Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[Si](C)(C)N[Si](C)(C)C.[Li]CCCC.CCCCCC.[CH2:21]([O:23][C:24](=[O:31])[CH2:25]/[N:26]=[CH:27]/[N:28]([CH3:30])[CH3:29])[CH3:22].ClC1[CH2:34][N:35]([CH2:46][C:47]2[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][C:48]=2[O:55][CH3:56])[C:36](=[O:45])[C:37]2[CH:43]=[C:42]([Br:44])[CH:41]=[CH:40]C=2N=1>C1COCC1.O.C(O)(=O)C>[CH2:21]([O:23][C:24]([C:25]1[N:26]=[CH:27][N:28]2[C:30]=1[CH2:34][N:35]([CH2:46][C:47]1[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][C:48]=1[O:55][CH3:56])[C:36](=[O:45])[C:37]1[CH:43]=[C:42]([Br:44])[CH:41]=[CH:40][C:29]2=1)=[O:31])[CH3:22]
Reactant: CCOC(=O)C/N=C/N(C)C
Reactant: COc1ccc(CN2CC(Cl)=Nc3ccc(Br)cc3C2=O)c(OC)c1
Agent: C[Si](C)(C)N[Si](C)(C)C
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: CCOC(=O)c1ncn2c1CN(Cc1ccc(OC)cc1OC)C(=O)c1cc(Br)ccc1-2
Temperature: -70 °C
Reaction time: 1 h

Procedure:
Hexamethyldisilazane (5.1 mL, 24.4 mmol) was dissolved in TBF (30 mL), cooled under Argon to −70° C., and treated slowly with a 1.6 M solution of n-BuLi in hexane (14.5 mL, 23.2 mmol). After stirring for 1 h at −70° C., a solution of (E)-(dimethylamino-methyleneamino)-acetic acid ethyl ester (2.34 g, 14.8 mmol) in THF (10 mL) was added, and stirring continued for 1 h at −70° C. Then a solution of 2-chloro-4-(2,4-dimethoxy-benzyl)-7-bromo-3,4-dihydro-benzo[e][1,4]diazepin-5-one (3.1 g, 7.4 mmol) in THF (10 mL) (prepared as described above) was added at −70° C., and subsequently allowed to warm up to at 10° C. over 1 h, then cooled again to −30° C. After 30 min, acetic acid (8 mL) was added at −30° C. and the suspension was allowed to warm up to room temperature and water (8 mL) added and the resulting mixture heated under reflux for 2 h. After cooling, the mixture was evaporated and then dissolved in DCM (30 mL). This solution was then washed with HCl (1 M, 2×15 mL) and sodium hydrogen carbonate (sat., 10 ml), dried (Na2SO4) and evaporated. Chromatography on silica gel eluting with EtOAc. Yield: 0.9 g (24%). m/z 500/502 (M).
Reaction SMILES: [C:1]([O:5][C:6](=[O:29])[NH:7][C:8]1(/[CH:16]=[CH:17]/[C:18]2[CH:23]=[CH:22][C:21]([OH:24])=[C:20]([C:25]([F:28])([F:27])[F:26])[CH:19]=2)[CH2:13][O:12][C:11]([CH3:15])([CH3:14])[O:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[C:1]([O:5][C:6](=[O:29])[NH:7][C:8]1(/[CH:16]=[CH:17]/[C:18]2[CH:23]=[CH:22][C:21]([O:24][CH2:8][CH2:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([CH3:25])[CH:19]=3)=[C:20]([C:25]([F:28])([F:26])[F:27])[CH:19]=2)[CH2:13][O:12][C:11]([CH3:15])([CH3:14])[O:10][CH2:9]1)([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(C)OC(=O)NC1(/C=C/c2ccc(O)c(C(F)(F)F)c2)COC(C)(C)OC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1cccc(CCCOc2ccc(/C=C/C3(NC(=O)OC(C)(C)C)COC(C)(C)OC3)cc2C(F)(F)F)c1
Temperature: 50 °C
Reaction time: 2 h
Yield: 212.7 %

