Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6](=[O:31])[C:7]1[CH:12]=[CH:11][C:10]([C:13](=[O:29])/[CH:14]=[C:15](\[C:20]2[CH:25]=[C:24]([Cl:26])[C:23]([Cl:27])=[C:22]([Cl:28])[CH:21]=2)/[C:16]([F:19])([F:18])[F:17])=[CH:9][C:8]=1[CH3:30])([CH3:4])([CH3:3])[CH3:2].C(O)(=[S:34])C.C(N(CC)CC)C>C(N(CC)CC)C.ClCCl>[C:1]([O:5][C:6](=[O:31])[C:7]1[CH:12]=[CH:11][C:10]([C:13](=[O:29])[CH2:14][C:15]([SH:34])([C:20]2[CH:25]=[C:24]([Cl:26])[C:23]([Cl:27])=[C:22]([Cl:28])[CH:21]=2)[C:16]([F:17])([F:19])[F:18])=[CH:9][C:8]=1[CH3:30])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(O)=S
Reactant: Cc1cc(C(=O)/C=C(\c2cc(Cl)c(Cl)c(Cl)c2)C(F)(F)F)ccc1C(=O)OC(C)(C)C
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1cc(C(=O)CC(S)(c2cc(Cl)c(Cl)c(Cl)c2)C(F)(F)F)ccc1C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To 2-Methyl-4-[(E)-4,4,4-trifluoro-3-(3,4,5-trichloro-phenyl)-but-2-enoyl]-benzoic acid tert-butyl ester (1.29 g) was added thioacetic acid (6 eq.) and triethylamine (12 μL). The solution was stirred under argon at room temperature for 24 hours. More thioacetic acid (1 mL) and triethylamine (1 drop) were added and the solution was stirred under argon at room temperature for 72 hours. To this mixture was added a minimum of dichloromethane and then isolute. The suspension was evaporated under vacuo. The residue was purified by chromatography on silica gel (eluent: cyclohexane/dichloromethane) to give 2-Methyl-4-[4,4,4-trifluoro-3-mercapto-3-(3,4,5-trichloro-phenyl)-butyryl]-benzoic acid tert-butyl ester (573 mg).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:11]=[C:12]([S:14]([F:19])([F:18])([F:17])([F:16])[F:15])[CH:13]=1)[C:5]([N:7]([O:9][CH3:10])[CH3:8])=[O:6].[C:20](OC(=O)C)(=[O:22])[CH3:21].FC(F)(F)C(OC(=O)C(F)(F)F)=O>>[C:20]([NH:1][C:2]1[CH:3]=[C:4]([CH:11]=[C:12]([S:14]([F:19])([F:15])([F:16])([F:17])[F:18])[CH:13]=1)[C:5]([N:7]([O:9][CH3:10])[CH3:8])=[O:6])(=[O:22])[CH3:21]
Reactant: CC(=O)OC(C)=O
Reactant: CON(C)C(=O)c1cc(N)cc(S(F)(F)(F)(F)F)c1
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Product: CON(C)C(=O)c1cc(NC(C)=O)cc(S(F)(F)(F)(F)F)c1

Procedure:
3-Amino-N-methoxy-N-methyl-5-pentafluorosulfanylbenzamide (1.2 g, example 4b) was reacted analogously to example 4c) with acetic anhydride instead of with trifluoroacetic anhydride. 1.3 g of the desired compound were isolated.
Reaction SMILES: [CH2:1]([N:3]1[CH2:8][CH2:7][N:6]([C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH:12]=[C:11]([C:19]3[CH:24]=[CH:23][C:22]([O:25][C@@H:26]([CH3:48])[CH2:27][O:28]C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)=[CH:21][CH:20]=3)[N:10]=2)[CH2:5][CH2:4]1)[CH3:2].C1C=CC=CC=1.[ClH:55]>CO>[ClH:55].[ClH:55].[CH2:1]([N:3]1[CH2:8][CH2:7][N:6]([C:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH:12]=[C:11]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH:26]([CH3:48])[CH2:27][OH:28])=[CH:21][CH:20]=3)[N:10]=2)[CH2:5][CH2:4]1)[CH3:2]
Reactant: CCN1CCN(c2nc(-c3ccc(O[C@@H](C)COC(c4ccccc4)(c4ccccc4)c4ccccc4)cc3)cc3ccccc23)CC1
Agent: Cl
Solvent: c1ccccc1
Solvent: CO
Product: CCN1CCN(c2nc(-c3ccc(OC(C)CO)cc3)cc3ccccc23)CC1
Temperature: 25 °C
Reaction time: 0.75 h

