Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][CH:2]([CH2:20][CH:21]([CH3:23])[CH3:22])[CH:3]([NH:7][CH:8]([C:10]([N:12]1[CH2:19][CH2:18][CH2:17][C@H:13]1[C:14]([OH:16])=[O:15])=[O:11])[CH3:9])[C:4]([OH:6])=[O:5].[C:24](Cl)(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>>[C:24]([NH:1][CH:2]([CH2:20][CH:21]([CH3:23])[CH3:22])[CH:3]([NH:7][CH:8]([C:10]([N:12]1[CH2:19][CH2:18][CH2:17][C@H:13]1[C:14]([OH:16])=[O:15])=[O:11])[CH3:9])[C:4]([OH:6])=[O:5])(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: CC(C)CC(N)C(NC(C)C(=O)N1CCC[C@H]1C(=O)O)C(=O)O
Reactant: O=C(Cl)c1ccccc1
Product: CC(C)CC(NC(=O)c1ccccc1)C(NC(C)C(=O)N1CCC[C@H]1C(=O)O)C(=O)O

Procedure:
A solution of N-(2-amino-1-carboxy-4-methylpentyl)-D,L-alanyl-L-proline (prepared as described in Example 78) in aqueous alkali is treated with benzoyl chloride to yield N-(2-benzamido-1-carboxy-4-methylpentyl)-D,L-alanyl-L-proline. The mass spectrum of disilylated material had peaks at 562 (M+ -15), 460,389 (base peak), 364,242 and 174 m/e.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:12]2[O:13][CH:14]=[CH:15][CH:16]=2)=[N:4][C:5]([NH2:11])=[N:6][C:7]=1S(C)=O.[C:17]1([CH2:23][CH2:24][CH2:25][NH2:26])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>O1CCOCC1>[Cl:1][C:2]1[C:7]([NH:26][CH2:25][CH2:24][CH2:23][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[N:6][C:5]([NH2:11])=[N:4][C:3]=1[C:12]1[O:13][CH:14]=[CH:15][CH:16]=1
Reactant: CS(=O)c1nc(N)nc(-c2ccco2)c1Cl
Reactant: NCCCc1ccccc1
Solvent: C1COCCO1
Product: Nc1nc(NCCCc2ccccc2)c(Cl)c(-c2ccco2)n1

Procedure:
From 5-chloro-4-furan-2-yl-6-methanesulfinyl-pyrimidin-2-yl-amine and 3-phenylpropylamine in dioxane. ES-MS m/e (%): 331 (M{37C }+H+, 30), 329 (M{35Cl}+H+, 100).
Reaction SMILES: [Cl:1][C:2]1[CH:16]=[CH:15][CH:14]=[CH:13][C:3]=1[CH:4](O)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[Cl:11].[C:17]([O:21][CH3:22])(=[O:20])[CH2:18][SH:19]>>[Cl:1][C:2]1[CH:16]=[CH:15][CH:14]=[CH:13][C:3]=1[CH:4]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[Cl:11])[S:19][CH2:18][C:17]([O:21][CH3:22])=[O:20]
Reactant: COC(=O)CS
Reactant: OC(c1ccccc1Cl)c1ccccc1Cl
Product: COC(=O)CSC(c1ccccc1Cl)c1ccccc1Cl
Yield: 23 %

Procedure:
Following the procedure of Example 4, 2,2'-dichlorobenzhydrol, synthesized in accordance with C. W. N. Cumper, et. al. in J. C. S. Perkins Trans. II (1), 106 (1972)] is reacted with methyl thioglycolate for 4 hours at 50°-60° C. Chromatography on silica gel, eluting with a gradient of 5% ethyl acetate in hexane to 10% ethyl acetate in hexane, gives methyl [[bis-(2-chlorophenyl)methyl]thio]acetate as a white solid in 23% yield: melting point 90°-92° C.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=2[O:11][CH2:12][C:13]#[N:14])[C:5]([Cl:19])=[CH:4][N:3]=1.[NH2:20][C:21]1[CH:34]=[CH:33][C:24]2[CH2:25][CH2:26][CH2:27][C:28](=[O:32])[N:29]([CH2:30][CH3:31])[C:23]=2[CH:22]=1>>[Cl:19][C:5]1[C:6]([NH:8][C:9]2[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=2[O:11][CH2:12][C:13]#[N:14])=[N:7][C:2]([NH:20][C:21]2[CH:34]=[CH:33][C:24]3[CH2:25][CH2:26][CH2:27][C:28](=[O:32])[N:29]([CH2:30][CH3:31])[C:23]=3[CH:22]=2)=[N:3][CH:4]=1
Reactant: N#CCOc1ccccc1Nc1nc(Cl)ncc1Cl
Reactant: CCN1C(=O)CCCc2ccc(N)cc21
Product: CCN1C(=O)CCCc2ccc(Nc3ncc(Cl)c(Nc4ccccc4OCC#N)n3)cc21

