Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[NH2:2][CH2:3][CH:4]([C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:16][CH3:17])[CH:14]=2)[CH:9]=[CH:8][CH:7]=1)[OH:5].C(=O)([O-])[O-].[K+].[K+].[C:24](Cl)(=[O:26])[CH3:25]>O.C(OCC)(=O)C>[OH:5][CH:4]([C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:16][CH3:17])[CH:14]=2)[CH:9]=[CH:8][CH:7]=1)[CH2:3][NH:2][C:24](=[O:26])[CH3:25]
Reactant: COc1ccc2cccc(C(O)CN)c2c1
Reactant: CC(=O)Cl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: O
Product: COc1ccc2cccc(C(O)CNC(C)=O)c2c1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
The compound obtained in Step E (20 mmol) is dissolved in a mixture of water/ethyl acetate (25 ml/75 ml) cooled to 0° C. Potassium carbonate (60 mmol) is added, and then acetyl chloride (26 mmol) is added dropwise to the reaction mixture. The mixture is stirred vigorously for 30 minutes at ambient temperature. The two phases are separated and the organic phase is washed with 0.1M aqueous hydrochloric acid solution and then with water. After drying over magnesium sulphate, the organic phase is evaporated under reduced pressure. The residue obtained is recrystallised from acetonitrile to yield the title product in the form of a white solid.
Reaction SMILES: [CH:1]([C:4]1[C:11]([O:12][CH3:13])=[CH:10][CH:9]=[CH:8][C:5]=1[CH:6]=O)([CH3:3])[CH3:2].[N+:14]([CH3:17])([O-:16])=[O:15].C([O-])(=O)C.[NH4+]>C(O)(=O)C>[CH:1]([C:4]1[C:5]([CH:6]=[CH:17][N+:14]([O-:16])=[O:15])=[CH:8][CH:9]=[CH:10][C:11]=1[O:12][CH3:13])([CH3:3])[CH3:2]
Reactant: COc1cccc(C=O)c1C(C)C
Reactant: C[N+](=O)[O-]
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: CC(=O)O
Product: COc1cccc(C=C[N+](=O)[O-])c1C(C)C
Yield: 88.6 %

Procedure:
Using a method similar to Example 659, Step 1, using 2-isopropyl-3-methoxy-benzaldehyde (3.56 g, 20.0 mmol), nitromethane (3.25 ml, 60.0 mmol), ammonium acetate (2.00 g, 26.0 mmol) and acetic acid (25 ml) gave 2-isopropyl-1-methoxy-3-(2-nitro-vinyl)-benzene (3.92 g) as a viscous oil. 1HNMR (CDCl3): 8.48 (d, 1H), 7.38 (d, 1H), 7.20 (t, 1H), 7.02-6.96 (m, 2H), 3.84 (s, 3H), 3.41 (m, 1H), 1.36 (d, 6H).
Reaction SMILES: [Cl:1][C:2]1[C:10]([F:11])=[C:9]2[C:5]([CH:6]=[C:7](C(O)=O)[NH:8]2)=[CH:4][CH:3]=1>C1(OC2C=CC=CC=2)C=CC=CC=1>[Cl:1][C:2]1[C:10]([F:11])=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][CH:3]=1
Reactant: O=C(O)c1cc2ccc(Cl)c(F)c2[nH]1
Solvent: c1ccc(Oc2ccccc2)cc1
Product: Fc1c(Cl)ccc2cc[nH]c12
Temperature: 25 °C
Yield: 62.6 %

Procedure:
A solution of 6-chloro-7-fluoroindole-2-carboxylic acid (2.1 g, 9.8 mmol) and diphenyl ether (30 mL) was heated under reflux for 4 h, cooled to room temperature and purified by column chromatography [SiO2; heptane-ethyl acetate (99:1 to 10:1)] to give the product (1.04 g, 63% yield) as a pale brown oil: IR νmax (Nujol)/cm−1 3460, 1573, 1490, 1446, 1201, 802 and 619; NMR δH (400 MHz, CDCl3) 6.44 (1H, brs) 7.04-7.09 (1H, m) 7.21-7.26 (1H, m) 7.30-7.34 (1H, m) and 8.40 (1H, brs).
Reaction SMILES: C[O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=[O:15])[CH2:10][CH2:11][C:12]([OH:14])=[O:13])=[CH:5][CH:4]=1.[CH2:16](O)[CH3:17]>Br.C(O)(=O)C>[CH2:16]([O:14][C:12](=[O:13])[CH2:11][CH2:10][C:9]([C:6]1[CH:7]=[CH:8][C:3]([OH:2])=[CH:4][CH:5]=1)=[O:15])[CH3:17]
Reactant: CCO
Reactant: COc1ccc(C(=O)CCC(=O)O)cc1
Agent: Br
Solvent: CC(=O)O
Product: CCOC(=O)CCC(=O)c1ccc(O)cc1