Procedure:
To the resulting 1-(4-ethylpiperazin-1-yl)-3-{4-[2-trityloxy-1-(S)-methylethoxy]phenyl}isoquinoline (1.21 g) were added benzene (10 ml), methanol (50 ml) and 2N hydrochloric acid (10 ml) and dissolved, and the resulting mixture was stirred at room temperature for 45 min. The solvent was evaporated, and the resulting residue was adjusted to pH 10 by a 8N aqueous solution of sodium hydroxide, which was then extracted with ethyl acetate. The extract was washed with brine and dried over magnesium sulfate. The solvent was evaporated, to give 0.36 g of the free compound of the title compound as a colorless amorphous.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][N+:8]=2[O-])[CH:3]=[C:2]1[C:11]([O:13][CH2:14][CH3:15])=[O:12].C[Si](C)(C)N[Si](C)(C)C.[Cl:25]C(OC)=O>C1COCC1>[Cl:25][C:7]1[N:8]=[C:9]2[C:4]([CH:3]=[C:2]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[NH:1]2)=[CH:5][CH:6]=1
Reactant: CCOC(=O)c1cc2ccc[n+]([O-])c2[nH]1
Reactant: COC(=O)Cl
Agent: C[Si](C)(C)N[Si](C)(C)C
Solvent: C1CCOC1
Product: CCOC(=O)c1cc2ccc(Cl)nc2[nH]1
Temperature: 25 °C
Reaction time: 2 h
Yield: 26.4 %

Procedure:
To a stirred solution of ethyl 7-azaindole-2-carboxylate-7-oxide (1.32 g, 6.4 mmol) and hexamethyldisilazane (1.4 mL, 6.6 mmol) in THF (30 mL) at 0° C. was added dropwise over 30 min a solution of methyl chloroformate (12 mL, 15.5 mmol) in THF (5 mL). The mixture was warmed to room temperature, stirred for 2 h and partitioned between ether (50 mL) and water (50 mL). The aqueous layer was extracted with ether (30 mL). The combined organic extracts were washed (water, brine), dried (sodium sulfate) and purified by column chromatography [SiO2; heptane—ether (3:1)1 to give ethyl 6-chloro-7-azaindole-2-carboxylate as a white solid (0.38 g, 26%). mp 144-145° C. Found: C, 53.69; H, 4.05; N, 12.39%. C10H9N2ClO2 requires: C, 53.47; H, 4.04; N, 12.46%.
Reaction SMILES: [CH:1]([O:4][C:5]1[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][C:6]=1[C:7]([OH:9])=O)([CH3:3])[CH3:2].[CH2:15]([O:17][C:18]([C:20]1([NH2:31])[CH2:28][C:27]2[C:22](=[CH:23][CH:24]=[C:25]([O:29][CH3:30])[CH:26]=2)[CH2:21]1)=[O:19])[CH3:16].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:15]([O:17][C:18]([C:20]1([NH:31][C:7](=[O:9])[C:6]2[CH:10]=[CH:11][CH:12]=[C:13]([CH3:14])[C:5]=2[O:4][CH:1]([CH3:2])[CH3:3])[CH2:28][C:27]2[C:22](=[CH:23][CH:24]=[C:25]([O:29][CH3:30])[CH:26]=2)[CH2:21]1)=[O:19])[CH3:16]
Reactant: Cc1cccc(C(=O)O)c1OC(C)C
Reactant: CCOC(=O)C1(N)Cc2ccc(OC)cc2C1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)C1(NC(=O)c2cccc(C)c2OC(C)C)Cc2ccc(OC)cc2C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 89.8 %

