Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:5]1[C:9](=[O:10])[C:8]2=[C:11]([CH3:15])[CH:12]=[CH:13][CH:14]=[C:7]2[C:6]1=[O:16])[CH:2]([CH3:4])[CH3:3].O>CO.[BH4-].[K+]>[CH3:15][C:11]1[CH:12]=[CH:13][CH:14]=[C:7]2[C:8]=1[C:9](=[O:10])[N:5]([CH2:1][CH:2]([CH3:3])[CH3:4])[CH:6]2[OH:16].[CH3:15][C:11]1[CH:12]=[CH:13][CH:14]=[C:7]2[C:8]=1[CH:9]([OH:10])[N:5]([CH2:1][CH:2]([CH3:3])[CH3:4])[C:6]2=[O:16]
Reactant: Cc1cccc2c1C(=O)N(CC(C)C)C2=O
Agent: [BH4-]
Agent: [K+]
Solvent: O
Solvent: CO
Product: Cc1cccc2c1C(=O)N(CC(C)C)C2O
Product: Cc1cccc2c1C(O)N(CC(C)C)C2=O
Temperature: 20 °C
Reaction time: 65 h

Procedure:
4-Methyl-3-hydroxy-2-isobutyl-2,3-dihydroisoindol-1-one and 7-methyl-3-hydroxy-2-isobutyl-2,3-dihydroisoindol-1-one are prepared as described in Example 1, starting with 5.4 g of N-isobutyl-3-methylphthalimide in 20 cm3 of methanol and 1.4 g of potassium borohydride. The reaction mixture is stirred at a temperature in the region of 20° C. for 65 hours and is then cooled to a temperature in the region of 0° C. and 10 cm3 of distilled water are added dropwise. The mixture is concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. and the residue is taken up successively in diethyl ether and then in dichloromethane. The precipitate obtained is filtered off and the filtrate is then concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue is purified by chromatography under argon pressure (50 kPa) on a column of silica gel (particle size 15-40 μm), eluting with a mixture of cyclohexane/ethyl acetate (70/30 by volume). The fractions comprising each expected product are combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The fractions comprising a mixture of the two expected products are combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. The residue is purified again by chromatography under argon pressure (50 kPa) on a column of silica gel (particle size 15-40 μm), eluting with a mixture of cyclohexane/ethyl acetate (80/20 by volume). The fractions comprising each expected product are combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature in the region of 40° C. 0.74 g of 7-methyl-3-hydroxy-2-isobutyl-2,3-dihydroisoindol-1-one in the form of a white powder (Rf=0.54, thin layer chromatography on silica gel, eluent: cyclohexane/ethyl acetate (50/50 by volume)) and 0.89 g of 4-methyl-3-hydroxy-2-isobutyl-2,3-dihydroisoindol-1-one in the form of a cottony white solid (Rf=0.40, thin layer chromatography on silica gel, eluent: cyclohexane/ethyl acetate (50/50 by volume)) are thus obtained.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:6]=[CH:7][C:8]3[C:13]([C:14]=2[CH:15]=1)=[CH:12][CH:11]=[C:10]([CH2:16][O:17]C(=O)C)[CH:9]=3.[H-].C([Al+]CC(C)C)C(C)C.CCCCCC.Cl>C1COCC1.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[CH:6]=[CH:7][C:8]3[C:13]([C:14]=2[CH:15]=1)=[CH:12][CH:11]=[C:10]([CH2:16][OH:17])[CH:9]=3
Reactant: CC(=O)OCc1ccc2c(ccc3ccc(Br)cc32)c1
Agent: CC(C)C[Al+]CC(C)C
Agent: Cl
Agent: [H-]
Solvent: CCCCCC
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: OCc1ccc2c(ccc3ccc(Br)cc32)c1
Reaction time: 0.5 h
Yield: 99.4 %