Procedure:
{2-[5-Chloro-2-(1-ethyl-2-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-8-ylamino)-pyrimidin-4-ylamino]-phenoxy}-acetonitrile was prepared from [2-(2,5-Dichloro-pyrimidin-4-ylamino)-phenoxy]-acetonitrile and 8-Amino-1-ethyl-1,3,4,5-tetrahydro-1-benzazepin-2-one in an analogous manner to. Example 12211d. (120° C., 20 min). Title compound was isolated as a white foam: 67 mg (61%) after silica gel chromatography (ISCO 12 g, 0-100% EtOAc in hexanes). HPLC purity 88%, LCMS 463.24 (M+H), 1H-NMR (CDCl3, 400 MHz) δ: 8.35 (d, J=8.0 Hz, 1H), 8.12 (s, 1H), 7.60 (s, 2H), 7.35 (s, 1H), 7.23 (d, J=6.5 Hz, 1H), 7.21-7.05 (m, 4H), 4.90 (s, 2H), 3.90-3.50 (bm, 2H), 2.71-2.60 (m, 2H), 2.34-2.23 (m, 2H), 2.05-2.12 (m, 2H), 1.08 (t, J=7.1 Hz, 3H).
Reaction SMILES: C(O[C:4]1[C:13]2[CH:12]=[CH:11][CH:10]=[C:9]3[NH:14][CH:15]=[C:7]([C:8]=23)[CH2:6][N:5]=1)C.[CH3:16][N:17]([CH3:22])[CH2:18][CH2:19][CH2:20][NH2:21].Cl>C(O)C>[CH3:16][N:17]([CH3:22])[CH2:18][CH2:19][CH2:20][NH:21][C:4]1[C:13]2[CH:12]=[CH:11][CH:10]=[C:9]3[NH:14][CH:15]=[C:7]([C:8]=23)[CH2:6][N:5]=1
Reactant: CCOC1=NCc2c[nH]c3cccc1c23
Reactant: CN(C)CCCN
Agent: Cl
Solvent: CCO
Product: CN(C)CCCNC1=NCc2c[nH]c3cccc1c23

Procedure:
A mixture of 5-ethoxy-1,3-dihydropyrrolo[4,3,2-de]isoquinoline (5 g, 25 mmoles), described in Example 5, ethanol (50 ml), 3-(dimethylamino)propylamine (2.7 g, 26.4 mmoles) and conc. HCl (12.5 ml, 29 mmoles) in 50 ml of ethanol is heated at reflux for 7 hours. Some ethanol is removed by distillation, then ether and saturated HCl in ethanol (2 ml) is added. The precipitate is collected. Recrystallization for ethanol-ethyl acetate (a small amount of HCl in ethanol being added) gives the hydrochloride salt of the title compound, mp 289° - 290°C.
Reaction SMILES: C(OC([NH:8][CH2:9][CH:10]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][NH:19][C:20]([C:22]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[N:24]([CH3:31])[CH:23]=2)=[O:21])[CH2:11]1)=O)(C)(C)C.[NH2:32][C:33]1[C:41]([Cl:42])=[CH:40][C:36]([C:37]([OH:39])=O)=[C:35]([O:43][CH3:44])[CH:34]=1>>[NH2:32][C:33]1[C:41]([Cl:42])=[CH:40][C:36]([C:37]([NH:8][CH2:9][CH:10]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][NH:19][C:20]([C:22]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[N:24]([CH3:31])[CH:23]=3)=[O:21])[CH2:11]2)=[O:39])=[C:35]([O:43][CH3:44])[CH:34]=1
Reactant: Cn1cc(C(=O)NCCCCN2CCC(CNC(=O)OC(C)(C)C)C2)c2ccccc21
Reactant: COc1cc(N)c(Cl)cc1C(=O)O
Product: COc1cc(N)c(Cl)cc1C(=O)NCC1CCN(CCCCNC(=O)c2cn(C)c3ccccc23)C1