Procedure:
Compound 93-8 (400 mg) was dissolved in N,N-dimethylformamide (10 ml), potassium carbonate (397 mg) and compound 15-2 (246 mg) were added, and the mixture was stirred at 50° C. for 2 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate, washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the object product (560 mg) as a white solid.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]2[N:11]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH:10]([C:19]([OH:21])=[O:20])[CH2:9][S:8]2)[CH:2]=1.[CH3:22]N1CCOCC1.C(OC(Cl)=O)C(C)C.CO>O1CCCC1>[CH3:22][O:20][C:19]([CH:10]1[CH2:9][S:8][CH:7]([C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)[N:11]1[C:12]([O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:13])=[O:21]
Reactant: CC(C)(C)OC(=O)N1C(C(=O)O)CSC1c1cccnc1
Reactant: CN1CCOCC1
Agent: CC(C)COC(=O)Cl
Solvent: C1CCOC1
Solvent: CO
Product: COC(=O)C1CSC(c2cccnc2)N1C(=O)OC(C)(C)C
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 46.7 %

Procedure:
2-(3-pyridinyl)-3-tert-butoxycarbonyl-4-thiazolidinecarboxylic acid (78 g, 251 mmol), prepared as in Example 1, step 2, and 4-methylmorpholine (43 g, 427 mmol) were dissolved in tetrahydrofuran (500 mL ), and cooled in the ice bath. Isobutylchloroformate (38 g, 276 mmol) was added and the yellow suspension was stirred for 0.5 hours. Methanol (250 mL) was added, the cold bath was removed, and the reaction mixture was stirred for 60 hours at ambient temperature. The reaction mixture was concentrated in vacuo and the residue was partitioned between ethyl acetate and saturated aqueous NaHCO3. The aqueous phase was extracted twice with ethyl acetate. The combined organic extracts were washed twice with brine, dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by chromatography on silica gel to give Methyl-2-(3-pyridinyl)-3-tert-butoxycarbonyl-4-thiazolidinecarboxylate (38 g).
Reaction SMILES: [N+:1]([C:4]1[CH:21]=[CH:20][C:7]([CH2:8][N:9]2C(=O)C3C(=CC=CC=3)C2=O)=[CH:6][CH:5]=1)([O-:3])=[O:2].O.NN.C(=O)(O)[O-].[K+]>O1CCCC1>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([CH2:8][NH2:9])=[CH:20][CH:21]=1)([O-:3])=[O:2]
Reactant: O=C1c2ccccc2C(=O)N1Cc1ccc([N+](=O)[O-])cc1
Agent: NN
Agent: O=C([O-])O
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: NCc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Yield: 73 %

Procedure:
To a solution of 2-(4-nitrobenzyl)isoindoline-1,3-dione (1.6 g, 5.33 mmol) in tetrahydrofuran was added hydrazine monohydrate (4 eq). The mixture was refluxed for 6 h. After cooling down to room temperature the mixture was treated with potassium bicarbonate to pH 12˜13, extracted with ethyl acetate and washed with brine. Drying over magnesium sulfate, evaporation of the ethyl acetate and purification by column chromatography gave (4-nitrophenyl)methanamine (592 mg, 65%).
Reaction SMILES: [CH:1]1([N:6]2[CH2:12][C:11]([F:14])([F:13])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26](O)=[O:27])=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:57][CH:58]1[CH2:63][CH2:62][N:61](C(OC(C)(C)C)=O)[CH2:60][CH2:59]1>>[CH:1]1([N:6]2[CH2:12][C:11]([F:13])([F:14])[C:10](=[O:15])[N:9]([CH3:16])[C:8]3[CH:17]=[N:18][C:19]([NH:21][C:22]4[CH:30]=[CH:29][C:25]([C:26]([NH:57][CH:58]5[CH2:63][CH2:62][NH:61][CH2:60][CH2:59]5)=[O:27])=[CH:24][C:23]=4[O:31][CH3:32])=[N:20][C:7]2=3)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CC(C)(C)OC(=O)N1CCC(N)CC1
Reactant: COc1cc(C(=O)O)ccc1Nc1ncc2c(n1)N(C1CCCC1)CC(F)(F)C(=O)N2C
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Product: COc1cc(C(=O)NC2CCNCC2)ccc1Nc1ncc2c(n1)N(C1CCCC1)CC(F)(F)C(=O)N2C

