Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [SH:1][C:2]1[S:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.[NH3:11].O=O>CC([O-])=O.CC([O-])=O.[Cu+2].O.O>[CH:8]1[CH:7]=[C:5]2[N:6]=[C:2]([S:1][S:1][C:2]3[S:3][C:4]4[C:5](=[CH:7][CH:8]=[CH:9][CH:10]=4)[N:11]=3)[S:3][C:4]2=[CH:10][CH:9]=1
Reactant: N
Reactant: Sc1nc2ccccc2s1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Agent: O=O
Solvent: O
Product: c1ccc2sc(SSc3nc4ccccc4s3)nc2c1
Temperature: 50 °C

Procedure:
Following the procedure of Example 24, 50 g (0.3 mole) of 2-mercaptobenzothiazole, 8 mg (0.04 mMole) of Cu(OAc)2.H2O, 40.8 g (2.4 moles) of ammonia and 300 g of water were heated to 50° C., intensively stirred and placed under an oxygen pressure of 4 bars. Uptake of oxygen was immediately recorded and a deposit of dibenzothiazolyl disulphide was formed. After a reaction time of 2.5 hours, the 2-mercaptobenzothiazole conversion amounted to 95.4% and the yield of dibenzothiazolyl disulphide to 94.1% of the theoretical yield (selectivity: 98.6%).
Reaction SMILES: C(O[C:4](=[O:14])[CH2:5][C:6](=O)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)C.Cl.[C:16]([NH2:24])(=[NH:23])[C:17]1[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=1>>[C:7]1([C:6]2[N:24]=[C:16]([C:17]3[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=3)[N:23]=[C:4]([OH:14])[CH:5]=2)[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1
Reactant: N=C(N)c1ccncc1
Reactant: CCOC(=O)CC(=O)c1ccccc1
Agent: Cl
Product: Oc1cc(-c2ccccc2)nc(-c2ccncc2)n1

Procedure:
The title compound was prepared from 3-oxo-3-phenyl-propionic acid ethyl ester and isonicotinamidine hydrochloride according to general procedure 1. 1H NMR (DMSO-d6, 400 MHz) δ 7.08 (s, 1H), 7.50-7.55 (m, 3H), 8.17-8.25 (m, 4 H), 8.88 (d, J=4.4 Hz, 2H), 10-12 (br s, 1H); MS: m/z(ESI) 250 (M+H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:16]([CH:17]([CH3:21])[C:18]([OH:20])=O)[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[N:9]=2)=[CH:4][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH2:34]([NH:37][CH2:38][CH2:39][CH3:40])[CH2:35][CH3:36]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:16]([C@@H:17]([CH3:21])[C:18]([N:37]([CH2:38][CH2:39][CH3:40])[CH2:34][CH2:35][CH3:36])=[O:20])[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[N:9]=2)=[CH:6][CH:7]=1
Reactant: CC(C(=O)O)n1c(-c2ccc(Cl)cc2)nc2cccnc21
Reactant: CCCNCCC
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: CCCN(CCC)C(=O)[C@H](C)n1c(-c2ccc(Cl)cc2)nc2cccnc21
Temperature: 50 °C
Yield: 52.1 %

Procedure:
A solution of (S)-2-(4-chlorophenyl-α-methyl-3H-imidazo[4,5-b]pyridine-3-acetic acid (5.0 g, 0.0166 mole), 1,1'-carbonyldiimidazole (3.21 g, 0.0198 mole) and dry tetrahydrofuran (100 ml) was stirred at room temperature for 3 hours with nitrogen bubbling through it. A solution of dipropylamine (5.04 g, 0.050 mole) in tetrahydrofuran (7 ml) was added and the solution was heated at 50° C. overnight under nitrogen. The solvents were evaporated under reduced pressure and the resulting oil was partitioned between ethyl acetate (50 ml) and water (50 ml). The layers were separated and the aqueous layer was re-extracted with ethyl acetate (50 ml). The combined organic layers were washed once with water (50 ml) followed by two (50 ml) portions of 5% potassium hydroxide solution and then by water again (50 ml). The organic layer was dried over magnesium sulfate, charcoaled, filtered and evaporated to an oil which was crystallized from hot isopropyl ether. The solid was collected by filtration, and dried under high vacuum at room temperature to give 3.33 g (52%) of title compound, mp 96°-99° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([CH:11]1[CH2:17][CH:16]2[N:18]([CH3:19])[CH:13]([CH2:14][CH2:15]2)[CH2:12]1)=O.[ClH:20].[NH2:21][OH:22].C([O-])(=O)C.[NH4+]>C(O)C.O>[ClH:20].[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1/[C:9](/[CH:11]1[CH2:17][CH:16]2[N:18]([CH3:19])[CH:13]([CH2:14][CH2:15]2)[CH2:12]1)=[N:21]\[OH:22]
Reactant: NO
Reactant: CN1C2CCC1CC(C(=O)c1ccc(F)cc1F)C2
Agent: CC(=O)[O-]
Agent: Cl
Agent: [NH4+]
Solvent: CCO
Solvent: O
Product: CN1C2CCC1CC(/C(=N/O)c1ccc(F)cc1F)C2