Procedure:
To a solution of 2-isopropoxy-3-methyl-benzoic acid (300 mg, 1.54 mmol), 2-amino-5-methoxy-indan-2-carboxylic acid ethyl ester (435 mg, 1.85 mmol), HATU (878 g, 2.31 mmol) in anhydrous DMF (10 mL) is added DIPEA (382 μL, 2.31 mmol). The resulting solution is stirred at RT overnight. After the removal of DMF in vacuo, the residue is dissolved in EtOAc (100 mL) and washed with water (1×10 mL) and brine (2×10 mL). The organic layer is dried over anhydrous Na2SO4 and concentrated in vacuo. The residue is purified by flash column chromatography (115 g silica gel, gradient elution: 5%-40% EtOAc in heptane) to give a pure product (92) as a pale yellow oil (569 mg, 90%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8](Cl)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[NH2:12][CH2:13][CH:14]1[CH2:19][CH2:18][CH:17]([CH2:20][NH2:21])[CH2:16][CH2:15]1.C(N(C(C)C)CC)(C)C>ClCCl>[NH2:12][CH2:13][CH:14]1[CH2:19][CH2:18][CH:17]([CH2:20][NH:21][S:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)(=[O:10])=[O:9])[CH2:16][CH2:15]1
Reactant: O=S(=O)(Cl)c1ccc(F)cc1
Reactant: NCC1CCC(CN)CC1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: NCC1CCC(CNS(=O)(=O)c2ccc(F)cc2)CC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 99.1 %

Procedure:
A solution of 2.37 g of 4-fluorophenylsulfonyl chloride (12.2 mmol) in 30 ml of dichloromethane was added over 10 minutes to a stirred solution of 5.20 g of 1,4-bis-aminomethylcyclohexane (36.6 mmol) and 3.15 g of diisopropylethylamine (24.4 mmol) in 100 ml of dichloromethane at room temperature. The reaction mixture was stirred at room temperature for 16 hours, concentrated, and chromatographed on 200 g of silica packed with 5% MeOH (containing 2M NH3)-CHCl3, eluted with 5%, 7.5%, 10% (1 liter each) to give 3.63 g of the desired product.
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([S:11](Cl)(=[O:13])=[O:12])=[CH:7][CH:6]=1)(=[O:3])[CH3:2].C(=O)([O-])[O-].[Na+].[Na+].[NH2:21][CH2:22][CH:23]1[CH2:27][CH2:26][CH2:25][N:24]1[CH2:28][CH3:29]>C(Cl)(Cl)Cl>[C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([S:11]([NH:21][CH2:22][CH:23]2[CH2:27][CH2:26][CH2:25][N:24]2[CH2:28][CH3:29])(=[O:13])=[O:12])=[CH:7][CH:6]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)Nc1ccc(S(=O)(=O)Cl)cc1
Reactant: CCN1CCCC1CN
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: CCN1CCCC1CNS(=O)(=O)c1ccc(NC(C)=O)cc1
Temperature: 0 °C

Procedure:
4-Acetylaminobenzenesulphonyl chloride (7.3 g, 0.03 mol) was added portionwise to a well stirred mixture of aqueous sodium carbonate (21.2 g. in 250 ml of water) and 2-aminomethyl-1-ethylpyrrolidine (4.0 g. 0.03 mol) in chloroform (250 ml) at about 10°. The ice bath used for cooling was removed. After 2 hours the chloroform layer was separated, dried (MgSO4) and then evaporated under reduced pressure to give a gum, which slowly crystallised (11.6 g). Recrystallisation from cold ethanol, followed by recrystallisation from water gave the pure title compound m.p. 94°-96° C..
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:16]=[C:15]4[C:17]([C:28]([O:30]C)=[O:29])=[CH:18][N:19](COC(=O)C(C)(C)C)[C:14]4=[N:13][CH:12]=3)=[N:7][NH:8]2)=[CH:4][CH:3]=1.[OH-].[K+]>O1CCOCC1.O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:16]=[C:15]4[C:17]([C:28]([OH:30])=[O:29])=[CH:18][NH:19][C:14]4=[N:13][CH:12]=3)=[N:7][NH:8]2)=[CH:4][CH:3]=1
Reactant: COC(=O)c1cn(COC(=O)C(C)(C)C)c2ncc(-c3n[nH]c4cc(Cl)ccc34)nc12
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: O=C(O)c1c[nH]c2ncc(-c3n[nH]c4cc(Cl)ccc34)nc12
Yield: 124.2 %

