61.3 %

Procedure:
Diethyl malonate (32.0 g) was added to a solution of sodium ethoxide (1 equivalent) in ethanol and the solution was stirred for 30 min. 2-Bromoethylether (46.0 g) was then added and the mixture was stirred at reflux for 3 h. The mixture was then cooled, evaporated in vacuo and the residue partitioned between water and dichloromethane. The organic layer was separated and washed with water and brine, then dried (MgSO4) and evaporated. The residue was then purified by flash column chromatography on silica gel, eluting with 4:1 hexanes/ether, to give the title compound (28.0 g) as colourless liquid.
Reaction SMILES: [N:1]([CH2:4][C@@H:5]1[O:9][C:8](=[O:10])[N:7]([C:11]2[CH:16]=[CH:15][C:14]([I:17])=[C:13]([F:18])[CH:12]=2)[CH2:6]1)=[N+:2]=[N-:3].[CH3:19][Si:20]([C:23]#[CH:24])([CH3:22])[CH3:21]>CN(C=O)C>[F:18][C:13]1[CH:12]=[C:11]([N:7]2[CH2:6][C@H:5]([CH2:4][N:1]3[CH:24]=[C:23]([Si:20]([CH3:22])([CH3:21])[CH3:19])[N:3]=[N:2]3)[O:9][C:8]2=[O:10])[CH:16]=[CH:15][C:14]=1[I:17]
Reactant: C#C[Si](C)(C)C
Reactant: [N-]=[N+]=NC[C@H]1CN(c2ccc(I)c(F)c2)C(=O)O1
Solvent: CN(C)C=O
Product: C[Si](C)(C)c1cn(C[C@H]2CN(c3ccc(I)c(F)c3)C(=O)O2)nn1
Temperature: 95 °C
Yield: 99.9 %

Procedure:
A solution of (5R)-5-azidomethyl-3-(3-fluoro-4-iodophenyl)-oxazolidin-2-one (1023, 11.60 g, 32.0 mmol) in anhydrous DMF (50 mL) was treated with trimethylsilylacetylene (4.70 g, 6.77 mL, 48.0 mmol, 1.5 equiv) at room temperature, and the resulting reaction mixture was warmed up to 90-100° C. for 20 h. When TLC and HPLC/MS showed that the cycloaddition reaction was complete, the reaction mixture was cooled down to room temperature before being concentrated in vacuo. The residue was further dried in vacuo to afford the crude, (5R)-3-(3-fluoro-4-iodo-phenyl)-5-(4-trimethylsilanyl-[1,2,3]triazol-1-ylmethyl)-oxazolidin-2-one (1024, 14.72 g, 14.72 g theoretical, 100%) as brown oil, which was directly used in the subsequent reaction without further purification. For 1024: 1H NMR (300 MHz, DMSO-d6) δ 0.01 (s, 9H, SiCH3), 3.67 (dd, 1H, J=6.4, 9.2 Hz), 4.01 (t, 1H, J=5.4 Hz), 4.59 (d, 2H, J=4.9 Hz), 4.91-4.94 (m, 1H), 6.88 (dd, 1H, J=2.4, 8.7 Hz), 7.22 (dd, 1H, J=2.4, 8.7 Hz), 7.58 (dd, 1H, J=7.5, 8.7 Hz), 7.73 (s, 1H, triazole-H); C15H18FIN4O2Si, LCMS (EI) m/e 461 (M++H).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[CH:46]1([NH:51][C:52]2[CH:57]=[CH:56][C:55]([S:58]([O:61][C:62]3[CH:71]=[CH:70][C:65]4[NH:66][C:67]([NH2:69])=[N:68][C:64]=4[CH:63]=3)(=[O:60])=[O:59])=[CH:54][CH:53]=2)[CH2:50][CH2:49][CH2:48][CH2:47]1>CN(C)C=O>[CH:46]1([NH:51][C:52]2[CH:57]=[CH:56][C:55]([S:58]([O:61][C:62]3[CH:71]=[CH:70][C:65]4[NH:66][C:67]([NH:69][C:10](=[O:12])[CH2:9][NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[N:68][C:64]=4[CH:63]=3)(=[O:59])=[O:60])=[CH:54][CH:53]=2)[CH2:50][CH2:49][CH2:48][CH2:47]1
Reactant: CC(C)(C)OC(=O)NCC(=O)O
Reactant: Nc1nc2cc(OS(=O)(=O)c3ccc(NC4CCCC4)cc3)ccc2[nH]1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)NCC(=O)Nc1nc2cc(OS(=O)(=O)c3ccc(NC4CCCC4)cc3)ccc2[nH]1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
11.3 mg of N-(tert-butoxycarbonyl)glycine, 25 mg HBTU and 12 μl diisopropylethylamine were taken up in 0.4 ml dimethylformamide. Reaction mixture was stirred at room temperature for one hour and 5-(4-cyclopentylaminophenylsulfonyloxy)-1H-benzimidazole-2-ylamine was added in 0.2 ml dimethylformamide. Reaction mixture was then stirred at room temperature for 24 hours. Solvent was evaporated in a Jouan model RC 10.10 centrifuge evaporator and title compound was solubilised in 0.5 ml dimethylsulfoxide for LCMS trigged purification yielding 2.4 mg of N-[5-(4-cyclopentylaminophenylsulfonyloxy)-1H-benzimidazole-2-yl]-tert-butoxycarbonylglycineamid. (LC/MS analysis: retention time=3.87 min., mass spectrum: 530.38, [M+H]+).