Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[S:10][C:9]2[C:4](=[N:5][CH:6]=[CH:7][C:8]=2[O:11][C:12]2[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][C:13]=2[F:21])[CH:3]=1.CC1(C)C(C)(C)OB([C:30]2[CH:35]=[CH:34][C:33]([S:36]([CH3:39])(=[O:38])=[O:37])=[CH:32][CH:31]=2)O1.[F-].[Cs+].C([O-])(O)=O.[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:21][C:13]1[CH:14]=[C:15]([N+:18]([O-:20])=[O:19])[CH:16]=[CH:17][C:12]=1[O:11][C:8]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:3]=[C:2]([C:30]3[CH:35]=[CH:34][C:33]([S:36]([CH3:39])(=[O:38])=[O:37])=[CH:32][CH:31]=3)[S:10][C:9]=12
Reactant: CC1(C)OB(c2ccc(S(C)(=O)=O)cc2)OC1(C)C
Reactant: O=[N+]([O-])c1ccc(Oc2ccnc3cc(Br)sc23)c(F)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])O
Agent: [Cs+]
Solvent: COCCOC
Solvent: O
Product: CS(=O)(=O)c1ccc(-c2cc3nccc(Oc4ccc([N+](=O)[O-])cc4F)c3s2)cc1
Yield: 16.8 %

Procedure:
To a solution of 42 (461 mg, 1.3 mmol, scheme 8) in DME (4 mL) was added 4,4,5,5-tetramethyl-2-(4-(methylsulfonyl)phenyl)-1,3,2-dioxaborolane (500 mg, 2.5 mmol), CsF (391 mg, 3.8 mmol), Pd(PPh3)4 (72 mg, 63 μmol) and NaHCO3 (315 mg, 3.8 mmol) pre-dissolved in H2O (1 ml). The reaction mixture was purged with nitrogen and refluxed for 2 hours. The DME was removed under reduced pressure and the aqueous layer was extracted with EtOAc. The extract was dried over sodium sulphate, filtered and evaporated to form a residue which was purified by column chromatography (eluent EtOAc/hexane, 1:1) to afford the title compound 48 (97 mg, 18% yield) as a white solid. 1HNMR (DMSO) δ (ppm): 8.63 (d, J=1.2 Hz, 1H), 8.49 (d-d, J=2.7 Hz, 1H), 8.33 (s, 1H), 8.22-8.19 (m, 2H), 8.16 (s, 2H), 8.02 (d, J=8.6 Hz, 2H), 7.75 (t, J=8.0 Hz, 1H), 7.77-7.58 (m, 2H), 7.58-7.50 (m, 2H), 6.97 (d, J=5.5 Hz, 1H), 3.33 (s, 3H), MS (m/z): 444.8 (M+H).
Reaction SMILES: [Br-].[CH3:2][C:3]1([CH3:33])[S:7][C:6]2[CH:8]=[CH:9][C:10]([CH:12]([P+](C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[CH3:13])=[CH:11][C:5]=2[S:4]1.C([Li])CCC.[O:39]1[CH2:44][CH2:43][N:42]([CH2:45][CH2:46][O:47][C:48]2[CH:55]=[CH:54][C:51]([CH:52]=O)=[CH:50][CH:49]=2)[CH2:41][CH2:40]1>O1CCCC1.CCCCCC>[CH3:33][C:3]1([CH3:2])[S:7][C:6]2[CH:8]=[CH:9][C:10](/[C:12](/[CH3:13])=[CH:52]/[C:51]3[CH:50]=[CH:49][C:48]([O:47][CH2:46][CH2:45][N:42]4[CH2:41][CH2:40][O:39][CH2:44][CH2:43]4)=[CH:55][CH:54]=3)=[CH:11][C:5]=2[S:4]1
Reactant: O=Cc1ccc(OCCN2CCOCC2)cc1
Reactant: CC(c1ccc2c(c1)SC(C)(C)S2)[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: C/C(=C\c1ccc(OCCN2CCOCC2)cc1)c1ccc2c(c1)SC(C)(C)S2
Temperature: 20 °C
Reaction time: 0.67 h
Yield: 35.2 %

Procedure:
6.6 g of [1-(2,2-dimethyl-1,3-benzodithiol-5-yl)ethyl]triphenylphosphonium bromide were dissolved in 40 ml of tetrahydrofuran and treated slowly at 0° C. with 9 ml of a 1.5 molar solution of n-butyllithium in hexane. After 40 minutes, 3.5 g of 4-(2-morpholinoethoxy)benzaldehyde in 10 ml of tetrahydrofuran were added dropwise to the dark red solution and the mixture was stirred at 20° C. for 16 hours. The mixture was then poured on to ice and extracted with ethyl acetate. The combined extracts were washed with water, dried and evaporated. After chromatography (silica gel, eluting agent ethyl acetate) and crystallization from ether/hexane, there were obtained 1.8 g of 4-[2-[p-[(E)-2-(2,2-dimethyl-1,3-benzodithiol-5-yl)propenyl]phenoxy]ethyl]morpholine in the form of colorless crystals, melting point 90°-91° C.