Procedure:
A mixture of (2,4-difluorophenyl)(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)methanone (20 g), hydroxylamine hydrochloride (10.6 g) and ammonium acetate (18.7 g) was heated in 67.5 ml of refluxing ethanol-water (3.2 mixture) for 19 hours. The mixture was concentrated to approximately half of its original volume, and the precipitated solid (21.3 g) was collected.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7](OS(C(F)(F)F)(=O)=O)[CH:6]=[CH:5]2.[Br-].[Li+].[CH:22]([Mg]Br)([CH3:24])[CH3:23]>O1CCCC1>[Br:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH:22]([CH3:24])[CH3:23])[CH:8]=2)[CH:3]=1
Reactant: CC(C)[Mg]Br
Reactant: O=S(=O)(Oc1ccc2cc(Br)ccc2c1)C(F)(F)F
Agent: [Br-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CC(C)c1ccc2cc(Br)ccc2c1
Temperature: 80 °C
Yield: 33 %

Procedure:
Under an atmospheric argon gas flow, trifluoromethane sulfonic acid-6-bromo-2-naphthyl ester in an amount of 32 g (90 mmol), dichloro(diphenylphosphinoferrocene)palladium in an amount of 3.6 g (5% by mol), lithium bromide in an amount of 7.8 g (90 mmol) and desiccated tetrahydrofuran in an amount of 100 milliliter were placed into three necked-flask equipped with cooling pipe and having a capacity of 500 milliliter, and then, the resultant solution was cooled down to −20° C. After slowly dripping isopropylmagnesiumbromide in an amount of 90 milliliter (90 mmol, 1 mol/liter (tetrahydrofuran)) into the flask, the resultant solution was stirred under heating at the temperature of 80° C. for 4 hours. After the reaction terminated, adding dilute hydrochloric acid in an amount of 100 milliliter into the reacted solution, an organic layer was separated and washed with the use of sodium bicarbonate solution and sodium chloride solution, followed by drying with the use of magnesium sulfate. After removing the solvent by distillation by means of a rotary evaporator, the resultant crude product was refined by means of column chromatography (silicagel, hexane/dichloromethane=90/10), and as a result, 9.4 g of aimed compound (white crystal) was obtained (yield: 33%).
Reaction SMILES: [Si:1]([O:8][C@@H:9]1[C@@H:13]([CH2:14]I)[O:12][C@@H:11]([N:16]2[CH:24]=[C:22]([CH3:23])[C:20](=[O:21])[NH:19][C:17]2=[O:18])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[N-:25]=[N+:26]=[N-:27].[Na+]>CN(C=O)C.C(OCC)(=O)C>[Si:1]([O:8][C@@H:9]1[C@@H:13]([CH2:14][N:25]=[N+:26]=[N-:27])[O:12][C@@H:11]([N:16]2[CH:24]=[C:22]([CH3:23])[C:20](=[O:21])[NH:19][C:17]2=[O:18])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: [N-]=[N+]=[N-]
Reactant: Cc1cn([C@H]2C[C@H](O[Si](C)(C)C(C)(C)C)[C@@H](CI)O2)c(=O)[nH]c1=O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Cc1cn([C@H]2C[C@H](O[Si](C)(C)C(C)(C)C)[C@@H](CN=[N+]=[N-])O2)c(=O)[nH]c1=O
Temperature: 0 °C
Yield: 90 %