Procedure:
In a 1 L round bottom flask, 4-(4-methoxyphenyl)-4-oxo-butyric acid (25 g, 106 mmol) in 48% HBr (125 mL) and acetic acid (250 mL) was heated to reflux 18 h. The reaction was cooled slightly and ethanol (250 mL) was added. The solvent was concentrated under vacuum. Additional ethanol (100 mL) was added and solvent concentrated under vacuum again. The resulting oil was crystallized from ethyl acetate/hexanes to produce 8.65 g (37%). MS m/z=223 (M+H).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][C:12](=[O:14])[O:11][C@H:10]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C@@H:9]1[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:27]1([C:31]2[CH:32]=[C:33]([CH:36]=[CH:37][CH:38]=2)[CH2:34]Br)[CH2:30][CH2:29][CH2:28]1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1>[O:14]=[C:12]1[C@H:13]([CH2:34][C:33]2[CH:36]=[CH:37][CH:38]=[C:31]([CH:27]3[CH2:28][CH2:29][CH2:30]3)[CH:32]=2)[N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[C@@H:9]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C@@H:10]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[O:11]1
Reactant: CC(C)(C)OC(=O)N1CC(=O)O[C@H](c2ccccc2)[C@@H]1c1ccccc1
Reactant: BrCc1cccc(C2CCC2)c1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1[C@@H](Cc2cccc(C3CCC3)c2)C(=O)O[C@H](c2ccccc2)[C@@H]1c1ccccc1
Yield: 54.1 %

Procedure:
According to example 81, 2.50 g of tert-butyl- (2R, 3S)-(-)-6-oxo-2,3-diphenyl-4-morpholinecarboxylate (Aldrich) was alkylated with 1.59 g of 3-cyclobutylbenzyl bromide in 80 mL of anhydrous THF using 7.41 mL of 1M sodium bis(trimethylsilyl)amide in THF (Aldrich). The crude product was subjected to flash chromatography on 120 g of silica gel (8:2 hexane:EtOAc) and then recrystallization from EtOH-water to afford 1.90 g (54%) of tert-butyl (2R, 3S, 5S)-6-oxo-2,3-diphenyl-5-(3-cyclobutylbenzyl)-4-morpholinecarboxylate as a white powder, m.p. 145-147° C.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([CH2:13][O:12][C:11]3[CH:14]=[C:15]4[C:19](=[CH:20][C:10]2=3)[CH2:18][CH2:17][O:16]4)[C:2]1=[O:21].CC1C2C=C3C4(C5C(=CC=CC=5)NC4=O)COC3=CC=2ON=1.Cl[CH2:45][C:46]1[CH:51]=[N:50][CH:49]=[CH:48][N:47]=1.BrCC1OC(C(F)(F)F)=CC=1>>[N:47]1[CH:48]=[CH:49][N:50]=[CH:51][C:46]=1[CH2:45][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([CH2:13][O:12][C:11]3[CH:14]=[C:15]4[C:19](=[CH:20][C:10]2=3)[CH2:18][CH2:17][O:16]4)[C:2]1=[O:21]
Reactant: ClCc1cnccn1
Reactant: O=C1Nc2ccccc2C12COc1cc3c(cc12)CCO3
Agent: Cc1noc2cc3c(cc12)C1(CO3)C(=O)Nc2ccccc21
Agent: FC(F)(F)c1ccc(CBr)o1
Product: O=C1N(Cc2cnccn2)c2ccccc2C12COc1cc3c(cc12)CCO3