Reaction SMILES: NC1C(=O)N2C(C(O)=O)=C(CO)CS[C@H]12.C(=O)([O-])[O-].[Na+].[Na+].Cl.[C:23]([O:27][C:28]([CH2:30][O:31][N:32]=[C:33]([C:51]1[N:52]=[C:53]([NH:56][CH:57]=[O:58])[S:54][CH:55]=1)[C:34]([NH:36][CH:37]1[C:49](=[O:50])[N:39]2[C:40]([C:46]([OH:48])=[O:47])=[C:41]([CH2:44][OH:45])[CH2:42][S:43][C@H:38]12)=[O:35])=[O:29])([CH3:26])([CH3:25])[CH3:24].[C:59]1([C:65]([C:68]2[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=2)=[N+]=[N-])[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1>C(=O)(O)[O-].[Na+].O.CC(C)=O.C(OCC)(=O)C>[C:23]([O:27][C:28]([CH2:30][O:31][N:32]=[C:33]([C:51]1[N:52]=[C:53]([NH:56][CH:57]=[O:58])[S:54][CH:55]=1)[C:34]([NH:36][CH:37]1[C:49](=[O:50])[N:39]2[C:40]([C:46]([O:48][CH:65]([C:59]3[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=3)[C:68]3[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=3)=[O:47])=[C:41]([CH2:44][OH:45])[CH2:42][S:43][C@H:38]12)=[O:35])=[O:29])([CH3:26])([CH3:24])[CH3:25]
Reactant: [N-]=[N+]=C(c1ccccc1)c1ccccc1
Reactant: CC(C)(C)OC(=O)CON=C(C(=O)NC1C(=O)N2C(C(=O)O)=C(CO)CS[C@H]12)c1csc(NC=O)n1
Agent: Cl
Agent: NC1C(=O)N2C(C(=O)O)=C(CO)CS[C@H]12
Agent: O=C([O-])O
Solvent: CCOC(C)=O
Solvent: CC(C)=O
Solvent: O
Product: CC(C)(C)OC(=O)CON=C(C(=O)NC1C(=O)N2C(C(=O)OC(c3ccccc3)c3ccccc3)=C(CO)CS[C@H]12)c1csc(NC=O)n1

Procedure:
On the other hand, 7-amino-3-hydroxymethyl-3-cephem-4-carboxylic acid (11.5 g) was dissolved in a solution of sodium bicarbonate (8.4 g) in water (50 ml) and acetone (50 ml). To this solution was added dropwise the activated acid solution obtained above at 3° to 8° C. while keeping the pH value of the mixture to 7-8 with 20% aqueous sodium carbonate, and the mixture was stirred at the same temperature for an hour. The reaction mixture was adjusted to pH 6.0 with 10% hydrochloric acid and then washed with ethyl acetate to give an aqueous solution containing 7-[2-tertbutoxycarbonylmethoxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-hydroxymethyl-3-cephem-4-carboxylic acid (syn isomer). To this aqueous solution was added a solution of diphenyldiazomethane in ethyl acetate (1 mmol/ml)(100 ml), and the mixture was acidified to pH 2.5 with 10% hydrochloric acid. After stirring at ambient temperature for 2 hours, the solution was extracted with a mixture of ethyl acetate and tetrahydrofuran (1:1). The extract was washed with a saturated aqueous sodium bicarbonate and an aqueous sodium chloride, followed by drying over magnesium sulfate. The solution was evaporated and the residue was pulverized with diethyl ether to give benzhydryl 7-[2-tert-butoxycarbonylmethoxyimino-2-(2-formamidothiazol-4-yl)acetamido]-3-hydroxymethyl-3-cephem-4-carboxylate (syn isomer)(18.5 g).