Procedure:
A mixture of methyl 2-(6-chloro-1H-indazol-3-yl)-5-(pivaloyloxymethyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylate (202 mg, 0.457 mmol) and KOH (385 mg, 6.86 mmol) in 1,4-dioxane (10 mL) and water (5 mL) was heated to reflux for 3 hours. Reaction mixture was concentrated and the residue was adjusted to pH=5 with 1.0 M HCl aqueous. The precipitate was collected by filtration and dried to afford 2-(6-chloro-1H-indazol-3-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxylic acid (178 mg, crude) as a yellow solid. LCMS: (M+H)+=314.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11](=[O:12])[C:10]3[CH:13]=[CH:14][CH:15]=[C:16]([OH:17])[C:9]=3[CH2:8][CH2:7][C:6]=2[CH:18]=1.[O:19](S(C(F)(F)F)(=O)=O)[S:20]([C:23]([F:26])([F:25])[F:24])(=O)=[O:21]>N1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[C:11](=[O:12])[C:10]3[CH:13]=[CH:14][CH:15]=[C:16]([O:17][S:20]([C:23]([F:26])([F:25])[F:24])(=[O:21])=[O:19])[C:9]=3[CH2:8][CH2:7][C:6]=2[CH:18]=1
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Reactant: O=C1c2ccc(Cl)cc2CCc2c(O)cccc21
Solvent: c1ccncc1
Product: O=C1c2ccc(Cl)cc2CCc2c(OS(=O)(=O)C(F)(F)F)cccc21

Procedure:
For the preparation of the title compound, 0.517 g (0.0020 mol) of 8-chloro-1-hydroxy-10,11-dihydrodibenzo[a,d]cyclohepten-5-one and 0.846 g (0.0030 mol) of Tf2O in 5 ml of pyridine are reacted by method R. C16H10ClF3O4S (Mr=390.77); GC 11.9 min
Reaction SMILES: COC(C1SC([N:22]=[N+:23]=[N-:24])=C(C#N)C=1C1C=CC=CC=1C(C)(C)C)=O.[CH2:25]([O:27][C:28]([C:30]1[S:31][C:32](S(C)(=O)=O)=[C:33]([C:42]#[N:43])[C:34]=1[C:35]1[CH:40]=[CH:39][C:38]([I:41])=[CH:37][CH:36]=1)=[O:29])[CH3:26]>>[CH2:25]([O:27][C:28]([C:30]1[S:31][C:32]([N:22]=[N+:23]=[N-:24])=[C:33]([C:42]#[N:43])[C:34]=1[C:35]1[CH:40]=[CH:39][C:38]([I:41])=[CH:37][CH:36]=1)=[O:29])[CH3:26]
Reactant: CCOC(=O)c1sc(S(C)(=O)=O)c(C#N)c1-c1ccc(I)cc1
Reactant: COC(=O)c1sc(N=[N+]=[N-])c(C#N)c1-c1ccccc1C(C)(C)C
Product: CCOC(=O)c1sc(N=[N+]=[N-])c(C#N)c1-c1ccc(I)cc1

Procedure:
Using a method substantially in accordance with the method of example 5-azido-3-(tert-butyl-phenyl)-4-cyano-thiophene-2-carboxylic acid methyl ester starting with the compound 3-(4-iodophenyl)-4-cyano-5-methanesulfonyl-thiophene-2-carboxylic acid ethyl ester gives the title compound.
Reaction SMILES: C(O)(=O)C(O)=O.[NH:7]1[CH2:11][CH2:10][C@@H:9]([NH:12][C:13](=[O:22])[O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:8]1.Cl[C:24]1[C:33]2[C:28](=[CH:29][CH:30]=[C:31]([F:34])[CH:32]=2)[N:27]=[C:26]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=2[OH:41])[N:25]=1.C(N(CC)CC)C>C(Cl)Cl>[F:34][C:31]1[CH:32]=[C:33]2[C:28](=[CH:29][CH:30]=1)[N:27]=[C:26]([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[OH:41])[N:25]=[C:24]2[N:7]1[CH2:11][CH2:10][C@@H:9]([NH:12][C:13](=[O:22])[O:14][CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:8]1
Reactant: O=C(N[C@@H]1CCNC1)OCc1ccccc1
Reactant: Oc1ccccc1-c1nc(Cl)c2cc(F)ccc2n1
Agent: O=C(O)C(=O)O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(N[C@@H]1CCN(c2nc(-c3ccccc3O)nc3ccc(F)cc23)C1)OCc1ccccc1
Reaction time: 2 h
Yield: 83 %