Procedure:
Following the procedure as described in EXAMPLE 9 and making non-critical variations using 5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1′H)-one to replace 3-methylspiro[furo[3,2-f][1,2]benzisoxazole-5,3′-indol]-2′(1′H)-one, and 2-(chloromethyl)pyrazine to replace 2-(bromomethyl)-5-(trifluoromethyl)furan, 1′-(pyrazin-2-ylmethyl)-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1′H)-one was obtained (27%) as a colorless solid: mp 143-144° C.; 1H NMR (300 MHz, CDCl3) δ8.64 (br s, 1H), 8.58-8.59 (m, 2H), 7.24-7.17 (m, 2H), 7.09-7.02 (m, 1H), 6.91-6.86 (m, 1H), 6.54 (s, 1H), 6.43 (s, 1H), 5.14 (ABq, 2H), 4.85 (ABq, 2H), 4.59-4.50 (m, 2H), 3.10-2.91 (m, 2H); 13C NMR (75 MHz, CDCl3) δ177.9, 161.9, 161.3, 151.4, 144.2, 143.9, 143.8, 141.6, 132.7, 128.8, 124.0, 123.8, 120.0, 119.9, 119.0, 109.1, 93.2, 80.6, 72.4, 57.8, 43.8, 29.0; MS (ES+) m/z 372.3 (M+1).
Reaction SMILES: [CH3:1][S:2]([NH:5][C@@H:6]([C:10]([CH3:13])([CH3:12])[CH3:11])[C:7](O)=[O:8])(=[O:4])=[O:3].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.[CH2:42]([NH:49][NH2:50])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.CCN(CC)CC>>[CH2:42]([NH:49][NH:50][C:7]([C@@H:6]([NH:5][S:2]([CH3:1])(=[O:4])=[O:3])[C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1
Reactant: CC(C)(C)[C@H](NS(C)(=O)=O)C(=O)O
Reactant: NNCc1ccccc1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CN1CCOCC1
Solvent: CCN(CC)CC
Product: CC(C)(C)[C@H](NS(C)(=O)=O)C(=O)NNCc1ccccc1
Yield: 58 %

Procedure:
A solution of methanesulfonyl chloride (0.593 mL, 7.62 mmol) in 1M NaOH (7.60 mL, 15.2 mmol) and THF (10 mL) was added drop wise to a stirred mixture of (L)-tert-leucine (1.0 g, 7.6 mmol), dissolved in THF (7.6 mL) and H2O (12 mL) at 0° C. The reaction mixture was stirred at 0° C. for 3 h and then at room temperature overnight. The mixture was acidified with 4M HCl and extracted with EtOAc. The organic phase was separated, dried (Na2SO4), filtered and concentrated under reduced pressure to give (2S)-2-methanesulphonylamino-3,3-dimethyl-butyric acid (0.486 g, 30%), which was analyzed by NMR and then used without further purification. The general procedure for the preparation of hydrazides described above was then followed using the crude (2S)-2-methanesulfonylamino-3,3-dimethyl-butyric acid (0.476 g, 2.27 mmol), EDAC (0.481 g, 2.51 mmol), HOBT (0.338 g, 2.50 mmol), NMM (0.275 mL, 2.50 mmol), benzylhydrazine×2HCl (0.489 g, 2.51 mmol) and Et3N (0.700 mL, 4.98 mmol) which gave the title compound (0.416 g, 58%) as a white solid.
Reaction SMILES: [CH:1]([C:3]1[N:7]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[CH:10][CH:9]=2)[CH:6]=[N:5][CH:4]=1)=O.[CH3:16][NH:17][CH2:18][CH2:19][NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClCCCl>[C:12]([C:11]1[CH:14]=[CH:15][C:8]([N:7]2[C:3]([CH2:1][N:17]([CH3:16])[CH2:18][CH2:19][NH:20][C:21](=[O:27])[O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[CH:4][N:5]=[CH:6]2)=[CH:9][CH:10]=1)#[N:13]
Reactant: N#Cc1ccc(-n2cncc2C=O)cc1
Reactant: CNCCNC(=O)OC(C)(C)C
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCCl
Product: CN(CCNC(=O)OC(C)(C)C)Cc1cncn1-c1ccc(C#N)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 90.4 %