Procedure:
To a stirred solution of the 3'-O-t-butyldimethylsilyl-5'-iodo-5'-deoxythymidine (10.8 g, 20 mmol) prepared according to the method of Example 25 in dry DMF (50 ml) was added sodium azide (3.9 g, 60 mmol) and the mixture heated at 0° C. for 12 hours. Then the reaction mixture was diluted with ethyl acetate (200 ml) washed with water (2×50 ml) and brine (50 ml) and then dried with sodium sulfate. The title compound was purified by flash chromatography using 50% ethyl acetate in hexance in 90% yield.
Reaction SMILES: C(OC(=O)[NH:7][C:8]([CH3:42])([C:23]1[NH:24][C:25]([C:28]2[CH:33]=[CH:32][C:31]([CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])=[CH:30][CH:29]=2)=[CH:26][N:27]=1)[CH2:9][O:10][P:11]([O:18]C(C)(C)C)([O:13]C(C)(C)C)=[O:12])(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl.CCOCC>[NH2:7][C:8]([C:23]1[NH:24][C:25]([C:28]2[CH:29]=[CH:30][C:31]([CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])=[CH:32][CH:33]=2)=[CH:26][N:27]=1)([CH3:42])[CH2:9][O:10][P:11](=[O:12])([OH:18])[OH:13]
Reactant: CCCCCCCCc1ccc(-c2cnc(C(C)(COP(=O)(OC(C)(C)C)OC(C)(C)C)NC(=O)OC(C)(C)C)[nH]2)cc1
Solvent: ClCCl
Solvent: CCOCC
Solvent: O=C(O)C(F)(F)F
Product: CCCCCCCCc1ccc(-c2cnc(C(C)(N)COP(=O)(O)O)[nH]2)cc1
Reaction time: 4 h

Procedure:
To a stirring solution of 8 (22 mg, 0.035 mmol) in CH2Cl2 (1 mL) was added trifluoroacetic acid (1 mL) and stirring was continued 4 hours. Solvent and excess trifluoroacetic acid were removed in vacuo to afford a brown oil. The oil was diluted with ether and concentrated in vacuo 5 times on a rotary evaporator to afford a white solid which was placed in a fritted funnel and washed with cold ether producing VPC24287 (13 mg, 91%) as a powdery white solid. Rf=0 (4:1 CHCl3/methanol).
Reaction SMILES: [O:1]=[C:2]1[C@@H:5]([NH:6][C:7](=[O:16])[O:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:4][NH:3]1.[CH2:17]([N:19]([CH2:22][CH3:23])[CH2:20][CH3:21])[CH3:18].[C:24]1([CH3:36])[CH:29]=[CH:28][C:27]([S:30]([N:33]=[C:34]=[O:35])(=[O:32])=[O:31])=[CH:26][CH:25]=1>O1CCCC1>[CH2:17]([NH+:19]([CH2:22][CH3:23])[CH2:20][CH3:21])[CH3:18].[CH3:36][C:24]1[CH:29]=[CH:28][C:27]([S:30]([NH:33][C:34]([N:3]2[CH2:4][C@H:5]([NH:6][C:7](=[O:16])[O:8][CH2:9][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:2]2=[O:1])=[O:35])(=[O:32])=[O:31])=[CH:26][CH:25]=1
Reactant: Cc1ccc(S(=O)(=O)N=C=O)cc1
Reactant: CCN(CC)CC
Reactant: O=C(N[C@H]1CNC1=O)OCc1ccccc1
Solvent: C1CCOC1
Product: CC[NH+](CC)CC
Product: Cc1ccc(S(=O)(=O)NC(=O)N2C[C@H](NC(=O)OCc3ccccc3)C2=O)cc1
Reaction time: 2 h