Procedure:
A solution of 3-bromo-7-(acetoxymethyl)phenanthrene (2.042 g, 6.20 mmol) in 50 ml of THF was cooled to 0° C. and a solution of diisobutylaluminum hydride in hexane (1.0M, 14 ml, 14 mmol) was added dropwise. After 30 minutes, the solution was cautiously hydrolyzed with 1N HCl and was then diluted with ethyl acetate and washed successively with 1N HCl, sat. NaHCO3, H2O, and brine. Drying (MgSO4) and evaporation gave 1.77 g (99%) of the title compound as a white solid which was used in the next reaction without purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH:15]1[CH2:17][O:16]1)[N:9]=[CH:8][CH:7]=[C:6]2[O:18][C:19]1[C:20]([CH3:29])=[N:21][C:22]2[C:27]([CH:28]=1)=[CH:26][N:25]=[CH:24][CH:23]=2.FC(F)(F)C(O)=[O:33].[OH-].[Na+].O>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH:15]([OH:33])[CH2:17][OH:16])[N:9]=[CH:8][CH:7]=[C:6]2[O:18][C:19]1[C:20]([CH3:29])=[N:21][C:22]2[C:27]([CH:28]=1)=[CH:26][N:25]=[CH:24][CH:23]=2
Reactant: O=C(O)C(F)(F)F
Reactant: COc1cc2c(Oc3cc4cnccc4nc3C)ccnc2cc1OCC1CO1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: ClCCl
Product: COc1cc2c(Oc3cc4cnccc4nc3C)ccnc2cc1OCC(O)CO
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 15 %

Procedure:
3-(6-Methoxy-7-oxiranylmethoxy-quinolin-4-yloxy)-2-methyl-[1,6]naphthyridine (44 mg) was dissolved in methylene chloride (2 ml) to prepare a solution which was brought to 0° C. Trifluoroacetic acid (0.4 ml) was added thereto, and the mixture was stirred at 0° C. for 30 min and then at room temperature for 4 hr. The reaction solution was brought to 0° C., was stirred, and was made alkaline by the addition of a 10% aqueous sodium hydroxide solution. Water was added thereto, and the mixture was extracted with chloroform. The chloroform layer was then washed with saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by thin layer chromatography using chloroform-methanol to give the title compound (7 mg, yield 15%).
Reaction SMILES: [C:1]1(=[O:11])[NH:5][C:4](=[O:6])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.[K].[CH3:13][O:14][C:15](=[O:28])[C:16]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][CH2:25]Cl)=[C:18](C)[CH:17]=1.O.CN(C)[CH:32]=[O:33]>>[CH3:13][O:14][C:15](=[O:28])[C:16]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][CH2:25][N:5]2[C:1](=[O:11])[C:2]3[C:3](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:4]2=[O:6])=[C:18]([O:33][CH3:32])[CH:17]=1
Reactant: CN(C)C=O
Reactant: COC(=O)c1ccc(OCCCCl)c(C)c1
Reactant: O=C1NC(=O)c2ccccc21
Agent: [K]
Solvent: O
Product: COC(=O)c1ccc(OCCCN2C(=O)c3ccccc3C2=O)c(OC)c1
Yield: 80 %

Procedure:
A mixture of 66.9 g (0.354 mole) of potassium phthalimide (98%, Aldrich) and 90.0 g (0.348 mole) of 4-(3-chloropropoxy)-3-methyl benzoic acid methyl ester in 450 mL of dimethyl formamide was stirred and heated at reflux for 5 hr then let stir at ambient temperature overnight. The reaction mixture was treated with 3 L of water and the resulting solid was collected by filtration to give 108.5 g (84%) of crude title compound. An 8.0 g sample of this solid was recrystallized from 2-propanol to yield 6.4 g (80%) of title compound as a white solid, mp 127°-128° C.
Reaction SMILES: O[CH2:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[CH:6]=[O:7].[NH2:11][C:12]1[S:13][C:14]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:15]=2[N:16]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[F:21][C:18]1[CH:19]=[CH:20][C:14]2[S:13][C:12]([NH:11][CH2:2][C:3]3[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=3)[CH2:6][OH:7])=[N:16][C:15]=2[CH:17]=1
Reactant: O=Cc1cccc(CO)c1
Reactant: Nc1nc2cc(F)ccc2s1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: OCc1cccc(CNc2nc3cc(F)ccc3s2)c1
Temperature: 0 °C
Reaction time: 2 h
Yield: 68.6 %