Procedure:
A solution of (R)-benzyl pyrrolidin-3-ylcarbamate oxalate (1.35 g, 4.38 mmol) in CH2Cl2 (5 mL) was added dropwise to a solution of 2-(4-chloro-6-fluoroquinazolin-2-yl)phenol (1.0 g, 3.6 mmol) and triethylamine (1.22 mL, 8.76 mmol) in CH2Cl2 (10 mL). After stirring the mixture for 2 h, the reaction was quenched with H2O, the layers were separated, and the aqueous layer was extracted with CH2Cl2. The combined organic extracts were dried over MgSO4, filtered, and concentrated. The residue was purified via silica gel chromatography using 5-10% EtOAc in CH2Cl2 to give (R)-benzyl 1-(6-fluoro-2-(2-hydroxyphenyl)quinazolin-4-yl)pyrrolidin-3-ylcarbamate (1.37 g, 82%). 1H NMR (400 MHz, CDCl3) δ 8.39 (d, J=6.9 Hz, 1H), 7.80 (s, 1H), 7.68 (d, J=8.5 Hz, 1H), 7.46 (m, 1H), 7.37 (m, 6H), 7.01 (d, J=7.8 Hz, 1H), 6.90 (t, J=7.5 Hz, 1H), 5.17 (m, 2H), 4.51 (s, 1H), 4.25 (m, 1H), 4.10 (m, 2H), 3.91 (m, 1H), 2.37 (m, 1H), 2.12 (m, 1H). LC/MS: m/z 459.5 (M+H)+ at 2.80 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).
Reaction SMILES: [ClH:1].Cl.Cl.C([C:6]1[CH:7]=[CH:8][C:9]2[N:15]([CH2:16][C:17]3[N:18]=[CH:19][NH:20][CH:21]=3)[CH2:14][C@@H:13]([CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[NH:12][CH2:11][C:10]=2[CH:29]=1)#N.[CH:30](=O)[CH2:31][CH2:32][CH3:33].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>CC(O)=O.C(Cl)Cl>[ClH:1].[ClH:1].[ClH:1].[CH2:30]([N:12]1[CH2:11][C:10]2[CH:29]=[CH:6][CH:7]=[CH:8][C:9]=2[N:15]([CH2:16][C:17]2[N:18]=[CH:19][NH:20][CH:21]=2)[CH2:14][CH:13]1[CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:31][CH2:32][CH3:33]
Reactant: N#Cc1ccc2c(c1)CN[C@H](Cc1ccccc1)CN2Cc1c[nH]cn1
Reactant: CCCC=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: ClCCl
Solvent: CC(=O)O
Product: CCCCN1Cc2ccccc2N(Cc2c[nH]cn2)CC1Cc1ccccc1
Reaction time: 14 h
Yield: 354.3 %

Procedure:
A solution of Example 391 (0.23 g, 0.7 mmol) and butyraldehyde (1 g, 14 mmol) in 1:4 AcOH/CH2Cl2 (25 mL) was stirred at rt for 1 hr. NaBH(OAc)3 (3.0 g, 14 mmol) was added and stirring was continued for 14 hrs. The reaction was quenched with conc. NH4OH and diluted with 10% iPrOH in CH2Cl2 (50 mL). The organic phase was washed with 1 N NaOH (2×20 mL), dried over Na2SO4 and evaporated to give a yellow solid (0.4 g) which was purified by reverse phase preparative HPLC (gradient of aqueous methanol with 0.1% TFA) and converted to the HCl salt by lyophilizing with 1N HCl to give Example 392 as a yellow solid (45 mg, 12%).
Reaction SMILES: O1CCCC1.[NH:6]1[CH:10]=[CH:9][N:8]=[C:7]1[CH2:11][CH:12]([CH2:43][C:44]1[NH:45][CH:46]=[CH:47][N:48]=1)[CH2:13][NH:14][C:15]([C:17]1[CH:42]=[CH:41][C:20]([CH2:21][N:22]2[CH:26]([C:27]([O:29]CC)=[O:28])[CH2:25][C:24]3([CH2:36][CH2:35][N:34]([CH2:37][CH:38]([CH3:40])[CH3:39])[CH2:33][CH2:32]3)[CH2:23]2)=[CH:19][CH:18]=1)=[O:16].[OH-].[Na+].Cl>CO>[NH:6]1[CH:10]=[CH:9][N:8]=[C:7]1[CH2:11][CH:12]([CH2:43][C:44]1[NH:45][CH:46]=[CH:47][N:48]=1)[CH2:13][NH:14][C:15]([C:17]1[CH:18]=[CH:19][C:20]([CH2:21][N:22]2[CH:26]([C:27]([OH:29])=[O:28])[CH2:25][C:24]3([CH2:32][CH2:33][N:34]([CH2:37][CH:38]([CH3:39])[CH3:40])[CH2:35][CH2:36]3)[CH2:23]2)=[CH:41][CH:42]=1)=[O:16]
Reactant: CCOC(=O)C1CC2(CCN(CC(C)C)CC2)CN1Cc1ccc(C(=O)NCC(Cc2ncc[nH]2)Cc2ncc[nH]2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: CC(C)CN1CCC2(CC1)CC(C(=O)O)N(Cc1ccc(C(=O)NCC(Cc3ncc[nH]3)Cc3ncc[nH]3)cc1)C2
Temperature: 50 °C
Reaction time: 3 h
Yield: 72.1 %