Procedure:
The title compound was synthesized from 4-(9-Cyclopentyl-7,7-difluoro-5-methyl-6-oxo-6,7,8,9-tetrahydro-5H-pyrimido[5,4-b][1,4]diazepin-2-ylamino)-3-methoxybenzoic acid as described in the General procedure for amide bond synthesis using HATU and tert-butyl 4-aminopiperidine-1-carboxylate, where Boc was removed using TFA in DCM. The final compound was purified by reverse phase HPLC and basified to give the free base. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.43 (qd, J=11.9, 3.8 Hz, 2H) 1.54-1.66 (m, 5H) 1.66-1.77 (m, 4H) 1.98 (br. s, 2H) 2.52 (d, J=1.8 Hz, 2H) 2.98 (d, J=11.9 Hz, 2H) 3.79-3.87 (m, 1H) 3.93 (s, 3H) 4.04 (t, J=14.2 Hz, 2H) 4.76 (quin, J=8.1 Hz, 1H) 7.48 (d, 1H) 7.50 (s, 1H) 7.96 (s, 1H) 8.13 (d, J=8.1 Hz, 1H) 8.26 (d, J=8.1 Hz, 1H) 8.26 (s, 1H). [M+H] calc'd for C26H33F2N7O3, 530. found 530.
Reaction SMILES: [CH3:1][S:2]([CH3:5])(=[O:4])=[O:3].[Li]CCCC.CN(P(N(C)C)(N(C)C)=O)C.[Br:22][C:23]1[CH:28]=[CH:27][C:26]([NH:29][C:30]2[C:31]([CH:40]=[O:41])=[CH:32][C:33]3[NH:37][CH:36]=[N:35][C:34]=3[C:38]=2[F:39])=[C:25]([Cl:42])[CH:24]=1>C1COCC1>[Br:22][C:23]1[CH:28]=[CH:27][C:26]([NH:29][C:30]2[C:31]([C:40](=[O:41])[CH2:1][S:2]([CH3:5])(=[O:4])=[O:3])=[CH:32][C:33]3[NH:37][CH:36]=[N:35][C:34]=3[C:38]=2[F:39])=[C:25]([Cl:42])[CH:24]=1
Reactant: CS(C)(=O)=O
Reactant: O=Cc1cc2[nH]cnc2c(F)c1Nc1ccc(Br)cc1Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Product: CS(=O)(=O)CC(=O)c1cc2[nH]cnc2c(F)c1Nc1ccc(Br)cc1Cl
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 97.5 %

Procedure:
To a solution of methyl sulfone (65 mg, 0.68 mmol) in THF (1.5 mL) is added a solution of n-BuLi (0.27 mL, 0.68 mmol, 2.5 M solution in hexane) at −78° C. After stirring for 5 minutes, HMPA (0.1 mL) is added. After stirring for additional 10 minutes, a solution of 6-(4-bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carbaldehyde 10f (26 mg, 0.069 mmol) in THF (1 mL) is added. The resulting solution is stirred for 1.5 hours at −78° C. The reaction is quenched with saturated aqueous NH4Cl, warmed to room temperature, and diluted with EtOAc. The organic layer is washed with water, dried over MgSO4, filtered, concentrated in vacuo, and purified by flash chromatography (3% MeOH in CH2Cl2) to give the crude desired product (31 mg, 96%) which is used directly without further purification: MS APCI (+) m/z 462, 464 (M+, Br pattern) detected.
Reaction SMILES: [CH2:1]([O:3][C:4]([C@@H:6]([NH:15][C@H:16]([C:18](Cl)=[O:19])[CH3:17])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:5])[CH3:2].[CH2:21]([OH:23])[CH3:22]>>[CH2:21]([O:23][C:18](=[O:19])[C@H:16]([CH3:17])[NH:15][C@H:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH3:22]
Reactant: CCO
Reactant: CCOC(=O)[C@H](CCc1ccccc1)N[C@@H](C)C(=O)Cl
Product: CCOC(=O)[C@H](C)N[C@@H](CCc1ccccc1)C(=O)OCC