Procedure:
A mixture of 1.38 g of 3-hydroxymethylbenzaldehyde, 1.7 g of 2-amino-5-fluorobenzothiazole and 200 mg of p-toluene sulfonic acid in 100 ml of toluene were refluxed with a Dean-Stark trap for 18 hours. The reaction mixture was concentrated in vacuo and the residue dissolved in 50 ml of dry tetrahydrofuran and 50 ml of methanol and cooled to 0° C. To the resulting solution was added 945 mg of sodium borohydride over a period of 20 minutes. The reaction mixture was stirred at 0° C. for 2 hours, was hydrolyzed by the addition of an ammonium chloride solution and was concentrated to a small volume in vacuo. The residual suspension was added to 200 ml of water, the pH adjusted to 10 and the resulting mixture extracted with ethyl acetate (2×200 ml). The extracts were combined, washed with water and a brine solution and dried over magnesium sulfate. Removal in vacuo of the solvent gave 2 g of material which was chromatographed on silica gel to give 235 mg of pure product.
Reaction SMILES: [CH2:1]1[NH:6][CH2:5][CH2:4][N:3]2[C:7](=[O:10])[CH2:8][CH2:9][C@H:2]12.CS(O[CH:16]1[CH2:19][N:18]([CH:20]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:17]1)(=O)=O.C(N(CC)CC)C>C(#N)C>[C:21]1([CH:20]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[N:18]2[CH2:19][CH:16]([N:6]3[CH2:5][CH2:4][N:3]4[C:7](=[O:10])[CH2:8][CH2:9][C@@H:2]4[CH2:1]3)[CH2:17]2)[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1
Reactant: CS(=O)(=O)OC1CN(C(c2ccccc2)c2ccccc2)C1
Reactant: O=C1CC[C@@H]2CNCCN12
Solvent: CCN(CC)CC
Solvent: CC#N
Product: O=C1CC[C@@H]2CN(C3CN(C(c4ccccc4)c4ccccc4)C3)CCN12
Temperature: 150 °C
Yield: 53 %