Procedure:
To a tetrahydrofuran (2 mL)-methanol (2 mL) solution of the compound (51 mg) produced in Example 80(3), an aqueous 2N sodium hydroxide solution (0.5 mL) was added. The reaction solution was stirred at 50° C. for 3 hours. To the reaction solution, 1N hydrochloric acid was added so as to adjust the pH to about 5. The reaction solution was concentrated under reduced pressure. The residue was washed with ethanol. An insoluble salt was removed by filtration, and then the filtrate was concentrated. The residue was purified by silica gel chromatography (dichloromethane:methanol: 28% aqueous ammonia=8:2:0.5) to obtain the title compound (35 mg) having the following physical properties.
Reaction SMILES: C(OC(=O)[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[S:15][CH:16]=[CH:17][CH:18]=2)=[CH:10][C:9]=1[NH:19][C:20]([C:22]1[S:26][C:25]2[CH:27]=[C:28]([CH:31]([C:33](=[O:35])[NH2:34])[F:32])[CH:29]=[CH:30][C:24]=2[CH:23]=1)=[O:21])(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[S:15][CH:16]=[CH:17][CH:18]=2)=[CH:10][C:9]=1[NH:19][C:20]([C:22]1[S:26][C:25]2[CH:27]=[C:28]([CH:31]([C:33](=[O:35])[NH2:34])[F:32])[CH:29]=[CH:30][C:24]=2[CH:23]=1)=[O:21]
Reactant: CC(C)(C)OC(=O)Nc1ccc(-c2cccs2)cc1NC(=O)c1cc2ccc(C(F)C(N)=O)cc2s1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: NC(=O)C(F)c1ccc2cc(C(=O)Nc3cc(-c4cccs4)ccc3N)sc2c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of (2-{[6-(carbamoyl-fluoro-methyl)-benzo[b]thiophene-2-carbonyl]-amino}-4-thiophen-2-yl-phenyl)-carbamic acid tert-butyl ester (163 mg, 0.31 mmol)) in methylene chloride (2 mL) was added trifluoroacetic acid (1 mL) and the solution was stirred at ambient temperature for 16 hours. The reaction was evaporated to dryness. The residue was washed with sat. NaHCO3 and MeOH, and the solid was filtered. 1H NMR (DMSO-d6) δ 10.03 (br s, 1H), 8.33 (s, 1H), 8.11 (s, 1H), 8.02 (d, J=8.2 Hz, 1H), 7.93 (s, 1H), 7.62 (br d, J=2.4 Hz, 1H), 7.51 (d, J=8.2 Hz, 1H), 7.45 (d, J=1.8 Hz, 1H), 7.33 (dd, J=5.0, 1.8 Hz, 1H), 7.29 (dd, J=8.2, 1.8 Hz, 1H), 7.23 (dd, J=3.5, 1.8 Hz, 1H), 7.02 (dd, J=5.2, 3.5 Hz, 1H), 6.79 (d, J=8.2 Hz, 1H), 5.93 (d, J=45.7 Hz, 1H), 5.24 (s, 2H). cal'd 427 (MH+), exp 427 (MH+).
Reaction SMILES: [F:1][CH:2]([F:10])[C:3]1[N:4]=[C:5]([CH2:8][OH:9])[S:6][CH:7]=1.Br[C:12]1[CH:17]=[CH:16][N:15]([C:18]2[CH:19]=[CH:20][C:21]3[N:25]=[C:24]([CH:26]4[CH2:28][CH2:27]4)[N:23]([CH3:29])[C:22]=3[CH:30]=2)[C:14](=[O:31])[CH:13]=1.[H-].[Na+].CC(N(C)C)=O>O>[CH:26]1([C:24]2[N:23]([CH3:29])[C:22]3[CH:30]=[C:18]([N:15]4[CH:16]=[CH:17][C:12]([O:9][CH2:8][C:5]5[S:6][CH:7]=[C:3]([CH:2]([F:10])[F:1])[N:4]=5)=[CH:13][C:14]4=[O:31])[CH:19]=[CH:20][C:21]=3[N:25]=2)[CH2:27][CH2:28]1
Reactant: Cn1c(C2CC2)nc2ccc(-n3ccc(Br)cc3=O)cc21
Reactant: OCc1nc(C(F)F)cs1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)N(C)C
Product: Cn1c(C2CC2)nc2ccc(-n3ccc(OCc4nc(C(F)F)cs4)cc3=O)cc21
Temperature: 120 °C
Yield: 19.7 %