Procedure:
In the Examples, the purity of the obtained inorganic acid salt of N-[1(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanylchloride was measured by reacting the obtained acid chloride with ethanol in the presence of a base to produce N-[1(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanine ethylester, which was then subjected to a high performance liquid chromatography (hereinafter referred to as "HPLC"). More particularly, about 100 mg of the sample of the acid chloride was put in a 10 ml messflask, to which absolute ethanol containing 0.3% (w/v) of triethylamine was added to give 10 ml of the solution and the esterification was carried out by stirring the solution with a magnetic stirrer at room temperature for 30 minutes. To 1.0 ml of the sample of the thus obtained solution, 4 ml of ethanol solution containing 10 mg of n-propylbenzoic acid (internal standard reagent) was added, the mixture was subjected to the analysis by the column chromatography under the following conditions.
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].C[O:8][C:9]([CH:11]1[CH2:20][CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[NH:12]1)=O.[OH-].[Na+].O>C1COCC1.C(OCC)C>[OH:8][CH2:9][CH:11]1[CH2:20][CH2:19][C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[NH:12]1
Reactant: COC(=O)C1CCc2ccccc2N1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: CCOCC
Solvent: C1CCOC1
Product: OCC1CCc2ccccc2N1
Temperature: 25 °C
Reaction time: 3 h
Yield: 106.9 %

Procedure:
To a suspension of LiAlH4 (8.3 g, 0.22 mol) in THF (200 mL) was added dropwise 2-methoxycarbonyltetrahydroquinoline (42 g, 0.22 mol) in THF (200 mL) at 0° C. The mixture was stirred for 3 h at room temperature and refluxed for 0.5 h. The excess reagent was decomposed by addition of aqueous sodium hydroxide in THF. To the mixture was added 1N aqueous NaOH, water, and diethyl ether, successively. The organic layer was separated, washed with brine, dried over magnesium sulfate, and concentrated to give 38.4 g of 2-hydroxymethyltetrahydroquinoline (quant).
Reaction SMILES: [Cl:1][C:2]1[CH:14]=[C:13]2[C:5]([CH:6]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=3)[C:7]3[CH:12]=[N:11][CH:10]=[N:9][C:8]=32)=[CH:4][CH:3]=1.[Mn]([O-])(=O)(=O)=[O:23].[K+]>CC(C)=O>[Cl:1][C:2]1[CH:14]=[C:13]2[C:5]([C:6]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=3)([OH:23])[C:7]3[CH:12]=[N:11][CH:10]=[N:9][C:8]=32)=[CH:4][CH:3]=1
Reactant: Clc1ccc(C2c3ccc(Cl)cc3-c3ncncc32)cc1
Reactant: O=[Mn](=O)(=O)[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: OC1(c2ccc(Cl)cc2)c2ccc(Cl)cc2-c2ncncc21
Temperature: 25 °C
Reaction time: 8 h
Yield: 26.5 %

Procedure:
To a stirred solution of 11.0 g of 8-chloro-5-(4-chlorophenyl)-5H-indeno[1,2-d]pyrimidine in 300 ml of acetone were added 6.32 g of potassium permanganate. The mixture was stirred under a nitrogen atmosphere for 2 hours at which time an additional 6.32 g of potassium permanganate were added. The mixture was stirred overnight at room temperature, filtered, and the filtrate concentrated in vacuo. The residue was taken up in a mixture of ethyl acetate and a saturated sodium chloride solution. The layers were separated and the organic layer was washed with water, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was crystallized first from ethyl acetate/isooctane and then from ethyl acetate to provide 3.06 g of the desired title product, m.p. 194°-195.5° C.
Reaction SMILES: C[O:2][C:3]1[CH:4]=[C:5]([CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[CH:6]=[CH:7][CH:8]=1.B(Br)(Br)Br.O>C(Cl)Cl>[CH2:9]([C:5]1[CH:4]=[C:3]([OH:2])[CH:8]=[CH:7][CH:6]=1)[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]
Reactant: CCCCCCCCCCCCCCc1cccc(OC)c1
Agent: BrB(Br)Br
Solvent: O
Solvent: ClCCl
Product: CCCCCCCCCCCCCCc1cccc(O)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 136.8 g of 3-methoxy-1-tetradecylbenzene in 600 ml of methylene chloride, cooled to -78° C., under inert gas, was added dropwise a solution of 112.8 g of boron tribromide in 100 ml of methylene chloride. The mixture was kept at -78° C. for 1 hour then allowed to warm slowly to room temperature followed by stirring for 16 hours. The mixture was cooled to 0° C. and cold water added dropwise. The organic layer was separated and washed with aqueous sodium bicarbonate, dried and the solvent evaporated. The residue was poured onto crushed ice and 107 g of the desired product collected as a white solid, m.p. 38°-40° C.
Reaction SMILES: C([O:5][C:6]([C:8]1[N:13]2[C:14](=[O:28])[CH:15]([NH:16][C:17](=[O:27])[CH2:18][S:19]([CH2:22][C:23]([F:26])([F:25])[F:24])(=[O:21])=[O:20])[C@H:12]2[S:11][CH2:10][C:9]=1[CH:29]([S:35][C:36]1[NH:40][N:39]=[N:38][N:37]=1)[CH2:30][CH2:31][C:32](=[O:34])[NH2:33])=[O:7])(C)(C)C.FC(F)(F)C(O)=O>C(#N)C>[F:25][C:23]([F:24])([F:26])[CH2:22][S:19]([CH2:18][C:17]([NH:16][CH:15]1[C:14](=[O:28])[N:13]2[C:8]([C:6]([OH:7])=[O:5])=[C:9]([CH:29]([S:35][C:36]3[NH:40][N:39]=[N:38][N:37]=3)[CH2:30][CH2:31][C:32](=[O:34])[NH2:33])[CH2:10][S:11][C@H:12]12)=[O:27])(=[O:20])=[O:21]
Reactant: CC(C)(C)OC(=O)C1=C(C(CCC(N)=O)Sc2nnn[nH]2)CS[C@@H]2C(NC(=O)CS(=O)(=O)CC(F)(F)F)C(=O)N12
Solvent: CC#N
Solvent: O=C(O)C(F)(F)F
Product: NC(=O)CCC(Sc1nnn[nH]1)C1=C(C(=O)O)N2C(=O)C(NC(=O)CS(=O)(=O)CC(F)(F)F)[C@H]2SC1
Reaction time: 3 h