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[C:11]2[CH:12]=[CH:13][C:14]([C:16](=[N:19]O)[CH2:17][CH3:18])=[CH:15][C:10]=2[N:9]=[CH:8]1>C1COCC1.[Ni]>[O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[N:7]1[C:11]2[CH:12]=[CH:13][C:14]([CH:16]([NH2:19])[CH2:17][CH3:18])=[CH:15][C:10]=2[N:9]=[CH:8]1
Reactant: CCC(=NO)c1ccc2c(c1)ncn2C1CCCCO1
Agent: [Ni]
Solvent: C1CCOC1
Product: CCC(N)c1ccc2c(c1)ncn2C1CCCCO1
Temperature: 25 °C
Reaction time: 8 h
Yield: 35.1 %

Procedure:
To a solution of 172 (30 mg, 0.11 mmol) in THF (3 mL) was added Raney-Ni (50 mg) and the mixture was stirred at RT overnight, filtered and concentrated in vacuo. Purification by HPLC afforded 10 mg (35%) of 1-(1-tetrahydropyran-2-ylbenzimidazol-5-yl)propan-1-amine (174) as a colourless oil: 1H NMR (400 MHz, CDCl3): δ 7.98 (m, 1H), 7.64 (m, 1H), 7.40 (m, 1H), 7.14-7.36 (m, 1H), 5.40-5.45 (m, 1H), 4.06 (m, 1H), 3.85 (m, 1H), 3.70 (m, 1H), 2.02-2.10 (m, 3H), 1.62-1.72 (m, 8H), 0.77-0.84 (m, 3H); MS (ESI+) m/z=260 [M+1]+.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][C:6]([OH:10])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[OH-].[K+].[CH3:13][N:14]1[CH2:19][CH2:18][C:17](=O)[CH2:16][CH2:15]1>CO>[CH3:13][N:14]1[CH2:15][CH:16]=[C:17]([C:3]2[C:4]3[C:9](=[CH:8][CH:7]=[C:6]([OH:10])[CH:5]=3)[NH:1][CH:2]=2)[CH2:18][CH2:19]1
Reactant: Oc1ccc2[nH]ccc2c1
Reactant: CN1CCC(=O)CC1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: CN1CC=C(c2c[nH]c3ccc(O)cc23)CC1
Temperature: 70 °C
Yield: 66.5 %

Procedure:
To a solution of 1H-indol-5-ol (18.60 g, 0.14 mol) in methanol (250 ml), stirring at room temperature under nitrogen, was slowly added potassium hydroxide (31.4 g, 0.56 mol) in methanol (100 mL). 