Procedure:
A mixture of (4-(difluoromethyl)-1,3-thiazol-2-yl)methanol (50 mg), 4-bromo-1-(2-cyclopropyl-1-methyl-1H-benzo[d]imidazol-6-yl)pyridin-2(1H)-one (69.5 mg), NaH (60% in oil, 12.1 mg) and DMA (1 ml) was heated at 120° C. under microwave irradiation for 2 h. The mixture was poured into water and extracted with EtOAc. The extract was washed with brine, dried over MgSO4, concentrated in vacuo, and purified by NH silica gel column chromatography (hexane/EtOAc) to give the title compound (17 mg) as a white solid.
Reaction SMILES: C([NH:11][C@@H:12]([CH2:16][C:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[NH:19][C:18]=1[C@H:26]1[O:55][C@H:54]([CH2:56][O:57]CC2C=CC=CC=2)[C@@H:45]([O:46]CC2C=CC=CC=2)[C@H:36]([O:37]CC2C=CC=CC=2)[C@@H:27]1[O:28]CC1C=CC=CC=1)[C:13]([OH:15])=[O:14])(OCC1C=CC=CC=1)=O.[H][H]>C(O)C.[OH-].[Pd+2].[OH-].[C]>[NH2:11][C@@H:12]([CH2:16][C:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[NH:19][C:18]=1[C@H:26]1[O:55][C@H:54]([CH2:56][OH:57])[C@@H:45]([OH:46])[C@H:36]([OH:37])[C@@H:27]1[OH:28])[C:13]([OH:15])=[O:14]
Reactant: O=C(N[C@@H](Cc1c([C@H]2O[C@H](COCc3ccccc3)[C@@H](OCc3ccccc3)[C@H](OCc3ccccc3)[C@@H]2OCc2ccccc2)[nH]c2ccccc12)C(=O)O)OCc1ccccc1
Reactant: [H][H]
Agent: [Pd+2]
Agent: [OH-]
Solvent: CCO
Product: N[C@@H](Cc1c([C@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@@H]2O)[nH]c2ccccc12)C(=O)O
Yield: 59.6 %

Procedure:
To a solution of (2S*)-2-[N-(carbobenzyloxy)amino]-3-[2-(2,3,4,6-tetra-O-benzyl-α-D-mannopyranosyl)indole-3-yl]propionic acid [compound (XII-2) wherein R1 to R4 are benzyl and Ar is phenyl](90.5 mg (0.11 mmol)) in ethanol (25 ml) was added 20% palladium hydroxide-carbon catalyst (75 mg) and the mixture was stirred at about 60° C. for about 11 hours under atmospheric pressure in the presence of hydrogen. The reacted solution was filtrated on Celite and the filtrate was concentrated. The residue was fractionated by high performance liquid chromatography [column: YMC-Pack ODS-AM SH-365-10AM, 500×30 mm, S-10, 120Å; temperature: room temperature; migrating layer: 5% acetonitrile-water; flow rate: 40 ml/min.; detection: 278 nm (UV)] and then freeze-dried to give 24 mg (yield 62%) of (2S*)-2-amino-3-[2-(α-D-mannopyranosyl)indole-3-yl]propionic acid [compound (XIII-2)].
Reaction SMILES: [C:1]([N:4]1[C:12]2[C:11]([Cl:13])=[CH:10][CH:9]=[C:8]3[C:14](=[O:20])[CH:15]([N:17]=[N+]=[N-])[CH2:16][C:6]([C:7]=23)=[CH:5]1)(=[O:3])[CH3:2].Cl>C(OC(=O)C)C.C(O)C>[ClH:13].[C:1]([N:4]1[C:12]2[C:11]([Cl:13])=[CH:10][CH:9]=[C:8]3[C:14](=[O:20])[CH:15]([NH2:17])[CH2:16][C:6]([C:7]=23)=[CH:5]1)(=[O:3])[CH3:2]
Reactant: CC(=O)n1cc2c3c(ccc(Cl)c31)C(=O)C(N=[N+]=[N-])C2
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CCO
Product: CC(=O)n1cc2c3c(ccc(Cl)c31)C(=O)C(N)C2