Procedure:
To a solution of 4-(5-formyl-1H-imidazol-1-yl)benzonitrile (55 mg, 0.28 mmol, 1.00 equiv) and tert-butyl N-[2-(methylamino)ethyl]carbamate (58 mg, 0.33 mmol, 1.19 equiv) in 1,2-dichloroethane (20 mL) was added NaBH(OAc)3 (178 mg, 0.82 mmol, 2.95 equiv). The reaction was stirred at room temperature for 2 h and then concentrated under vacuum. The residue was purified on a silica gel column eluted with 0-5.4% of methanol in dichloromethane to give 90 mg (91%) of tert-butyl 2-(((1-(4-cyanophenyl)-1H-imidazol-5-yl)methyl)(methyl)amino)ethylcarbamate as a colorless oil. LCMS (method D, ESI): RT=0.98 min, m/z=356.0 [M+H]+.
Reaction SMILES: [N:1]1([CH2:7][CH2:8][N:9]2[C:17]3[C:12](=[CH:13][C:14]([N+:18]([O-])=O)=[CH:15][CH:16]=3)[CH:11]=[N:10]2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[Cl-].[NH4+]>[Fe].C(O)C.O>[N:1]1([CH2:7][CH2:8][N:9]2[C:17]3[C:12](=[CH:13][C:14]([NH2:18])=[CH:15][CH:16]=3)[CH:11]=[N:10]2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1
Reactant: O=[N+]([O-])c1ccc2c(cnn2CCN2CCOCC2)c1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Solvent: O
Product: Nc1ccc2c(cnn2CCN2CCOCC2)c1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 86.3 %

Procedure:
A mixture of 1-(2-morpholin-4-yl-ethyl)-5-nitro-1H-indazole (4.3 g, 16 mmol), iron powder (8.8 g, 157 mmol), and ammonium chloride (430 mg, 8 mmol) in a 4:1 ethanol/H2O solution (75 mL) was heated to reflux for 3 hours, cooled to room temperature and concentrated under reduced pressure. The residue was taken up and stirred in triethylamine/ethyl acetate (1/4, 50 mL) for 15 minutes, filtered through a plug of silica gel and rinsed with triethylamine/ethyl acetate (1/4). The filtrate was concentrated under reduced pressure to provide the title compound (3.4 g, 93%). 1H NMR (300 MHz, DMSO-d6) ppm 2.40 (t, J=4.75, 4H), 2.70 (t, J=6.78, 2H), 3.50 (t, J=4.75, 4H), 4.38 (t, J=6.78, 2H), 4.78 (s, 2H), 6.72 (m, 1H), 6.80 (m, 1H), 7.35 (m, 1H), 7.60 (m, 1H); MS (DCI/NH3) m/z 247 [M+H]+.
Reaction SMILES: [Cl-:1].[NH4+].[CH2:3]([O:5][C:6]1[C:14]([N+:15]([O-])=O)=[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][N:8]2[N:7]=1)[CH3:4]>>[ClH:1].[ClH:1].[ClH:1].[CH2:3]([O:5][C:6]1[C:14]([NH2:15])=[C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][N:8]2[N:7]=1)[CH3:4]
Reactant: [Cl-]
Reactant: CCOc1nn2ccccc2c1[N+](=O)[O-]
Agent: [NH4+]
Product: CCOc1nn2ccccc2c1N
Product: Cl

Procedure:
Then 500 mg of ammonium chloride were added and then, in portions, 3.88 g of 2-ethoxy-3-nitropyrazolo[1,5-a]pyridine.
Reaction SMILES: [CH:1]1([OH:9])[CH2:6][CH:5]([OH:7])[CH2:4][CH:3]([OH:8])[CH2:2]1.[CH:10]1([C:16](Cl)=[O:17])[CH2:15][CH2:14][CH:13]=[CH:12][CH2:11]1.Cl>N1C=CC=CC=1>[CH:10]1([C:16]([O:7][CH:5]2[CH2:6][CH:1]([O:9][C:16]([CH:10]3[CH2:15][CH2:14][CH:13]=[CH:12][CH2:11]3)=[O:17])[CH2:2][CH:3]([O:8][C:16]([CH:10]3[CH2:15][CH2:14][CH:13]=[CH:12][CH2:11]3)=[O:17])[CH2:4]2)=[O:17])[CH2:15][CH2:14][CH:13]=[CH:12][CH2:11]1
Reactant: O=C(Cl)C1CC=CCC1
Reactant: OC1CC(O)CC(O)C1
Agent: Cl
Solvent: c1ccncc1
Product: O=C(OC1CC(OC(=O)C2CC=CCC2)CC(OC(=O)C2CC=CCC2)C1)C1CC=CCC1
Temperature: 2.5 °C
Reaction time: 4 h
Yield: 100.8 %