1-methyl-4-piperidone (29.0 mL, 0.24 mol) was added dropwise to the black solution. The reaction mixture was heated at 70° C. for 8 hours, cooled to room temperature, concentrated in vacuo. The resulting residue was directly purified on silica gel. Elution with a 9:1 mixture of dichloromethane and 7 N ammonia in methanol provided 21.25 g (62%) of the title compound as a tan solid: mp=182-185° C.; 1H NMR (400 MHz, dmso-d6): 10.78 (br s, 1H), 8.64 (s, 1H), 7.22 (d, 1H, J=2.4 Hz), 7.13 (d, 1H, J=8.8 Hz), 7.10 (d, 1H, J=1.6 Hz), 6.59 (dd, 1H, J=8.8, 1.2 Hz), 5.94 (br s, 1H), 3.02-2.98 (m, 2H), 2.52 (br t, 2H, J=5.6 Hz), 2.48-2.42 (m, 2H), 2.24 (s, 3H); MS (APCI): m/e 229.1 (M+1).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][CH:11]=1)[NH:8][CH2:7][CH2:6][CH:5]2[O:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=1.[CH3:20][N:21]1[CH2:26][CH2:25][N:24]([C:27]2[CH:32]=[C:31](B3OC(C)(C)C(C)(C)O3)[CH:30]=[CH:29][N:28]=2)[CH2:23][CH2:22]1>C(OCC)(=O)C.CCCCCC>[Cl:19][C:15]1[CH:14]=[C:13]([CH:18]=[CH:17][CH:16]=1)[O:12][CH:5]1[C:4]2[C:9](=[N:10][CH:11]=[C:2]([C:31]3[CH:30]=[CH:29][N:28]=[C:27]([N:24]4[CH2:23][CH2:22][N:21]([CH3:20])[CH2:26][CH2:25]4)[CH:32]=3)[CH:3]=2)[NH:8][CH2:7][CH2:6]1
Reactant: CN1CCN(c2cc(B3OC(C)(C)C(C)(C)O3)ccn2)CC1
Reactant: Clc1cccc(OC2CCNc3ncc(Br)cc32)c1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: CN1CCN(c2cc(-c3cnc4c(c3)C(Oc3cccc(Cl)c3)CCN4)ccn2)CC1
Yield: 36 %

Procedure:
6-Bromo-4-(3-chlorophenoxy)-1,2,3,4-tetrahydro-[1,8]naphthyridine (20 mg) was reacted with 1-methyl-4-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyridin-2-yl]piperazine (25 mg) as in General Procedure 13. Silica gel chromatography using a gradient of 0-100% ethyl acetate/hexane as the eluting solvent gave the title compound as a white foam (36% yield). LCMS: m/z=436.06 (M+H+), 1H-NMR (CDCl3, 400 MHz) δ 2.0-2.11 (m, 1H), 2.24-2.40 (m, 1H), 2.35 (s, 3H), 2.54 (t, J=4.9 Hz, 4H), 3.4-3.51 (m, 1H), 3.57-3.68 (m, 5H), 5.27 (bs, 1H), 5.38 (t, J=3.4 Hz, 1H), 6.64 (s, 1H), 6.73 (dd, J=1.0 and 5.2 Hz, 1H), 6.90 (dd, J=2.2 and 8.3 Hz, 1H), 6.95-7.03 (m, 1H), 7.04-7.08 (m, 1H), 7.22-7.28 (m, 1H), 7.57 (d, J=1.9 Hz, 1H), 8.17 (d, J=5.2 Hz, 1H), 8.31 (d, J=2.2 Hz).