Procedure:
N-(4-(3-tert-Butoxycarbonylaminomethylpyrrolidin-1-yl)butyl)-1-methyl-1 H-indole-3-carboxamide (0.67 g) as starting compound was reacted and treated in the same manner as in Example 67 using 4-amino-5-chloro-2-methoxybenzoic acid (0.42 g) to give N-(4-(3-(4-amino-5-chloro-2-methoxybenzoylaminomethyl)pyrrolidin-1-yl)butyl)-1-methyl-1 H-indole-3-carboxamide.
Reaction SMILES: O=P(Cl)(Cl)[Cl:3].[CH2:6]([C:8]1[C:13]([I:14])=[C:12](O)[CH:11]=[CH:10][N:9]=1)[CH3:7].CCN(CC)CC>CC#N>[Cl:3][C:12]1[CH:11]=[CH:10][N:9]=[C:8]([CH2:6][CH3:7])[C:13]=1[I:14]
Reactant: CCc1nccc(O)c1I
Reactant: O=P(Cl)(Cl)Cl
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CCc1nccc(Cl)c1I
Temperature: 60 °C

Procedure:
A solution of 165.1 g (1.08 mol) POCl3 in 100 mL CH3CN is added dropwise to a solution of 27.1 g (108 mmol) 2-ethyl-3-iodo-pyridin-4-ol in 150 mL CH3CN at RT. Then Et3N (21.9 g, 216 mmol) is added slowly over 20 min before the reaction mixture is heated to 60° C. for 3 h. The reaction mixture is evaporated in vaccuo to afford an oil. This crude oil is poured into the crushed ice, and the aqueous phase is extracted with petroleum ether/EtOAc (3×, 200 mL; 10:1). The organic phase is collected, dried over anhydrous Na2SO4. The solvent is removed in vacuo to afford desired product. Yield: 22.0 g (76%).
Reaction SMILES: [CH3:1][CH:2]([CH3:7])[CH2:3][CH2:4][CH2:5][OH:6].[CH3:8][S:9](Cl)(=[O:11])=[O:10]>>[CH3:8][S:9]([O:6][CH2:5][CH2:4][CH2:3][CH:2]([CH3:7])[CH3:1])(=[O:11])=[O:10]
Reactant: CC(C)CCCO
Reactant: CS(=O)(=O)Cl
Product: CC(C)CCCOS(C)(=O)=O

Procedure:
The title compound was prepared by following the general procedure of Example 43 for mesylation as a colorless oil (620 mg, 63%) from 4-methyl-1-pentanol (511 mg, 5.00 mmol) and methanesulfonyl chloride (844 mg, 7.50 mmol). 1H NMR (CDCl3, 300 MHz) δ0.88 (d, 6H, J=4.7 Hz), 1.23-1.31 (m, 2H), 1.53-1.62 (m, 1H), 1.70-1.80 (m, 2H), 3.00 (s, 3H), 4.21 (t, 2H, J=6.6 Hz) ppm.
Reaction SMILES: [NH2:1][C:2]1[C:23]([Cl:24])=[CH:22][C:5]([C:6]([NH:8][CH2:9][CH:10]2[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][NH2:21])[CH2:12][CH2:11]2)=[O:7])=[C:4]([O:25][CH3:26])[CH:3]=1.[S:27]1[CH:31]=[CH:30][CH:29]=[C:28]1[CH:32]=O>>[NH2:1][C:2]1[C:23]([Cl:24])=[CH:22][C:5]([C:6]([NH:8][CH2:9][CH:10]2[CH2:11][CH2:12][N:13]([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][NH:21][CH2:32][C:28]3[S:27][CH:31]=[CH:30][CH:29]=3)[CH2:14][CH2:15]2)=[O:7])=[C:4]([O:25][CH3:26])[CH:3]=1
Reactant: O=Cc1cccs1
Reactant: COc1cc(N)c(Cl)cc1C(=O)NCC1CCN(CCCCCN)CC1
Product: COc1cc(N)c(Cl)cc1C(=O)NCC1CCN(CCCCCNCc2cccs2)CC1
Yield: 99.9 %