Procedure:
The ester is dissolved in acetonitrile and trifluoroacetic acid is added. The solution is stirred for three hours, then evaporated to dryness to give the title compound.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11](=O)/[C:10](=[CH:13]/[N:14](C)C)/[CH2:9][CH2:8][O:7][C:6]=2[CH:17]=1.Cl.Cl.[NH2:20]N>C(O)(C)C.O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11]3[C:10]([CH2:9][CH2:8][O:7][C:6]=2[CH:17]=1)=[CH:13][NH:14][N:20]=3
Reactant: CN(C)/C=C1\CCOc2cc(Br)ccc2C1=O
Reactant: NN
Agent: Cl
Solvent: O
Solvent: CC(C)O
Product: Brc1ccc2c(c1)OCCc1c[nH]nc1-2
Temperature: 100 °C
Reaction time: 2 h
Yield: 90.2 %

Procedure:
To a suspension of 8-bromo-4-[1-dimethylamino-meth-(E)-ylidene]-3,4-dihydro-2H-benzo[b]-oxepin-5-one (5.32 g, 17.9 mmol) in isopropyl alcohol (50 mL) was added powdered hydrazine dihydrochloride (3.77 g, 35.9 mmol) at room temperature, then the mixture stirred for 2 h. The reaction mixture was diluted with water (20 mL) and then heated at 100° C. for 2 h before cooling to room temperature. The reaction mixture was concentrated in vacuo to remove the volatile solvent. The resulting suspension was filtered and the filtrate washed with water and dried under vacuum at 40° C. to yield 8-Bromo-4,5-dihydro-2H-6-oxa-1,2-diaza-benzo[e]azulene as a pale yellow solid (4.28 g, 90%). 1H NMR δ (ppm) (DMSO-d): 8.07 (1H, d, J=8.52 Hz), 7.64 (1H, s), 7.30-7.24 (1H, m), 7.21 (1H, d, J=2.07 Hz), 4.24 (2H, dd, J=5.63, 4.50 Hz), 3.00 (2H, t, J=5.09 Hz).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([SH:10])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].[Hg](C#N)C#N.[C:16]([O:19][C@@H:20]1[C@@H:25]([O:26][C:27](=[O:29])[CH3:28])[C@H:24]([O:30][C:31](=[O:33])[CH3:32])[CH2:23][S:22][C@@H:21]1Br)(=[O:18])[CH3:17]>>[C:16]([O:19][C@@H:20]1[C@@H:25]([O:26][C:27](=[O:29])[CH3:28])[C@H:24]([O:30][C:31](=[O:33])[CH3:32])[CH2:23][S:22][C@H:21]1[S:10][C:6]1[CH:7]=[CH:8][CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=1)(=[O:18])[CH3:17]
Reactant: O=[N+]([O-])c1cccc(S)c1
Reactant: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@@H](Br)SC[C@H]1OC(C)=O
Agent: N#C[Hg]C#N
Product: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](Sc2cccc([N+](=O)[O-])c2)SC[C@H]1OC(C)=O
Yield: 26.9 %