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:20])[C@@H:10]([CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[NH2:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:28]([O:32][C:33]([NH:35][C:36]([CH3:42])([CH3:41])[CH2:37][C:38](O)=[O:39])=[O:34])([CH3:31])([CH3:30])[CH3:29].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(Cl)Cl>[CH2:1]([O:8][C:9](=[O:20])[C@H:10]([NH:11][C:38](=[O:39])[CH2:37][C:36]([NH:35][C:33]([O:32][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:34])([CH3:42])[CH3:41])[CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(CC(=O)O)NC(=O)OC(C)(C)C
Reactant: N[C@H](CCc1ccccc1)C(=O)OCc1ccccc1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(CC(=O)N[C@H](CCc1ccccc1)C(=O)OCc1ccccc1)NC(=O)OC(C)(C)C

Procedure:
D-Homophenylalanine benzyl ester (725 mg; 3.23 mmol) whose preparation was described in Example 7 Step B, triethylamine (750 ml; 5,38 mmol) and 3-t-butoxycarbonylamino-3-methylbutanoic acid (585 mg; 2.69 mmol) were dissolved in dry methylene chloride (10 ml) and BOP (1.19 g, 2.69 mmol) was added with stirring in small batches to give a slightly cloudy solution. The reaction mixture was stirred at room temperature for 24 h then quenched by adding saturated brine (10 ml). The two phase system was extracted with methylene chloride (2×25 ml) and the combined methylene chloride extracts dried over magnesium sulfate powder, filtered and evaporated on a rotary evaporator under reduced pressure to give a cloudy, colorless oil. This material was taken up in the minimum volume of methylene chloride and chromatographed on silica gel using an eluant composed of ethyl acetate and hexanes in the ratio 1:1 v/v. The product was isolated after evaporation of the volatiles as a clear oil. The yield was 710 mg (88.5%). FAB-MS: -calculated for C27H36N2 O5 468.3; found 469.6 (M+1).
Reaction SMILES: Cl.Cl.[N:3]12[CH2:10][CH2:9][C:6]([CH2:11][NH2:12])([CH2:7][CH2:8]1)[CH2:5][CH2:4]2.C[O-].[Na+].C(O)(=O)C.C([BH3-])#N.[Na+].O=[CH:25][CH2:26][N:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][C:34]=2[C:36]([O:38][CH3:39])=[O:37])[CH:29]=[N:28]1>CO>[N:3]12[CH2:10][CH2:9][C:6]([CH2:11][NH:12][CH2:25][CH2:26][N:27]3[C:35]4[C:30](=[CH:31][CH:32]=[CH:33][C:34]=4[C:36]([O:38][CH3:39])=[O:37])[CH:29]=[N:28]3)([CH2:7][CH2:8]1)[CH2:5][CH2:4]2
Reactant: NCC12CCN(CC1)CC2
Reactant: COC(=O)c1cccc2cnn(CC=O)c12
Agent: C[O-]
Agent: Cl
Agent: [BH3-]C#N
Solvent: CC(=O)O
Solvent: CO
Product: COC(=O)c1cccc2cnn(CCNCC34CCN(CC3)CC4)c12
Temperature: 25 °C
Reaction time: 1 h
Yield: 39.1 %

Procedure:
To a stirred solution of quinuclidin-4-ylmethanamine dihydrochloride (894 mg, 4.2 mmol) in methanol (12 mL) at room temperature was added sodium methoxide (25 wt % in MeOH, 1.8 mL, 8.4 mmol) dropwise. The reaction was stirred at room temperature for 1 h and then glacial acetic acid (0.6 mL, 9.7 mmol) was added to neutralize the basicity of the mixture. Sodium cyanoborohydride (528 mg, 8.4 mmol) was added, followed by a solution of methyl 1-(2-oxoethyl)-1H-indazole-7-carboxylate (920 mg, 4.2 mmol) from Step E above in methanol (10 mL). The mixture was stirred at room temperature until the reaction was complete by TLC (1-2 h). The reaction mixture was concentrated, absorbed onto silica gel, and purified by column chromatography (80:18:2 methylene chloride/methanol/concentrated ammonium hydroxide) to afford methyl 1-(2-(quinuclidin-4-ylmethylamino)ethyl)-1H-indazole-7-carboxylate as a yellow oil (563 mg, 39%): 1H NMR (300 MHz, CD3OD) δ 8.26 (s, 1H), 8.09-8.03 (m, 2H), 7.27 (t, J=7.2 Hz, 1H), 4.95 (t, J=5.7 Hz, 2H), 4.01 (s, 3H), 3.50-3.44 (m, 2H), 3.39 (t, J=7.8 Hz, 6H), 2.93 (s, 2H), 1.85 (t, J=8.1 Hz, 6H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][C:10]([OH:12])=O)[CH:5]=[CH:6][CH:7]=1.[CH:13]([NH:16][NH:17][C:18](=[O:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)([CH3:15])[CH3:14].C(N(CC)CC)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([CH2:8][CH2:9][C:10]([N:16]([CH:13]([CH3:15])[CH3:14])[NH:17][C:18](=[O:25])[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:12])[CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)CCc1cccc(Br)c1
Reactant: CC(C)NNC(=O)c1ccccc1
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: CC(C)N(NC(=O)c1ccccc1)C(=O)CCc1cccc(Br)c1
Yield: 67.2 %

Procedure:
A solution of (3-(3-bromophenyl)propionic acid (257 mg, 1.12 mmoles) and benzoic acid N′-isopropyl-hydrazide (200 mg, 1.12 mmoles) in DMF (6 mL) was treated with triethylamine (0.47 mL, 3.36 mmoles), HOBT (182 mg, 1.34 mmoles) and EDCI (2.58 mg, 1.34 mmoles) at room temperature for 18 h. The reaction mixture was partitioned between water and dichloromethane. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated. The crude was absorbed on silica and purified on a silica gel column with a 20-40% ethyl acetate/hexanes gradient to afford the product as a solid (293 mg, 67%).