Procedure:
4-Amino-N-(1-(5-aminopentyl)piperidin-4-ylmethyl)-5-chloro-2-methoxybenzamide (2 g) as starting compound and 2-thiophenecarboxaldehyde (0.64 g) were reacted and treated in the same manner as in Example 121 to give 2.5 g of 4-amino-5-chloro-2-methoxy-N-((1-(5-(2-thienylmethylamino)pentyl)piperidin-4-yl)methyl)benzamide.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7](=O)[CH2:8][CH2:9][C:10](=O)[CH3:11])[CH:2]=1>C(OCC)(=O)C>[CH3:7][C:3]1[CH:4]=[CH:5][C:7]([C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)=[C:8]2[C:2]=1[CH:11]=[CH:10][CH2:9]2
Reactant: CC(=O)CCC(=O)c1cccnc1
Solvent: CCOC(C)=O
Product: Cc1ccc(-c2cccnc2)c2c1C=CC2
Yield: 48 %

Procedure:
17.7 g (100 mmol}of 1-(3-pyridyl)-1,4-pentanedione were reacted analogously to Example 6. Column chromatography with ethyl acetate as the mobile phase gave 9.98 g (48 %) of the indene 12.
Reaction SMILES: [NH:1](C(OC(C)(C)C)=O)[C@H:2]([C:11]([NH:13][C@@H:14]([C:20]([NH:22][CH2:23][C:24]([N:26]([CH2:44][CH3:45])[C@H:27]([C:35]([NH:37][NH:38][C:39]([CH2:41][CH2:42][CH3:43])=[O:40])=[O:36])[CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:25])=[O:21])[CH2:15][CH2:16][S:17]([CH3:19])=[O:18])=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.C(O)(=O)CS.N[C@H](C(O)=O)CCSC.N[C@H](C(O)=O)CC1C=CC(O)=CC=1>CO>[NH2:1][C@H:2]([C:11]([NH:13][C@@H:14]([C:20]([NH:22][CH2:23][C:24]([N:26]([CH2:44][CH3:45])[C@H:27]([C:35]([NH:37][NH:38][C:39]([CH2:41][CH2:42][CH3:43])=[O:40])=[O:36])[CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:25])=[O:21])[CH2:15][CH2:16][S:17]([CH3:19])=[O:18])=[O:12])[CH2:3][C:4]1[CH:5]=[CH:6][C:7]([OH:10])=[CH:8][CH:9]=1
Reactant: CCCC(=O)NNC(=O)[C@H](Cc1ccccc1)N(CC)C(=O)CNC(=O)[C@@H](CCS(C)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)OC(C)(C)C
Agent: CSCC[C@H](N)C(=O)O
Agent: N[C@@H](Cc1ccc(O)cc1)C(=O)O
Agent: O=C(O)CS
Solvent: CO
Product: CCCC(=O)NNC(=O)[C@H](Cc1ccccc1)N(CC)C(=O)CNC(=O)[C@@H](CCS(C)=O)NC(=O)[C@@H](N)Cc1ccc(O)cc1

Procedure:
By the same procedure as in Example 2-(IV), there was obtained the objective compound from 0.50 g of BOC-Tyr-(D)-Met(O)-Gly-EtPhe-NHNHCOCH2CH2CH3. Yield: 0.29 g, [α]D24 +17.6° (c=0.52, MeOH), Rf2 0.26. Amino acid analysis (4% thioglycolic acid/6 N hydrochloric acid hydrolysis): Gly 1.00(1), Met 1.03(1), Tyr 0.98(1).
Reaction SMILES: [Cl:1][C:2]1[C:3](F)=[N:4][CH:5]=[CH:6][CH:7]=1.[F:9][C:10]1([F:21])[CH2:13][CH:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:11]1.C[Si](C)(C)[N-][Si](C)(C)C.[Na+]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:3]([C:12]2([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:11][C:10]([F:21])([F:9])[CH2:13]2)=[N:4][CH:5]=[CH:6][CH:7]=1
Reactant: Fc1ncccc1Cl
Reactant: CC(C)(C)OC(=O)C1CC(F)(F)C1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)C1(c2ncccc2Cl)CC(F)(F)C1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 43.8 %