Procedure:
(8aR)-Hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one (see WO 03/066635; 0.17 g, 1.2 mmol), 1-(diphenylmethyl)azetidin-3-yl methanesulfonate (see J. Org. Chem.; 56; 1991; 6729; 0.40 g, 1.3 mmol) and triethylamine (0.20 mL, 1.4 mmol) were dissolved in acetonitrile. The mixture was heated for 15 min at 150° C. using microwave single node heating and then the solvent was removed by evaporation. The residue was partitioned between ethyl acetate and aqueous NaHCO3 and the aqueous phase extracted further with ethyl acetate. The organic phase was dried and then the solvent was removed by evaporation. The product was purified by chromatography on silica gel (methanol-methylene chloride 5:95). There was obtained 0.23 g (54%) of (8aR)-2-[1-(diphenylmethyl)azetidin-3-yl]hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one as a pale yellow oil. 1H NMR (500 MHz, CDCl3): 1.5-1.6 (m, 2H), 1.7-1.8 (m, 1H), 2.1-2.2 (m, 1H), 2.3-2.4 (m, 2H), 2.6-2.7 (d, 1H), 2.8 (m, 1H), 2.8-2.9 (m, 3H), 3.0 (qn, 1H), 3.4 (t, 2H), 3.6 (m, 1H), 4.0 (d, 1H), 4.4 (s, 1H), 7.2 (m, 2H), 7.2-7.3 (m, 4H), 7.4 (m, 4H); LCMS: m/z 362 (M+1)+.
Reaction SMILES: [N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C@@H:3]([NH:9][C:10]([C:12]1[O:13][C:14]3[CH:20]=[C:19]([N+:21]([O-])=O)[CH:18]=[CH:17][C:15]=3[CH:16]=1)=[O:11])[CH2:2]2>[Sn](Cl)Cl.CN(C=O)C>[NH2:21][C:19]1[CH:18]=[CH:17][C:15]2[CH:16]=[C:12]([C:10]([NH:9][C@@H:3]3[CH:4]4[CH2:7][CH2:8][N:1]([CH2:6][CH2:5]4)[CH2:2]3)=[O:11])[O:13][C:14]=2[CH:20]=1
Reactant: O=C(N[C@H]1CN2CCC1CC2)c1cc2ccc([N+](=O)[O-])cc2o1
Agent: Cl[Sn]Cl
Solvent: CN(C)C=O
Product: Nc1ccc2cc(C(=O)N[C@H]3CN4CCC3CC4)oc2c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
1.55 g (4.92 mmol) of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-6-nitro-1-benzofuran-2-carboxamide are dissolved in 15 ml of 2 M tin(II) chloride solution in DMF and stirred at room temperature overnight. Dowex 50WX2-200 ion exchanger resin is added and, within 1 h, the mixture is concentrated in a rotary evaporator. The resin is washed successively with water, DMF, methanol, dichloromethane, methanol and 10% triethylamine in methanol. The product fraction is concentrated and chromatographed on silica gel (mobile phase: dichloromethane/methanol/triethylamine). Concentration in vacuo results in 642.8 mg (45.8% of theory) of the title compound.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:13])=[N:11][N:12]=2)=[CH:4][C:3]=1[C:14]1[CH:19]=[CH:18][C:17]([C:20](O)=[O:21])=[CH:16][CH:15]=1.[NH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C:30]1[CH:35]=[CH:34][C:33]([S:36]([NH2:39])(=[O:38])=[O:37])=[CH:32][CH:31]=1>>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]([CH3:13])=[N:11][N:12]=2)=[CH:4][C:3]=1[C:14]1[CH:15]=[CH:16][C:17]([C:20]([NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=2[C:30]2[CH:35]=[CH:34][C:33]([S:36](=[O:38])(=[O:37])[NH2:39])=[CH:32][CH:31]=2)=[O:21])=[CH:18][CH:19]=1
Reactant: Nc1ccccc1-c1ccc(S(N)(=O)=O)cc1
Reactant: Cc1nnc(-c2ccc(C)c(-c3ccc(C(=O)O)cc3)c2)o1
Product: Cc1nnc(-c2ccc(C)c(-c3ccc(C(=O)Nc4ccccc4-c4ccc(S(N)(=O)=O)cc4)cc3)c2)o1

Procedure:
2′-Methyl-5′-(5-methyl-1,3,4-oxadiazol-2-yl)-N-[2-(4-sulphamoylphenyl)phenyl]-1,1′-biphenyl-4-carboxamide was prepared from 2′-methyl-5′-(5-methyl-1,3,4-oxadiazol-2-yl)-1,1′-biphenyl-4-carboxylic acid and 4-(2-aminophenyl)phenylsulphonamide using method I. LCMS; retention time 3.16 min, MH+ 525.
Reaction SMILES: [CH3:1][N:2]([CH3:30])[C:3]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:8][CH2:7][CH:6]([C:9]2[NH:10][C:11]3[C:16]([C:17]=2[CH:18](CC)[C:19](O)=O)=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH2:5][CH2:4]1.[Si]([Cl:35])(C)(C)C.[C:36]([O:39]CC)(=[O:38])[CH3:37]>>[ClH:35].[CH3:30][N:2]([CH3:1])[C:3]1([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:4][CH2:5][CH:6]([C:9]2[NH:10][C:11]3[C:16]([C:17]=2[CH2:18][CH2:19][CH2:37][C:36]([OH:39])=[O:38])=[CH:15][CH:14]=[CH:13][CH:12]=3)[CH2:7][CH2:8]1
Reactant: CCOC(C)=O
Reactant: C[Si](C)(C)Cl
Reactant: CCC(C(=O)O)c1c(C2CCC(c3ccccc3)(N(C)C)CC2)[nH]c2ccccc12
Product: CN(C)C1(c2ccccc2)CCC(c2[nH]c3ccccc3c2CCCC(=O)O)CC1
Product: Cl
Reaction time: 16 h