Procedure:
To 1.32 g (10 mmol) of cyclohexane-1,3,5-triol (a mixture of cis- and trans-isomers) dissolved in 20 ml of pyridine was added dropwise 6.51 g (45 mmol) of 3-cyclohexene carbonyl chloride within 30 minutes at 5° C. or lower, followed by stirring at 0 to 5° C. for 4 hours to allow the reaction to proceed. After the reaction, the reaction solution was poured into a mixture of 50 ml of 10% hydrochloric acid and 50 ml of ice water, and the resultant was extracted with 30 ml of chloroform three times. The combined organic layers were washed twice with 30 ml of saturated sodium bicarbonate solution and then with 30 ml of saturated sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give 4.6 g of the desired 1,3,5-tris(3-cyclohexene carbonyloxy)cyclohexane as a pale yellow oil.
Reaction SMILES: Br[C:2]1[C:11]([N:12]2[C:21]3[C:16](=[CH:17][C:18]([F:22])=[CH:19][CH:20]=3)[CH2:15][CH2:14][CH2:13]2)=[N:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:23]([O:25][CH3:26])=[O:24])[CH:8]=2)[N:3]=1.[CH3:27][C:28]1[NH:29][C:30]2[C:35]([CH:36]=1)=[CH:34][C:33](B1OC(C)(C)C(C)(C)O1)=[CH:32][CH:31]=2.C(=O)([O-])[O-].[Na+].[Na+].O>COCCOC.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>[F:22][C:18]1[CH:17]=[C:16]2[C:21](=[CH:20][CH:19]=1)[N:12]([C:11]1[C:2]([C:33]3[CH:34]=[C:35]4[C:30](=[CH:31][CH:32]=3)[NH:29][C:28]([CH3:27])=[CH:36]4)=[N:3][C:4]3[C:9]([N:10]=1)=[CH:8][C:7]([C:23]([O:25][CH3:26])=[O:24])=[CH:6][CH:5]=3)[CH2:13][CH2:14][CH2:15]2
Reactant: Cc1cc2cc(B3OC(C)(C)C(C)(C)O3)ccc2[nH]1
Reactant: COC(=O)c1ccc2nc(Br)c(N3CCCc4cc(F)ccc43)nc2c1
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: O
Solvent: COCCOC
Product: COC(=O)c1ccc2nc(-c3ccc4[nH]c(C)cc4c3)c(N3CCCc4cc(F)ccc43)nc2c1
Temperature: 90 °C
Reaction time: 0.67 h
Yield: 52.7 %