Procedure:
A solution of 3-chloro-2-fluoropyridine (500 mg, 3.8 mmol) and tert-butyl 3,3-difluorocyclobutanecarboxylate (Preparation 227, 877 mg, 4.6 mmol) in toluene (13 mL) was cooled to 0° C. A solution of sodium 1,1,1,3,3,3-hexamethyldisilazan-2-ide (1M solution in THF, 5.7 mL, 5.7 mmol) was added dropwise. The reaction mixture was stirred for 20 minutes at the same temperature, and then allowed to warm to room temperature and stirred for 4 hours. The reaction was quenched with saturated aqueous NH4Cl solution and extracted with EtOAc (3×20 mL). The combined organic extracts were washed with 1N aqueous citric acid solution (3×15 mL), then brine (3×15 mL). The organic phase was dried over Na2SO4, filtered, and concentrated in vacuo to give a crude product as yellow oil which was purified by silica gel column chromatography eluting with 0-20% EtOAc in heptane to give the title compound (505 mg, 44%) as colourless oil.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([O:23][C:24]2[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:26][N:25]=2)[CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12]1[S:13][CH:14]([CH2:17][C:18](OCC)=[O:19])[CH2:15][N:16]=1)=[CH:8]2.[BH4-].[Li+].O>O1CCCC1.CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([O:23][C:24]2[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:31])=[O:32])=[CH:26][N:25]=2)[CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12]1[S:13][CH:14]([CH2:17][CH2:18][OH:19])[CH2:15][N:16]=1)=[CH:8]2
Reactant: CCOC(=O)CC1CN=C(c2cc3cc(Oc4ccc(S(C)(=O)=O)cn4)cc(OC)c3[nH]2)S1
Agent: [BH4-]
Agent: [Li+]
Solvent: CO
Solvent: O
Solvent: C1CCOC1
Product: COc1cc(Oc2ccc(S(C)(=O)=O)cn2)cc2cc(C3=NCC(CCO)S3)[nH]c12
Temperature: 25 °C
Reaction time: 4 h
Yield: 44.6 %

Procedure:
Ethyl [2-(7-methoxy-5-{[5-(methylsulfonyl)pyridin-2-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetate (270 mg) was dissolved in a mixture of tetrahydrofuran (3 mL) and methanol (1.5 mL). Lithium borohydride (62 mg) was added to the mixture at 0° C. and the mixture was stirred at room temperature for 4 h. Water was added to the mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, filtered and concentrated. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=20/80 to 100/0, volume ratio), followed by basic silica gel column chromatography (methanol/ethyl acetate/hexane=0/20/80 to 10/90/0) to give the title compound (110 mg, 43%) as a white amorphous solid. MS 448 (MH+).
Reaction SMILES: C[O:2][C:3]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[NH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=1.C(O)(=O)C1C=CC=CC=1.[O-:27][C:28]#[N:29].[Na+]>C1(C)C=CC=CC=1>[CH:7]1[CH:8]=[CH:9][C:10]2[N:11]([C:28]([NH2:29])=[O:27])[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:17]=3[C:3](=[O:2])[CH2:4][C:5]=2[CH:6]=1
Reactant: COC1=Cc2ccccc2Nc2ccccc21
Reactant: N#C[O-]
Agent: O=C(O)c1ccccc1
Agent: [Na+]
Solvent: Cc1ccccc1
Product: NC(=O)N1c2ccccc2CC(=O)c2ccccc21
Temperature: 25 °C
Yield: 40.7 %