Procedure:
(S)-(2-Oxo-3-azetidinyl)carbamic acid, phenylmethyl ester (220 mgs) was dissolved in dry tetrahydrofuran (10 ml) and stirred well under nitrogen. Triethylamine (139 μl) was added, followed by p-toluenesulfonyl isocyanate (153 μl, 1 mmol). After 2 to 3 hours of stirring a crystalline material starts to precipitate out. After 2 hours of further stirring, the solid was removed by filtration, washed with a small volume of acetonitrile and dried in vacuo. Yield of the triethylamine salt is 332 mg, melting point 128°-130° C.
Reaction SMILES: [Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1.[Cl:19][C:20]1[CH:21]=[C:22]([NH:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=2[NH:42][C:43](=[O:49])[CH2:44][CH2:45][C:46](O)=[O:47])[CH:23]=[CH:24][C:25]=1[C:26](=[O:34])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[CH3:33].[O:50]([CH2:57][CH2:58][CH2:59][CH2:60][NH2:61])[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1.Cl>CO>[Cl:19][C:20]1[CH:21]=[C:22]([NH:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=2[NH:42][C:43](=[O:49])[CH2:44][CH2:45][C:46]([NH:61][CH2:60][CH2:59][CH2:58][CH2:57][O:50][C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)=[O:47])[CH:23]=[CH:24][C:25]=1[C:26](=[O:34])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[CH3:33]
Reactant: Cc1ccccc1C(=O)c1ccc(Nc2ccccc2NC(=O)CCC(=O)O)cc1Cl
Reactant: NCCCCOc1ccccc1
Agent: COc1nc(OC)nc([N+]2(C)CCOCC2)n1
Agent: Cl
Agent: [Cl-]
Solvent: CO
Product: Cc1ccccc1C(=O)c1ccc(Nc2ccccc2NC(=O)CCC(=O)NCCCCOc2ccccc2)cc1Cl
Temperature: 25 °C
Reaction time: 18 h

Procedure:
4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-ium chloride (DMT-MM) (69 mg, 0.25 mmol) was added to a solution of N-(2-{[3-chloro-4-(2-methylbenzoyl)phenyl]amino}phenyl)-succinamic acid (100 mg, 0.23 mmol) (disclosed in WO 01/05746) and 4-phenoxybutylamine (30 mg, 0.25 mmol) in methanol (2.0 mL). The reaction mixture was stirred at room temperature for 18 h. The reaction mixture was poured into 1 N HCl (aq.) and was extracted with EtOAc (×2). The combined organic phases were washed with water, dried (MgSO4), filtered and concentrated in vacuo. The crude product was purified by flash chromatography using DCM/MeOH/NH3(aq.) 95:5:0.5 as the eluent to afford the title compound as a yellow solid.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[CH3:6][O:7][C:8]1[CH:15]=[CH:14][C:11]([CH2:12]Cl)=[CH:10][CH:9]=1>C(#N)C>[CH3:6][O:7][C:8]1[CH:15]=[CH:14][C:11]([CH2:12][N:1]2[CH:5]=[CH:4][N:3]=[CH:2]2)=[CH:10][CH:9]=1
Reactant: COc1ccc(CCl)cc1
Reactant: c1c[nH]cn1
Solvent: CC#N
Product: COc1ccc(Cn2ccnc2)cc1
Yield: 69.3 %

Procedure:
To a stirred solution of imidazole (25.53 g, 375 mmole) in acetonitrile (625 ml) was added p-methoxybenzyl chloride (16.95 ml, 125 mmole). The reaction was refluxed for 16 hours, evaporated to dryness, and redissolved in methylene chloride and saturated sodium bicarbonate. The organic layer was extracted with water twice. Standard acid/base workup gave N-p-methoxybenzylimidazole (16.3 g, 69%) which was used without further purification:
Reaction SMILES: [CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH:2]1[NH:11][NH:12][C:13]([O-:15])=[O:14])[CH2:8]2.C(=O)([O-])O.[Na+].[Cl:21][CH2:22][C:23](Cl)=[O:24].O>ClCCl>[Cl:21][CH2:22][C:23]([N:11]([CH:2]1[CH:3]2[CH2:4][CH:5]3[CH2:6][CH:7]([CH2:8][CH:1]1[CH2:10]3)[CH2:9]2)[NH:12][C:13]([O:15][CH2:10][C:1]1[CH:8]=[CH:7][CH:9]=[CH:3][CH:2]=1)=[O:14])=[O:24]
Reactant: O=C([O-])NNC1C2CC3CC(C2)CC1C3
Reactant: O=C(Cl)CCl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: O=C(NN(C(=O)CCl)C1C2CC3CC(C2)CC1C3)OCc1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 144.8 %