Procedure:
4-[(2-(4-Dimethylamino-4-phenylcyclohexyl)-1H-indol-3-yl)butanoic acid (340 mg, 0.81 mmol) was dissolved in ethyl acetate (50 ml). Me3SiCl (207 μl, 1.62 mmol) was then added dropwise at RT and the mixture was stirred for 16 h. The solvent distilled off on a rotary evaporator. Example 172 (370 mg, m.p. 227-230° C., 100%) was a beige-coloured solid.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6](S(C)=O)[C:5]([C:11]#[N:12])=[C:4]([C:13]2[S:14][CH:15]=[CH:16][CH:17]=2)[N:3]=1.[CH3:18][O:19][CH2:20][CH2:21][NH2:22]>O1CCOCC1>[NH2:1][C:2]1[N:7]=[C:6]([NH:22][CH2:21][CH2:20][O:19][CH3:18])[C:5]([C:11]#[N:12])=[C:4]([C:13]2[S:14][CH:15]=[CH:16][CH:17]=2)[N:3]=1
Reactant: COCCN
Reactant: CS(=O)c1nc(N)nc(-c2cccs2)c1C#N
Solvent: C1COCCO1
Product: COCCNc1nc(N)nc(-c2cccs2)c1C#N

Procedure:
From 2-amino-4-methanesulfinyl-6-thiophen-2-yl-pyrimidine-5-carbonitrile and 2-methoxyethylamine in dioxane. ES-MS m/e (%): 276 (M+H+, 100).
Reaction SMILES: [CH3:1][C:2]([CH3:25])([CH3:24])[C:3]([C:5]1[C:13]2[C:8](=[N:9][CH:10]=[C:11]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([Si](C)(C)C)[CH:15]=3)[N:12]=2)[NH:7][CH:6]=1)=[O:4].C(=O)([O-])[O-].[K+].[K+].[I:32]Cl>C(Cl)Cl.[Al]>[I:32][C:16]1[CH:15]=[C:14]([C:11]2[N:12]=[C:13]3[C:5]([C:3](=[O:4])[C:2]([CH3:25])([CH3:24])[CH3:1])=[CH:6][NH:7][C:8]3=[N:9][CH:10]=2)[CH:19]=[CH:18][CH:17]=1
Reactant: CC(C)(C)C(=O)c1c[nH]c2ncc(-c3cccc([Si](C)(C)C)c3)nc12
Reactant: ClI
Agent: O=C([O-])[O-]
Agent: [Al]
Agent: [K+]
Solvent: ClCCl
Product: CC(C)(C)C(=O)c1c[nH]c2ncc(-c3cccc(I)c3)nc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 81 %

Procedure:
2,2-Dimethyl-1-[2-(3-trimethylsilanyl-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-propan-1-one (250 mg, 0.71 mmol) was suspended in 7 ml of methylene chloride and potassium carbonate (393 mg, 2.8 mmol) was added. The flask was wrapped in aluminum foil and iodine monochloride (2.5 ml of a 1M solution in methylene chloride) was added dropwise. The mixture was stirred in the dark at room temperature for one hour. The reaction was quenched with 10% aqueous sodium thiosulfate, extracted into methylene chloride, and washed with water two times. The organic layer was dried with sodium sulfate, concentrated, triturated with ethyl ether, filtered and dried in a vacuum oven to give 232 mg (81%) of 1-[2-(3-iodo-phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2,-dimethyl-propan-1-one as a yellow solid. (M+H)+=406.
Reaction SMILES: C[O-].[Na+].Cl.[NH2:5][C:6]([NH2:8])=[NH:7].O1CCCC1.Cl.[Cl:15][C:16]([C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[N:20]([C:27]2[C:36]3[C:31](=[C:32]([C:37]([F:40])([F:39])[F:38])[CH:33]=[CH:34][CH:35]=3)[N:30]=[CH:29][CH:28]=2)[CH:19]=1)=[O:17]>CO.ClCCl>[ClH:15].[NH:7]([C:16]([C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[N:20]([C:27]2[C:36]3[C:31](=[C:32]([C:37]([F:39])([F:38])[F:40])[CH:33]=[CH:34][CH:35]=3)[N:30]=[CH:29][CH:28]=2)[CH:19]=1)=[O:17])[C:6]([NH2:8])=[NH:5]
Reactant: N=C(N)N
Reactant: O=C(Cl)c1cn(-c2ccnc3c(C(F)(F)F)cccc23)c2ccccc12
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Solvent: ClCCl
Product: N=C(N)NC(=O)c1cn(-c2ccnc3c(C(F)(F)F)cccc23)c2ccccc12
Temperature: 25 °C
Reaction time: 1 h