Procedure:
A mixture of 100 gms of 10-methoxyiminostilbene in 2000 mL of toluene containing 274 gms of benzoic acid and 370 gms of sodium cyanate were heated to reflux temperature under stirring and maintained for 12 hours. The reaction mixture was then cooled to room temperature and filtered. The clear toluene filtrate was washed with 5% sodium carbonate solution followed by water. The toluene layer was then added to 1000 mL of 2N hydrochloric acid and the mixture was heated at 75-90° C. for a period of 2 hours under good agitation. It was then cooled to 0-5° C., maintained for 2 hours and the product oxcarbazepine was separated by filtration. This was then purified once in a dichloromethane:methanol mixture to furnish 46 gms of pure oxcarbazepine. Purity was determined by HPLC to be 99.45%.
Reaction SMILES: [C:1]([NH:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][C@@H:6]1[N:24]=[N+]=[N-])(=[O:3])[CH3:2]>CO.[Pd]>[C:1]([NH:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][C@@H:6]1[NH2:24])(=[O:3])[CH3:2]
Reactant: CC(=O)N[C@@H]1[C@@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H](COC(C)=O)O[C@@H]1N=[N+]=[N-]
Agent: [Pd]
Solvent: CO
Product: CC(=O)N[C@@H]1[C@@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H](COC(C)=O)O[C@@H]1N
Reaction time: 24 h

Procedure:
Compound 47 (1.0 g) was dissolved in 30 mL methanol and subjected to hydrogenolysis using 1.0 g of 10% Pd on activated charcoal. After 24 hr, the charcoal was removed by filtration, and the filtrate was concentrated under vacuum to give 2-acetamido-3,4,6-tri-O-acetyl-1-amino-1,2-dideoxy-a-D-galactopyranose, 48, as colorless gum (850 mg). The derivative 48 gave a positive ninhydrin test.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH2:11][CH2:12][CH2:13][S:14](=[O:18])(=[O:17])[CH2:15][CH2:16][C:5]=3[C:4]=2[CH:3]=1.[H-].[Na+].[CH3:21][N:22]([CH3:27])[CH2:23][CH2:24][CH2:25]Cl>>[CH3:21][N:22]([CH3:27])[CH2:23][CH2:24][CH2:25][N:7]1[C:8]2[CH:9]=[CH:10][C:2]([Br:1])=[CH:3][C:4]=2[C:5]2[CH2:16][CH2:15][S:14](=[O:17])(=[O:18])[CH2:13][CH2:12][CH2:11][C:6]1=2
Reactant: CN(C)CCCCl
Reactant: O=S1(=O)CCCc2[nH]c3ccc(Br)cc3c2CC1
Agent: [H-]
Agent: [Na+]
Product: CN(C)CCCn1c2c(c3cc(Br)ccc31)CCS(=O)(=O)CCC2

Procedure:
A mixture of 9.0g (0.0276 mole) of 1,2,4,5,6,7-hexahydro-10-bromothiocino[5,4-b]indole 3,3-dioxide, 1.3g (0.03 mole) of 57% dispersion sodium hydride and 3.36g (0.0276 mole) of 3-dimethylaminopropyl chloride is treated according to the procedure in Example 6. After recrystallization from ethyl acetate, there is obtained 6.0g (52%) of an analytical sample, m.p. 135°-137° C.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.Cl[C:7]1[N:8]=[C:9]([NH:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([N+:25]([O-:27])=[O:26])[CH:20]=2)[C:10]2[C:15]([CH3:16])=[CH:14][S:13][C:11]=2[N:12]=1>>[N:1]1([C:7]2[N:8]=[C:9]([NH:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([N+:25]([O-:27])=[O:26])[CH:20]=3)[C:10]3[C:15]([CH3:16])=[CH:14][S:13][C:11]=3[N:12]=2)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: Cc1csc2nc(Cl)nc(NCc3cccc([N+](=O)[O-])c3)c12
Reactant: c1c[nH]cn1
Product: Cc1csc2nc(-n3ccnc3)nc(NCc3cccc([N+](=O)[O-])c3)c12