Procedure:
Under an argon atmosphere, a solution of 2-(adamantan-2-yl)hydrazinecarboxylate (800 mg, 2.66 mmol) in dichloromethane (30 mL) was added with sodium hydrogen carbonate (450 mg, 5.40 mmol) and chloroacetic acid chloride (300 mg, 2.66 mmol) were added at 0° C., and the resultant was stirred at room temperature for 3 hours. The reaction solution was added with water and extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate, concentrated in vacuo, and benzyl 2-(2-chloroacetyl)-2-(adamantan-2-yl)hydrazinecarboxylate (726 mg, 72.4%) was obtained as a white crystalline powder.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C:16]2[CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12][C:11]=2[CH:10]=[C:9]1[CH2:24][O:25][Si](C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].F.C(OCC)(=O)C>N1C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[C:16]2[CH2:15][CH2:14][N:13]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:12][C:11]=2[CH:10]=[C:9]1[CH2:24][OH:25])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCc2c(cc(CO[Si](c3ccccc3)(c3ccccc3)C(C)(C)C)n2C(=O)OC(C)(C)C)C1
Agent: F
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N1CCc2c(cc(CO)n2C(=O)OC(C)(C)C)C1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 1,5-bis(t-butoxycarbonyl)-2-(t-butyldiphenylsiloxy)methyl-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine (2.10 g) in pyridine (20 ml), a mixture of hydrogen fluoride and pyridine was added at 0° C., followed by stirring at room temperature for 1 hour. After the reaction mixture was poured into ethyl acetate (50 ml) and ice water (300 ml) which had been stirred in advance, the resulting mixture was separated. The water layer was extracted with ethyl acetate (50 ml). The organic layers were combined, washed with a saturated aqueous solution of sodium bicarbonate, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue thus obtained was purified by chromatography on a silica gel column (150 g of silica gel, hexane:ethyl acetate=3:1), whereby the title compound (882 mg) was obtained as a colorless, transparent caramel-like substance.
Reaction SMILES: [H-].[Na+].[CH3:3][NH:4][C:5](=[O:14])[O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.CS(O[CH2:20][C@H:21]1[CH2:26][O:25][CH2:24][CH2:23][O:22]1)(=O)=O>CN(C)C=O.C(OCC)C>[O:22]1[CH2:23][CH2:24][O:25][CH2:26][C@@H:21]1[CH2:20][N:4]([CH3:3])[C:5](=[O:14])[O:6][CH2:7][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: CNC(=O)OCc1ccccc1
Reactant: CS(=O)(=O)OC[C@H]1COCCO1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOCC
Product: CN(C[C@H]1COCCO1)C(=O)OCc1ccccc1
Temperature: 0 °C
Reaction time: 0.33 h