Procedure:
20 cm3 of methanol and 14 cm3 (7 mmol) of a 0.5M solution of sodium methoxide in methanol are added to 0.67 g (7 mmol) of guanidine hydrochloride under an argon atmosphere. After stirring at a temperature in the region of 25° C. for 1 hour, the reaction mixture is concentrated to dryness under reduced pressure (2.7 kPa) and the residue is three times successively dissolved in 20 cm3 of dichloromethane and evaporated to dryness under reduced pressure (2.7 kPa). 30 cm3 of tetrahydrofuran and 0.525 g (1.4 mmol) of 3-chlorocarbonyl-1-(8-(trifluoromethyl)quinol-4-yl)-1H-indole hydrochloride, suspended in 30 cm3 of dichloromethane, are subsequently added thereto under an argon atmosphere. After stirring at a temperature in the region of 20° C. for 16 hours, the reaction mixture is concentrated to give a solid which is purified by flash chromatography [eluent: ethyl acetate/methanol (9/1 and then 8/2 by volume)]. After concentrating the fractions to dryness under reduced pressure (2.7 kPa), the product obtained is triturated in 20 cm3 of diisopropyl ether and filtered off, resulting in 0.14 g of 3-guanidinocarbonyl-1-(8-(trifluoromethyl)quinol-4-yl)-1H-indole hydrochloride in the form of a white powder melting at 212° C. Mass spectrum (EI): m/e 397 (M+•), m/e 339 (base peak).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:14]=[CH:13][C:6]([O:7][C:8]2[S:9][CH:10]=[CH:11][N:12]=2)=[CH:5][CH:4]=1.C([Li])CCC.[CH2:20]([Sn:24](Cl)([CH2:29][CH2:30][CH2:31][CH3:32])[CH2:25][CH2:26][CH2:27][CH3:28])[CH2:21][CH2:22][CH3:23].C(=O)=O>O1CCCC1>[CH3:1][O:2][C:3]1[CH:14]=[CH:13][C:6]([O:7][C:8]2[S:9][C:10]([Sn:24]([CH2:25][CH2:26][CH2:27][CH3:28])([CH2:29][CH2:30][CH2:31][CH3:32])[CH2:20][CH2:21][CH2:22][CH3:23])=[CH:11][N:12]=2)=[CH:5][CH:4]=1
Reactant: COc1ccc(Oc2nccs2)cc1
Reactant: CCCC[Sn](Cl)(CCCC)CCCC
Agent: O=C=O
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CCCC[Sn](CCCC)(CCCC)c1cnc(Oc2ccc(OC)cc2)s1
Reaction time: 1 h
Yield: 90.2 %

Procedure:
To a solution of Example 11A (3.27 g, 15.8 mmol) in tetrahydrofuran (30 mL) was added n-butyl lithium (2.5 M in hexanes, 6.50 mL, 16.3 mmol, 1.0 eq.) at −78° C. The mixture was stirred for 1 hour. Tributyltin chloride (4.40 mL, 16.3 mmol, 1.0 eq) was then added at −78° C. (The dry ice bath was removed and the mixture was stirred for 1 hour. The reaction was quenched with water (100 mL). The aqueous layer was extracted with ether and the organic layer washed with brine, dried over MgSO4 and concentrated. The residue was purified on silica gel eluting with ethyl acetate: hexane gradient (0-20%) to give the title compound (7.07 g, 92%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[Cl:22])[O:5][CH:6]1[CH2:11][CH2:10][N:9]([CH2:12][CH2:13][CH2:14][C:15]([O:17]C)=[O:16])[CH2:8][CH2:7]1.CO>Cl>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[Cl:22])[O:5][CH:6]1[CH2:7][CH2:8][N:9]([CH2:12][CH2:13][CH2:14][C:15]([OH:17])=[O:16])[CH2:10][CH2:11]1
Reactant: COC(=O)CCCN1CCC(Oc2ccc(Cl)c(Cl)c2)CC1
Agent: Cl
Solvent: CO
Product: O=C(O)CCCN1CCC(Oc2ccc(Cl)c(Cl)c2)CC1
Yield: 180 %