Procedure:
Following the procedure of Example 97, the reaction of imidazole with 2-chloro-5-methyl-4-(3-nitrobenzylamino)-thieno-[2,3-d]-pyrimidine gives 2-(imidazol-1-yl)-5-methyl-4-(3-nitrobenzylamino)-thieno-[2,3-d]-pyrimidine.
Reaction SMILES: [CH2:1]([C:8]1[CH:9]=[C:10]([CH:13]=[CH:14][CH:15]=1)[CH:11]=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+].O.C(OCC)C>CO>[CH2:1]([C:8]1[CH:9]=[C:10]([CH:13]=[CH:14][CH:15]=1)[CH2:11][OH:12])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=Cc1cccc(Cc2ccccc2)c1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: CCOCC
Solvent: O
Product: OCc1cccc(Cc2ccccc2)c1
Temperature: 0 °C
Reaction time: 1 h
Yield: 93.6 %

Procedure:
3-Benzylbenzaldehyde (5.5 g) was dissolved in methanol (75 cm3) and cooled to 0° C. Sodium borohydride (1.29 g) was added gradually in small portions, and stirring was continued for one hour. The reaction mixture was cautiously poured into a water/diethyl ether mixture, and the resulting ethereal solution was washed with water and brine, and dried over anhydrous magnesium sulphate. Evaporation of the solvents under reduced pressure gave 3-benzylbenzyl alcohol as a pale yellow oil (5.2 g). The product was used without further purification.
Reaction SMILES: [N:1]1([S:6]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([O:15]CC3C=CC=CC=3)[N:10]=2)(=[O:8])=[O:7])[CH:5]=[CH:4][CH:3]=[CH:2]1.ClCCl.FC(F)(F)C(O)=O>C1(C)C=CC=CC=1>[N:1]1([S:6]([C:9]2[NH:10][C:11](=[O:15])[CH:12]=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH:2]=[CH:3][CH:4]=[CH:5]1
Reactant: O=S(=O)(c1cccc(OCc2ccccc2)n1)n1cccc1
Solvent: O=C(O)C(F)(F)F
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: O=c1cccc(S(=O)(=O)n2cccc2)[nH]1

Procedure:
The organic washings were combined, dried over anhydrous magnesium sulphate and the solvent evaporated under reduced pressure to give a crude product identified as 2-(pyrrole-1-sulphonyl)-6-benzyloxypyridine. The crude product was treated with dichloromethane (5 cm3) and trifluoroacetic acid (5 cm3) for 24 hours at the ambient temperature. Toluene (10 cm3) was added and the reaction mixture evaporated to dryness under reduced pressure. The crude product was purified by silica chromatography eluting with 30% ethyl acetate in hexane.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:26])[C:5]([OH:25])=[C:6]([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[C:7]2=[O:12].[O:27]1CC[CH2:29][CH2:28]1.[H-].[Na+].C(Cl)(=O)C>C(Cl)Cl>[C:28]([O:25][C:5]1[C:4](=[O:26])[C:3]2[C:8](=[CH:9][CH:10]=[CH:11][C:2]=2[Cl:1])[C:7](=[O:12])[C:6]=1[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])(=[O:27])[CH3:29]
Reactant: CCCCCCCCCCCCC1=C(O)C(=O)c2c(Cl)cccc2C1=O
Reactant: C1CCOC1
Agent: [H-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CC(=O)Cl
Product: CCCCCCCCCCCCC1=C(OC(C)=O)C(=O)c2c(Cl)cccc2C1=O
Temperature: 25 °C