Procedure:
To a solution of methyl 2-bromo-3-(6-fluoro-1,2,3,4-tetrahydroquinolin-1-yl)quinoxaline-6-carboxylate (200 mg, 0.48 mmol) in ethylene glycol dimethyl ether (7 ml) was added 2-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (124 mg, 0.48 mmol), sodium carbonate (101.8 mg, 0.96 mmol) and Pd(PPh3)4 (28 mg, 0.02 mmol) and water (3 ml). The reaction was stirred for 40 min at 90° C. Then it was extracted with ethyl acetate (3×50 ml) and the organic layers were combined, dried over anhydrous magnesium sulfate and concentrated in vacuo to provide a residue, which was purified by a silica gel column chromatography with 2% ethyl acetate in petroleum ether to afford methyl 3-(6-fluoro-1,2,3,4-tetrahydroquinolin-1-yl)-2-(2-methyl-1H-indol-5-yl)quinoxaline-6-carboxylate as a light red solid (118 mg, 53%).
Reaction SMILES: [CH2:1]([C@@H:8](/[CH:24]=[CH:25]/[CH2:26][C:27]([N:29]1[C@@H:33]([CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:32][O:31][C:30]1=[O:41])=[O:28])[C:9]([N:11]1[C@@H:15]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:14][O:13][C:12]1=[O:23])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:42][Si]([N-][Si](C)(C)C)(C)C.[Na+].CI.[NH4+].[Cl-]>C1COCC1>[CH2:1]([C@@H:8](/[CH:24]=[CH:25]/[C@H:26]([CH3:42])[C:27]([N:29]1[C@@H:33]([CH2:34][C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH2:32][O:31][C:30]1=[O:41])=[O:28])[C:9]([N:11]1[C@@H:15]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:14][O:13][C:12]1=[O:23])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Reactant: O=C(C/C=C/[C@H](Cc1ccccc1)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1)N1C(=O)OC[C@@H]1Cc1ccccc1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CI
Solvent: C1CCOC1
Product: C[C@@H](/C=C/[C@H](Cc1ccccc1)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1)C(=O)N1C(=O)OC[C@@H]1Cc1ccccc1
Temperature: -78 °C
Reaction time: 1 h
Yield: 54 %

Procedure:
To a solution of (S,E)-2-benzyl-1,6-bis((S)-4-benzyl-2-oxooxazolidin-3-yl)hex-3-ene-1,6-dione (250 mg, 0.450 mmol) in THF (50 mL) at −78° C., a solution of NaHMDS (1 M in THF, 0.54 mL, 0.54 mmol) in diluted in THF (2.5 mL) was added dropwise. The reaction mixture was stirred for 1 hr at −78° C. and then methyl iodide (0.078 g, 0.55 mmol) was added in two portions. The reaction mixture was warmed to rt and allowed to stir overnight. Saturated aqueous NH4Cl (3 mL) was added to the reaction mixture and crude product was extracted with ethyl acetate (5 mL). The organic layer was separated, dried (Na2SO4) and concentrated to afford crude product, which was purified using silica gel chromatography to afford (2S,5S,E)-2-benzyl-1,6-bis((S)-4-benzyl-2-oxooxazolidin-3-yl)-5-methylhex-3-ene-1,6-dione (137 mg, 0.243 mmol, 54% yield). Anal. Calcd. for C34H34N2O6 m/z 566.2. found 565.2 (M−): 1H NMR (400 MHz, CDCl3) δ ppm 7.36-7.30 (m, 5H), 7.29-7.26 (m, 5H), 7.25-7.18 (m, 3H), 7.08-7.05 (m, 2H), 5.75-5.62 (m, 2H), 4.72-4.57 (m, 3H), 4.36-4.29 (m, 1H), 4.23-4.12 (m, 4H), 3.28-3.21 (m, 2H), 3.10 (m, 1H), 2.84 (m, 1H), 2.76 (m, 1H), 2.61 (m, 1H), 1.24 (d, J=6.8 Hz, 3H).
Reaction SMILES: [OH:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@H:4]([CH2:15][O:16][Si:17]([CH:24]([CH3:26])[CH3:25])([CH:21]([CH3:23])[CH3:22])[CH:18]([CH3:20])[CH3:19])[CH2:3]1.C[N+]1([O-])CCOCC1>ClCCl.[Ru]([O-])(=O)(=O)=O.C([N+](CCC)(CCC)CCC)CC>[O:1]=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@H:4]([CH2:15][O:16][Si:17]([CH:18]([CH3:20])[CH3:19])([CH:21]([CH3:23])[CH3:22])[CH:24]([CH3:25])[CH3:26])[CH2:3]1
Reactant: CC(C)[Si](OC[C@@H]1CC(O)CCN1C(=O)OC(C)(C)C)(C(C)C)C(C)C
Agent: O=[Ru](=O)(=O)[O-]
Agent: CCC[N+](CCC)(CCC)CCC
Agent: C[N+]1([O-])CCOCC1
Solvent: ClCCl
Product: CC(C)[Si](OC[C@@H]1CC(=O)CCN1C(=O)OC(C)(C)C)(C(C)C)C(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of Example 260B (3.32 g, 8.56 mmol) in dichloromethane (28.5 mL) was added activated powdered 4 Å molecular sieves (9 g), tetrapropylammonium perruthenate (0.150 g, 0.428 mmol) and N-methylmorpholine-N-oxide (1.505 g, 12.85 mmol), and the mixture was stirred overnight at room temperature. The mixture was filtered through a pad of silica, rinsing with ethyl acetate. The filtrate was concentrated and purified by flash chromatography on silica gel (gradient from 0-20% ethyl acetate-heptanes) to give the title compound. MS (ESI+) m/z 385.8 (M+H)+.
Reaction SMILES: [CH:1]([O:4][NH:5][C:6](=O)[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([CH2:13][CH2:14][CH:15]([CH3:17])[CH3:16])[CH:8]=1)([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)(Cl)(Cl)[Cl:39]>C(#N)C>[CH:1]([O:4][N:5]=[C:6]([Cl:39])[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([CH2:13][CH2:14][CH:15]([CH3:17])[CH3:16])[CH:8]=1)([CH3:3])[CH3:2]
Reactant: CC(C)CCc1cccc(C(=O)NOC(C)C)c1
Reactant: ClC(Cl)(Cl)Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CC#N
Product: CC(C)CCc1cccc(C(Cl)=NOC(C)C)c1
Yield: 88 %