Procedure:
Methyl 4-(3,4-dichlorophenoxy)-1-piperidinebutanoate (0.48 g) was dissolved in HCl solution (6M, 10 mL) and methanol (1 mL) was added. The reaction mixture was heated under reflux for 8 days. The solvents were evaporated to give the title compound (0.46 g).
Reaction SMILES: [C:1]([O: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[O:24][C:25]1[C:29]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH2:39][C:40](O)=[O:41])=[CH:33][C:32]=2[CH3:43])=[C:28]([CH:44]([CH3:46])[CH3:45])[NH:27][N:26]=1)(=[O:3])[CH3:2].Cl.[NH2:48][C:49]([CH3:61])([CH3:60])[C:50]([O:52][CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)=[O:51].ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.O.C(N(CC)CC)C>[C:1]([O: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[O:24][C:25]1[C:29]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH2:39][C:40](=[O:41])[NH:48][C:49]([C:50]([O:52][CH2:53][C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)=[O:51])([CH3:61])[CH3:60])=[CH:33][C:32]=2[CH3:43])=[C:28]([CH:44]([CH3:46])[CH3:45])[NH:27][N:26]=1)(=[O:3])[CH3:2]
Reactant: CC(C)(N)C(=O)OCc1ccccc1
Reactant: CC(=O)OC[C@H]1O[C@@H](Oc2n[nH]c(C(C)C)c2Cc2ccc(OCCC(=O)O)cc2C)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CC(=O)OC[C@H]1O[C@@H](Oc2n[nH]c(C(C)C)c2Cc2ccc(OCCC(=O)NC(C)(C)C(=O)OCc3ccccc3)cc2C)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Temperature: 25 °C
Reaction time: 4 h
Yield: 84.4 %

Procedure:
To a solution of 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-4-{[4-(2-carboxyethoxy)-2-methylphenyl]methyl}-5-isopropyl-1H-pyrazole (0.14 g) in N,N-dimethylformamide (3 mL) were added benzyl 2-amino-2-methylpropionate hydrochloride (57 mg), 1-hydroxybenzotriazole (31 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (60 mg) and triethylamine (0.087 mL), and the mixture was stirred at room temperature for 4 hours. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: dichloromethane/methanol=40/1-20/1) to give the title compound (0.15 g).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH2:9][C@@H:10]1[CH2:16][CH2:15][C@@H:14]2[CH2:17][N:11]1[C:12](=[O:26])[N:13]2[O:18]CC1C=CC=CC=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H][H]>[Pd].CO>[C:1]([O:5][C:6]([NH:8][CH2:9][C@@H:10]1[CH2:16][CH2:15][C@@H:14]2[CH2:17][N:11]1[C:12](=[O:26])[N:13]2[OH:18])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)NC[C@@H]1CC[C@@H]2CN1C(=O)N2OCc1ccccc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: CC(C)(C)OC(=O)NC[C@@H]1CC[C@@H]2CN1C(=O)N2O

Procedure:
The compound (V) was reacted with triphenylphosphine (PPh3) in a suitable solvent such as tetrahydrofuran followed by addition of a catalytic amount of water to provide corresponding amine. This amino compound was further treated in situ with di-tert-butyl dicarbonate ((Boc)2O) in presence of a suitable base such as triethylamine to provide an amino protected compound, (2S, 5R)-2-(tert-butoxycarbonylaminomethyl)-6-benzyloxy-7-oxo-1, 6-diaza-bicyclo[3.2.1] octane (VI). The intermediate compound of Formula (VI) was subjected to hydrogenolysis using a catalyst such as 5% or 10% Palladium on carbon in presence of a hydrogen source such as hydrogen gas and in a suitable solvent such as methanol to provide debenzylated compound, (2S, 5R)-2-(tert-butoxycarbonylaminomethy)-6-hydroxy-7-oxo-1,6-diaza-bicyclo[3.2.1] octane (VII).