Procedure:
Sodium hydride (29 mg, 0.74 mmol) was suspended in 2 mL of N,N-dimethylformamide (DMF) and cooled to 0° C. A solution of benzyl methylcarbamate (81 mg, 0.49 mmol) in 2 mL of DMF was added via syringe. After 20 minutes, a solution of (2R)-1,4-dioxan-2-ylmethyl methanesulfonate (191 mg, 0.97 mmol) in 2 mL of DMF was added by syringe and the mixture was heated to 70° C. After 2 h the mixture was cooled to ambient temperature, then diluted in diethyl ether, washed with water and brine, then dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (silica, ethylacetate/hexanes) to afford the title compound. LRMS (APCI) calc'd for (C14H20NO4) [M+H]+, 266.1; found, 266.2.
Reaction SMILES: [CH:1]1([CH2:7][C@H:8]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[C@@H:9]2[CH2:11][O:10]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[NH4+:21]>CO>[NH2:21][CH2:11][C@H:9]([OH:10])[C@@H:8]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH2:7][CH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CC(C)(C)OC(=O)N[C@@H](CC1CCCCC1)[C@@H]1CO1
Reactant: [NH4+]
Agent: [OH-]
Solvent: CO
Product: CC(C)(C)OC(=O)N[C@@H](CC1CCCCC1)[C@@H](O)CN
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a stirred solution of tert-butyl (S)-2-cyclohexyl-1-((R)-oxiran-2-yl)ethylcarbamate (0.20 g, 0.74 mmol) in MeOH (15 mL) at rt, ammonium hydroxide (5 mL) was added. The resulting clear solution was stirred at rt overnight, and completion of reaction was confirmed by LC-MS. Solvent was removed under vacuum to leave tert-butyl (2S,3S)-4-amino-1-cyclohexyl-3-hydroxybutan-2-ylcarbamate (0.21 g, quant.), which was used for the next step without purification; M/S m/z 287 (M+H+).
Reaction SMILES: [CH3:1][CH2:2][N:3]([CH2:6][CH2:7][NH:8][C:9]([C:11]1[CH:12]=[C:13]([Cl:20])[C:14]([NH2:19])=[CH:15][C:16]=1[O:17][CH3:18])=[O:10])[CH2:4][CH3:5].C(N(CC)CC)C.[Cl:28][C:29]1[CH:41]=[CH:40][C:32]([O:33][C:34]([CH3:39])([CH3:38])[C:35](Cl)=[O:36])=[CH:31][CH:30]=1.[OH-].[Na+]>O.C(Cl)(Cl)Cl>[Cl:28][C:29]1[CH:41]=[CH:40][C:32]([O:33][C:34]([CH3:38])([CH3:39])[C:35]([NH:19][C:14]2[C:13]([Cl:20])=[CH:12][C:11]([C:9]([NH:8][CH2:7][CH2:6][N:3]([CH2:2][CH3:1])[CH2:4][CH3:5])=[O:10])=[C:16]([O:17][CH3:18])[CH:15]=2)=[O:36])=[CH:31][CH:30]=1
Reactant: CC(C)(Oc1ccc(Cl)cc1)C(=O)Cl
Reactant: CCN(CC)CCNC(=O)c1cc(Cl)c(N)cc1OC
Agent: [Na+]
Agent: [OH-]
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Solvent: O
Product: CCN(CC)CCNC(=O)c1cc(Cl)c(NC(=O)C(C)(C)Oc2ccc(Cl)cc2)cc1OC
Yield: 73.7 %

Procedure:
Metoclopramide (59.8 g.; 0.2 mole) and triethylamine (30.0 g; 0.3 mole) are dissolved in 400 ml. of chloroform. To this mixture there is added dropwise 2-(4-chlorphenoxy)-2-methylpropionic acid chloride (72.0 g.; 0.3 mole). The mixture is heated under reflux for two hours and is subsequently mixed with 100 ml. of 20% caustic soda solution and with water. After evaporation, the distillation residue is recrystallized from methanol whereby 73.2 g. (73.7% of theory) of 4-[2-(4-chlorphenoxy)isobutyroylamino]-5-chloro-2-methoxy-N-[2-(diethylamino)-ethyl]benzamide having a melting point of 120°-121° C. is obtained.
Reaction SMILES: [N:1]1([C:7]2[CH:17]=[CH:16][C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:9][CH:8]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.Br[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[N+:26]([O-:28])=[O:27].C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.C(OCC)(=O)C>[N+:26]([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[CH2:19][N:4]1[CH2:3][CH2:2][N:1]([C:7]2[CH:8]=[CH:9][C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:16][CH:17]=2)[CH2:6][CH2:5]1)([O-:28])=[O:27]
Reactant: CCOC(=O)c1ccc(N2CCNCC2)cc1
Reactant: O=[N+]([O-])c1ccccc1CBr
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCOC(=O)c1ccc(N2CCN(Cc3ccccc3[N+](=O)[O-])CC2)cc1

Procedure:
Ethyl 4-(piperazin-1-yl)benzoate (1.5 g), 1-(bromomethyl)-2-nitrobenzene (1.383 g) and sodium carbonate (2.036 g) were suspended in anhydrous N,N-dimethylformamide (20 mL) at room temperature for 4 hours. The reaction mixture was diluted with ethyl acetate, washed with water and brine, and concentrated. The residue was purified by flash column purification with 10-40% ethyl acetate/hexane to afford the title compound.
Reaction SMILES: O[Li].O.C[O:5][C:6]([C:8]1[CH:9]=[C:10]([O:14][NH2:15])[CH:11]=[CH:12][CH:13]=1)=[O:7].C1COCC1.CO.O.Cl>O>[C:6]([C:8]1[CH:9]=[C:10]([O:14][NH2:15])[CH:11]=[CH:12][CH:13]=1)([OH:7])=[O:5]
Reactant: COC(=O)c1cccc(ON)c1
Agent: Cl
Agent: [Li]O
Solvent: CO
Solvent: O
Solvent: C1CCOC1
Product: NOc1cccc(C(=O)O)c1
Temperature: 25 °C
Yield: 95 %