Procedure:
To 200 ml of acetonitrile were added 5.4 g (23.5 mmol) of O-isopropyl 3-isopentylbenzohydroxamic acid, 9.9 g (37.8 mmol) of triphenylphosphine, and 11.6 g (75.3 mmol) of carbon tetrachloride. The mixture was refluxed for 1 hour. The refluxed mixture was allowed to sit and cool naturally, and the solvent in the mixture was removed under reduced pressure. The residue was purified by column chromatography, thus obtaining the desired product of 5.1 g (yield: 88% ).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([O:41][CH3:42])=[CH:5][C:6]2[CH2:12][CH2:11][CH2:10][C:9]([C:13]([N:15]3[CH2:20][CH2:19][N:18]([C:21](=[O:34])[C:22]4[CH:27]=[C:26]([O:28][CH3:29])[C:25]([O:30][CH3:31])=[C:24]([O:32][CH3:33])[CH:23]=4)[CH2:17][CH:16]3[C:35]([O:37]CC)=[O:36])=[O:14])=[CH:8][C:7]=2[CH:40]=1.C(=O)([O-])[O-].[K+].[K+].O>CO>[CH3:1][O:2][C:3]1[C:4]([O:41][CH3:42])=[CH:5][C:6]2[CH2:12][CH2:11][CH2:10][C:9]([C:13]([N:15]3[CH2:20][CH2:19][N:18]([C:21](=[O:34])[C:22]4[CH:27]=[C:26]([O:28][CH3:29])[C:25]([O:30][CH3:31])=[C:24]([O:32][CH3:33])[CH:23]=4)[CH2:17][CH:16]3[C:35]([OH:37])=[O:36])=[O:14])=[CH:8][C:7]=2[CH:40]=1
Reactant: CCOC(=O)C1CN(C(=O)c2cc(OC)c(OC)c(OC)c2)CCN1C(=O)C1=Cc2cc(OC)c(OC)cc2CCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: COc1cc2c(cc1OC)CCCC(C(=O)N1CCN(C(=O)c3cc(OC)c(OC)c(OC)c3)CC1C(=O)O)=C2
Temperature: 70 °C
Reaction time: 0.5 h
Yield: 96.3 %