Procedure:
Into a stirred solution of 1-acetyl-4-azido-8-chloro-3,4-dihydrobenz[cd]-indol-5(1H)-one (3.5 g., 0.012 mole) in ethylacetate-ethanol (1:1) (200 ml.), containing 4 gm. of 6 N hydrochloric acid and 0.5 g. of 10% palladium on carbon catalyst, is bubbled a stream of hydrogen gas. After 2.5 hours the product which has separated is recovered by filtration. The yield of crude product which contains some of the catalyst is 2.6 g. (72%).
Reaction SMILES: [OH:1][CH2:2][CH:3]([CH2:5][OH:6])[OH:4].[CH3:7][C:8]1[CH:12]=[C:11]([CH3:13])[NH:10][C:9]=1/[CH:14]=[C:15]1\[C:16](=[O:27])[N:17]([C:24](Cl)=[O:25])[C:18]2[C:23]\1=[CH:22][CH:21]=[CH:20][CH:19]=2>N1C=CC=CC=1.C1COCC1>[OH:4][CH:3]([CH2:5][OH:6])[CH2:2][O:1][C:24]([N:17]1[C:18]2[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=2)/[C:15](=[CH:14]/[C:9]2[NH:10][C:11]([CH3:13])=[CH:12][C:8]=2[CH3:7])/[C:16]1=[O:27])=[O:25]
Reactant: OCC(O)CO
Reactant: Cc1cc(C)c(/C=C2\C(=O)N(C(=O)Cl)c3ccccc32)[nH]1
Solvent: c1ccncc1
Solvent: C1CCOC1
Product: Cc1cc(C)c(/C=C2\C(=O)N(C(=O)OCC(O)CO)c3ccccc32)[nH]1
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
To the solution of glycerol (460 mg, 2.5 mmol) in 1.0 mL of pyridine and 2.0 mL of THF was added a suspention of 3-[1-(3,5-dimethyl-1H-pyrrol-2-yl)-meth-(Z)-ylidene]-2-oxo-2,3-dihydro-indole-1-carbonyl chloride in 2.0 mL of THF at 0° C. The reaction mixture was gradually warmed to room temperature, stirred for 2.5 h, and concentrated. The residue was triturated with ethyl acetate and filtered. The solid was then washed with ethyl acetate, water, ether, and dried to yield 87 mg of 3-[1-(3,5-dimethyl-1H-pyrrol-2-yl)-meth-(Z)-ylidene]-2-oxo-2,3-dihydro-indole-1-carboxylic acid 2,3-dihydroxy-propyl ester. The combined filtrate was concentrated and partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated to give 120 mg of crude product which was suspended in water, filtered, and washed with small amount of ethyl acetate to afford another 67 mg of 3-[1-(3,5-dimethyl-1H-pyrrol-2-yl)-meth-(Z)-ylidene]-2-oxo-2,3-dihydro-indole-1-carboxylic acid 2,3dihydroxy-propyl ester. The combined yield is 83%. 1H NMR (400 MHz, CDCl3) δ 12.51 (s, 1H, NH-1′), 7.90-7.92 (m, 1H), 7.45-7.48 (m, 1H), 7.37 (s, 1H, H-vinyl), 7.18-7.24 (m, 2H), 6.04 (d, J=1.96 Hz, 1H, H-4′), 4.68 (dd, J=3.13, 11.24 Hz, 1H, OCH2CH(OH)CH2OH), 4.45 (dd, J=4.89, 11.24 Hz, 1H, OCH2CH(OH)CH2OH), 4.09 (m, br, 1H, OCH2CH(OH)CH2OH), 3.86-3.99 (m, 2H, OCH2CH(OH)CH2OH), 3.60 (d, J=6.65 Hz, 1H, OCH2CH(OH)CH2OH), 3.45 (dd, J=5.52, 7.82 Hz, 1H, OCH2CH(OH)CH2OH), 2.41 (s, 3H, CH3), and 2.32 (s, 3H, CH3). MS m/z (relative intensity, %) 357 (100, [M+1]+.).