Procedure:
If the procedure described in Preparation I is followed starting from 10 g (64.5.10-3 mol) of 3-nitrobenzenethiol, 16.29 g (64.5.10-3 mol) of mercuric cyanide (Hg(CN)2) and 25.2 g (70.9.10-3 mol) of 2,3,4-tri-O-acetyl-5-thio-α-D-xylopyranosyl bromide, 7.44 g (yield: 27%) of the expected product are obtained after purification by flash chromatography using a toluene/ethyl acetate mixture (9/1 v/v) as the eluent, followed by crystallization from ether.
Reaction SMILES: [CH3:1][C:2]1([CH3:36])[C:7]2[S:8][CH2:9][CH2:10][C:6]=2[C:5]2[C:11]([OH:35])=[CH:12][C:13]([CH:15]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[CH3:16])=[CH:14][C:4]=2[O:3]1.C(O)(=O)C.[S:41]1[CH2:46][CH2:45][N:44]([CH2:47][CH2:48][CH2:49][C:50](O)=[O:51])[CH2:43][CH2:42]1.C1(N=C=NC2CCCCC2)CCCCC1>>[CH3:36][C:2]1([CH3:1])[C:7]2[S:8][CH2:9][CH2:10][C:6]=2[C:5]2[C:11]([O:35][C:50](=[O:51])[CH2:49][CH2:48][CH2:47][N:44]3[CH2:43][CH2:42][S:41][CH2:46][CH2:45]3)=[CH:12][C:13]([CH:15]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[CH3:16])=[CH:14][C:4]=2[O:3]1
Reactant: CCCCCCCCCCCCCCCCCCC(C)c1cc(O)c2c(c1)OC(C)(C)C1=C2CCS1
Reactant: O=C(O)CCCN1CCSCC1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: CC(=O)O
Product: CCCCCCCCCCCCCCCCCCC(C)c1cc(OC(=O)CCCN2CCSCC2)c2c(c1)OC(C)(C)C1=C2CCS1

Procedure:
1,2-Dihydro-7-(2-eicosyl)-9-hydroxy-4-oxo-4H-thieno[2,3-c] [1]benzopyran is reacted with methyl magnesium bromide according to the procedure described hereinabove in Example 8 to give 1,2-dihydro-4,4-dimethyl-7-(2-eicosyl)-9-hydroxy-4H-thieno[2,3-c] [1]benzopyran. The benzopyran is then reacted with γ-thiomorpholinobutyric acid, acetate salt and dicyclohexylcarbodiimide according to the method of Example 10 to yield the desired ester.
Reaction SMILES: O1CCCC1.[ClH:6].[CH2:7]([N:9]1[CH:14]([CH2:15][O:16][CH2:17][CH:18]([CH3:20])[CH3:19])[CH2:13][N:12]([C:21]2[CH:26]=[CH:25][C:24]([NH:27][S:28]([CH3:31])(=[O:30])=[O:29])=[CH:23][CH:22]=2)[C:11](=O)[CH2:10]1)[CH3:8].[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+]>CCOC(C)=O.O>[ClH:6].[ClH:6].[CH2:7]([N:9]1[CH2:10][CH2:11][N:12]([C:21]2[CH:22]=[CH:23][C:24]([NH:27][S:28]([CH3:31])(=[O:30])=[O:29])=[CH:25][CH:26]=2)[CH2:13][CH:14]1[CH2:15][O:16][CH2:17][CH:18]([CH3:19])[CH3:20])[CH3:8]
Reactant: CCN1CC(=O)N(c2ccc(NS(C)(=O)=O)cc2)CC1COCC(C)C
Agent: Cl
Agent: [Al+3]
Agent: [H-]
Solvent: O
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CCN1CCN(c2ccc(NS(C)(=O)=O)cc2)CC1COCC(C)C
Temperature: 25 °C