Procedure:
To a solution of ethyl 1-(2,3-dimethoxy-6,7-dihydro-5H-benzocyclohepten-8-ylcarbonyl) -4-(3,4,5-trimethoxybenzoyl)piperazine-2-carboxylate (1.2 g) in methanol (15 ml) are added potassium carbonate (3.0 g) and water (8 ml) and the mixture is stirred at 70° C. for 30 minutes. To the reaction mixture is added water (50 ml). The mixture is washed with ethyl acetate. The aqueous layer is made acid with dilute hydrochloric acid, followed by extraction with ethyl acetate. The organic layer is washed with water, dried and concentrated under reduced pressure to give a crude product of 1-(2,3-dimethoxy-6,7-dihydro-5H-benzocyclohepten-8-ylcarbonyl) -4-(3,4,5-trimethoxybenzoyl)piperazine-2-carboxylic acid (1.1 g) as a colorless oily substance. To a mixture of this crude product (0.75 g), triethylamine (0.14 g) and N,N-dimethylformamide (4 ml) is added dropwise, while stirring under ice-cooling, diphenylphosphoryl azide (0.37 g). The reaction mixture is poured into ice-water, followed by extraction with benzene. The organic layer is washed with water and dried, followed by distilling off the solvent under reduced pressure until the whole volume becomes about 20 ml. The resultant solution is heated under reflux for 30 minutes. To the mixture is added methanol (5 ml), followed by heating under reflux for further one hour. The reaction mixture is concentrated under reduced pressure, and the concentrate is purified by means of a silica gel column chromatography (eluent hexane ethyl acetate-acetone=1:1:1) to give crystals, which are recrystallized from ethyl acetate to give 1-(2,3-dimethoxy-6,7-dihydro-5H-benzocyclohepten-8-ylcarbonyl) -2-methoxycarbonylamino-4-(3,4,5-trimethoxybenzoyl)piperazine as colorless crystals (0.6 g), m.p. 143-145° C.
Reaction SMILES: [CH3:1][O:2][CH:3]([O:8][CH3:9])[C:4]([O:6]C)=O.[CH3:10][O:11][C:12]1[CH:13]=[C:14]([CH:17]=[CH:18][CH:19]=1)[CH2:15][NH2:16]>>[CH3:9][O:8][CH:3]([O:2][CH3:1])[C:4]([NH:16][CH2:15][C:14]1[CH:17]=[CH:18][CH:19]=[C:12]([O:11][CH3:10])[CH:13]=1)=[O:6]
Reactant: COc1cccc(CN)c1
Reactant: COC(=O)C(OC)OC
Product: COc1cccc(CNC(=O)C(OC)OC)c1
Temperature: 25 °C
Reaction time: 192 h

Procedure:
Into a vial was added methyl dimethoxyacetate (2.0 g, 14 mmol) and 3-methoxybenzylamine (2.0 g, 14 mmol), this mixture was stirred at room temperature for 8 d. The product was triturated with heptane (3×) and then dried in vacuo, yielding the desired product as an off-white solid. MS (ES+): m/z=240.84 [MH+]. HPLC: tR=2.55 min (ZQ2, polar—5 min).
Reaction SMILES: [NH2:1][C:2]1[C:10]([Br:11])=[C:9]2[C:5]([CH2:6][CH2:7][C:8]2=[O:12])=[CH:4][CH:3]=1.[C:13]1([S:19](Cl)(=[O:21])=[O:20])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>N1C=CC=CC=1.C(Cl)Cl>[Br:11][C:10]1[C:2]([NH:1][S:19]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)(=[O:21])=[O:20])=[CH:3][CH:4]=[C:5]2[C:9]=1[C:8](=[O:12])[CH2:7][CH2:6]2
Reactant: O=S(=O)(Cl)c1ccccc1
Reactant: Nc1ccc2c(c1Br)C(=O)CC2
Solvent: ClCCl
Solvent: c1ccncc1
Product: O=C1CCc2ccc(NS(=O)(=O)c3ccccc3)c(Br)c21
Reaction time: 2 h
Yield: 34.9 %

Procedure:
A solution of Example 129C (1.0808 g, 3.52 mmol) in pyridine (17.5 mL) was treated with phenylsulfonyl chloride (0.58 mL, 4.58 mmol), stirred for 2 hours, diluted with CH2Cl2, washed with 1N HCl (3×50 mL) and brine (50 mL), dried (MgSO4), filtered, and concentrated. The residue was purified by flash column chromatography on silica gel with 9:1 hexanes/ethyl acetate to provide the desired product (450 mg, 35%); MS (ESI(+)) m/e 368 (M+H)+; MS (ESI(−)) m/e 364, 366 (M−H)−; 1H NMR (300 MHz, DMSO-d6) δ 7.70 (m, 2H), 7.63 (m, 1H), 7.56 (m, 2H), 7.51 (m, 1H), 7.42 (m, 1H), 3.00 (m, 2H), 2.66 (m, 2H).