Procedure:
LiOH.H2O (91.0 mg, 2.17 mmol) was added to a solution of O-(3-methoxycarbonyl-phenyl)hydroxylamine 14 (90.4 mg, 0.541 mmol) in a 3/1/1 mL mixture of THF/MeOH/H2O and the reaction was stirred at room temperature. After 24 h the reaction was diluted with H2O (50 mL), acidified to pH-3-4 with 0.5 N HCl, and extracted with EtOAc (3×25 mL). The combined organics were washed with H2O (25 mL) and brine (25 mL), dried over Na2SO4, filtered, and concentrated to afford 3 as a white solid (78.7 mg, 95%). 1H-NMR (500 MHz, d6-DMSO) δ 7.01 (s, 2H), 7.24 (ddd, J=1.4, 2.8, 8.3 Hz, 1H), 7.34 (t, J=7.8 Hz, 1H), 7.46 (dt, J=1.4, 7.3 Hz, 1H), 7.68 (dd, J=1.4, 2.8 Hz, 1H); 13C-NMR (125 MHz, d6-DMSO) δ 113.5, 117.8, 121.3, 129.2, 131.8, 161.7, 167.3; ESI-MS 162 m/z [M-H+]−, C7H6NO3 requires 162.
Reaction SMILES: [C:1]([O:9][C@H:10]1[C@@H:16]([O:17][C:18](=[O:25])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C@H:15]([CH2:26][O:27][C:28](=[O:35])[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[O:14][CH:11]1OC)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O=C[C@H]([C@H]([C@H](CO)O)O)O.C(OC(=O)C)(=O)C.[C:53]([OH:56])(=[O:55])[CH3:54].S(=O)(=O)(O)O>O>[C:53]([O:56][CH:11]1[O:14][C@@H:15]([CH2:26][O:27][C:28](=[O:35])[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C@H:16]([O:17][C:18](=[O:25])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C@@H:10]1[O:9][C:1](=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)(=[O:55])[CH3:54]
Reactant: CC(=O)O
Reactant: COC1O[C@@H](COC(=O)c2ccccc2)[C@H](OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1
Agent: O=C[C@@H](O)[C@@H](O)[C@@H](O)CO
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CC(=O)OC(C)=O
Product: CC(=O)OC1O[C@@H](COC(=O)c2ccccc2)[C@H](OC(=O)c2ccccc2)[C@@H]1OC(=O)c1ccccc1

Procedure:
5.37 g of crude 2,3,5-tri-O-benzoyl-1-O-methyl-L-ribofuranose synthesized from L-ribose (1.0 g; 6.66 mmol) in accordance with the method described in Helvetica Chimica Acta 1959, (121), 1171-1173p was added to a 100-ml flask. Thereafter, acetic anhydride (3.73 ml; 5.95 equivalents) and acetic acid (1.60 ml; 2.80 equivalents) were added thereto. The obtained mixture was cooled on ice, and thereafter, concentrated sulfuric acid (530 μl; 1.5 equivalents) was slowly added dropwise thereto. After completion of the reaction for 30 minutes, cold water (50 ml) was slowly added dropwise to the reaction solution, and an upper aqueous layer was separated. The precipitated semi-oily solid was dried under reduced pressure. Thus, 3.97 g of crude 1-O-acetyl-2,3,5-tri-O-benzoyl-L-ribofuranose was obtained in the form of a light yellow oily solid. The obtained solid was analyzed by HPLC. As a result, the ratio of α-/β-anomers in the crude 1-O-acetyl-2,3,5-tri-O-benzoyl-L-ribofuranose was 35/65, and the reaction yield of the β-anomer from the total 3 steps was 56%.