Procedure:
To 5 mL of tetrahydrofuran under a nitrogen atmosphere add 2.6 g (6.8 mmol) of N-[4-[4-ethyl-5-[(2-methylpropoxy)methyl]-2-oxopiperazin-1-yl]phenyl]methanesulfonamide hydrochloride and 0.51 (13 mmol) of lithium aluminum hydride. When the additions are complete stir the reaction at reflux. Monitor the progress of the reaction by thin-layer chromatography on silica gel (CH2Cl2 :MeOH, 9:1). Upon completion of the reaction cool to room temperature and add 0.5 mL of H2O, 0.5 mL of 2N NaOH, 1.5 mL of H2O, and 50 mL of EtOAc. Remove the precipitate by suction filtration through celite and remove the solvent in vacuo. Chromatograph the residue on silica gel with CH2Cl2 :MeOH. Combine the product fractions and remove the solvent in vacuo. Dissolve the residue in methanolic HCl and remove the solvent in vacuo. Recrystallize the material from isopropanol to afford the title compound.
Reaction SMILES: [NH2:1][CH:2]1[C:23](=[O:24])[N:4]2[C:5]([C:10]([O:12]CC3C=CC([N+]([O-])=O)=CC=3)=[O:11])=[C:6]([Cl:9])[CH2:7][S:8][C@H:3]12.[Sn].Cl>CO.O>[NH2:1][CH:2]1[C:23](=[O:24])[N:4]2[C:5]([C:10]([OH:12])=[O:11])=[C:6]([Cl:9])[CH2:7][S:8][C@H:3]12
Reactant: NC1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(Cl)CS[C@H]12
Agent: Cl
Agent: [Sn]
Solvent: CO
Solvent: O
Product: NC1C(=O)N2C(C(=O)O)=C(Cl)CS[C@H]12
Reaction time: 1 h

Procedure:
p-Nitrobenzyl 7-amino-3-chloro-3-cephem-4-carboxylate (10 gm) was suspended in a mixture of methanol (120 ml) and water (25 ml). Tin powder was charged at 30° C., followed by the addition of concentrated HCl (25 ml) in a methanol (20 ml) and water (5 ml) mixture over a period of 15 minutes. The reaction mixture was stirred for 1 hour. After completion of the reaction, aq. KHCO3 was added to bring the pH to 8.0, followed by the addition of activated carbon. After stirring for 10 minutes, the mixture was filtered. To the filtrate was added aq. HCl to bring the pH to 4.0. The product thus separated was filtered and dried. Yield: 3.9 g (68%).
Reaction SMILES: [NH2:1][C:2]1[C:7]([NH2:8])=[CH:6][C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1.[CH:12](=O)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>[N+](C1C=CC=CC=1)([O-])=O>[N+:9]([C:5]1[CH:6]=[C:7]2[N:8]=[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[NH:1][C:2]2=[N:3][CH:4]=1)([O-:11])=[O:10]
Reactant: O=Cc1ccccc1
Reactant: Nc1cc([N+](=O)[O-])cnc1N
Solvent: O=[N+]([O-])c1ccccc1
Product: O=[N+]([O-])c1cnc2[nH]c(-c3ccccc3)nc2c1

Procedure:
14.05 g 2,3-diamino-5-nitropyridine and 9.68 g benzaldehyde in 250 ml nitrobenzene were heated to 140-150° C. for 15 hrs. The solvent is removed by vacuum distillation and the residue is dispersed in ethyl acetate, filtered, and the filter residue washed thoroughly with ethyl acetate.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=3)=[N:8][C:7]=2[CH:18]=1.C[O:20][C:21](=[O:34])[CH2:22][O:23][C:24]1[CH:32]=[CH:31][C:30]([SH:33])=[C:29]2[C:25]=1[CH2:26][CH2:27][CH2:28]2>>[F:17][C:13]1[CH:12]=[C:11]([C:9]2[O:10][C:6]3[CH:5]=[CH:4][C:3]([CH2:2][S:33][C:30]4[CH:31]=[CH:32][C:24]([O:23][CH2:22][C:21]([OH:34])=[O:20])=[C:25]5[C:29]=4[CH2:28][CH2:27][CH2:26]5)=[CH:18][C:7]=3[N:8]=2)[CH:16]=[CH:15][CH:14]=1
Reactant: Fc1cccc(-c2nc3cc(CCl)ccc3o2)c1
Reactant: COC(=O)COc1ccc(S)c2c1CCC2
Product: O=C(O)COc1ccc(SCc2ccc3oc(-c4cccc(F)c4)nc3c2)c2c1CCC2

Procedure:
Compound 69C and Compound 1D were reacted in a manner analogous to Compound 59A to give the title product. MS m/z 464 (M+1).