Procedure:
A solution of 0.95 parts of 5-chloro-2-dodecyl-3-hydroxy-1,4-naphthoquinone in 20 parts of anhydrous tetrahydrofuran was added under nitrogen to a mixture of 0.0635 parts of dispersed sodium hydride in 40 parts of tetrahydrofuran with stirring at room temperature. After 45 minutes of stirring, a solution of 0.275 parts of acetyl chloride in 30 parts of tetrahydrofuran was added and the mixture stirred for 5 hours. The tetrahydrofuran was stripped under reduced pressure and the residue taken up in methylene chloride and then washed with water, 10% hydrochloric acid, four more times with water, dried over sodium sulfate and stripped. The resulting yellow solid was purified by column chromatography on silica gel using 1-chlorobutane as eluent. Solvent removal gave 0.9 parts of 3-acetoxy-5-chloro-2-dodecyl-1,4-naphthoquinone, m.p. 57°-59° C.
Reaction SMILES: [S:1]1[CH:5]=[C:4]([NH:6][C:7](=[O:13])[O:8][C:9]([CH3:12])([CH3:11])[CH3:10])[N:3]=[CH:2]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[F:24][C:25]1[CH:30]=[C:29]([F:31])[C:28]([F:32])=[CH:27][C:26]=1[S:33](Cl)(=[O:35])=[O:34]>O1CCCC1.C(OCC)(=O)C>[S:1]1[CH:5]=[C:4]([N:6]([S:33]([C:26]2[CH:27]=[C:28]([F:32])[C:29]([F:31])=[CH:30][C:25]=2[F:24])(=[O:35])=[O:34])[C:7](=[O:13])[O:8][C:9]([CH3:10])([CH3:12])[CH3:11])[N:3]=[CH:2]1
Reactant: O=S(=O)(Cl)c1cc(F)c(F)cc1F
Reactant: CC(C)(C)OC(=O)Nc1cscn1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N(c1cscn1)S(=O)(=O)c1cc(F)c(F)cc1F
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 62 %

Procedure:
A solution of tert-butyl thiazol-4-ylcarbamate (3.46 g, 17.3 mmol) in tetrahydrofuran (150 mL) at −78° C. was treated with lithium bis(trimethylsilyl)amide (1.0 M solution in tetrahydrofuran, 20.8 mL, 20.8 mmol). The resulting mixture was stirred at −78° C. for 0.5 h, allowed to warm to ambient temperature and stirred for a further 0.5 h. The reaction mixture was cooled to −78° C. and treated with a solution of 2,4,5-trifluorobenzene-1-sulfonyl chloride (3.99 g, 17.3 mmol) in tetrahydrofuran (30 mL). The resulting mixture was stirred at −78° C. for 4 h, allowed to warm to ambient temperature and stirred for a further 16 h. The reaction mixture was diluted with ethyl acetate (300 mL) and washed with saturated aqueous ammonium chloride (2×150 mL) and brine (2×150 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluting with a gradient of ethyl acetate in hexanes to afford tert-butyl thiazol-4-yl((2,4,5-trifluorophenyl)sulfonyl)carbamate as a beige solid in 62% yield (4.23 g): 1H NMR (300 MHz, CDCl3) δ 8.79-8.75 (m, 1H), 8.06-7.96 (m, 1H), 7.53-7.48 (m, 1H), 7.15-7.04 (m, 1H), 1.34 (s, 9H); MS (ES+) m/z 394.7 (M+1).
Reaction SMILES: C([O:4][CH:5]1[CH2:10][CH:9]2[CH2:11][C:6]1([CH3:12])[CH2:7][CH2:8]2)(=O)C.[H-].[Al+3].[Li+].[H-].[H-].[H-].S(=O)(=O)(O)O>C(OCC)C>[CH3:12][C:6]12[CH2:11][CH:9]([CH2:8][CH2:7]1)[CH2:10][CH:5]2[OH:4]
Reactant: CC(=O)OC1CC2CCC1(C)C2
Agent: O=S(=O)(O)O
Agent: [Al+3]
Agent: [H-]
Solvent: CCOCC
Product: CC12CCC(CC1O)C2
Temperature: 25 °C
Yield: 96 %

Procedure:
290.0 g (1.73M) of the acetate (III) obtained in 1-2) above dissolved in 300 ml of absolute diethyl ether was added to 65.2 g (1.7M) of lithium aluminum hydride suspended in 800 ml of absolute diethyl ether at room temperature under a nitrogen gas stream. Then the resulting mixture was heated under reflux for six hours and stirred at room temperature over night. Subsequently 500 ml of a 5% aqueous solution of sulfuric acid was slowly added to the reaction mixture with stirring under ice-cooling. The ether phase was collected and dried over anhydrous magnesium sulfate. After evaporation of the ether, the residue was distilled under reduced pressure to give 209 g (theoretical yield: 96%) of the aimed compound (IV) as a colorless oily material. b.p.: 83° C./20 mmHg.