Reaction SMILES: [CH3:1][C:2]1[C:7]([NH:8]C(=O)CCC)=[CH:6][N:5]=[C:4]2[N:14]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[S:33]([NH2:36])(=[O:35])=[O:34])=[CH:23][CH:22]=3)[C:15]([CH2:17][CH2:18][CH3:19])=[N:16][C:3]=12>CO.Cl>[NH2:8][C:7]1[C:2]([CH3:1])=[C:3]2[N:16]=[C:15]([CH2:17][CH2:18][CH3:19])[N:14]([CH2:20][C:21]3[CH:22]=[CH:23][C:24]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[S:33]([NH2:36])(=[O:35])=[O:34])=[CH:25][CH:26]=3)[C:4]2=[N:5][CH:6]=1
Reactant: CCCC(=O)Nc1cnc2c(nc(CCC)n2Cc2ccc(-c3ccccc3S(N)(=O)=O)cc2)c1C
Agent: Cl
Solvent: CO
Product: CCCc1nc2c(C)c(N)cnc2n1Cc1ccc(-c2ccccc2S(N)(=O)=O)cc1
Temperature: 50 °C

Procedure:
A mixture of 7-methyl-2-propyl-3-[2'-(aminosulfonyl)[1,1']biphenyl-4-yl]methyl-6-[(1-oxobutyl)amino]-3H-imidazo[4,5-b]pyridine (180 mg) in 10 mL of MeOH and 1 mL of conc aqueous HCl was heated to 50° C. for 30 h. The MeOH was removed in vacuo and 100 mL of CH2Cl2 was added. The mixture was washed with saturated aqueous NaHC03 (2×30 mL), dried (Na2SO4), and concentrated to give the title compound as a foam.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8]([C:13]([O:15]CC)=[O:14])=[C:7]2[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)([O-])=O.[F:24][C:25]([F:38])([F:37])[O:26][C:27]1[CH:32]=[CH:31][C:30]([S:33](Cl)(=[O:35])=[O:34])=[CH:29][CH:28]=1>>[C:18]1([C:7]2[C:6]3[C:10](=[CH:11][CH:12]=[C:4]([NH:1][S:33]([C:30]4[CH:29]=[CH:28][C:27]([O:26][C:25]([F:24])([F:37])[F:38])=[CH:32][CH:31]=4)(=[O:35])=[O:34])[CH:5]=3)[NH:9][C:8]=2[C:13]([OH:15])=[O:14])[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: CCOC(=O)c1[nH]c2ccc([N+](=O)[O-])cc2c1-c1ccccc1
Reactant: O=S(=O)(Cl)c1ccc(OC(F)(F)F)cc1
Product: O=C(O)c1[nH]c2ccc(NS(=O)(=O)c3ccc(OC(F)(F)F)cc3)cc2c1-c1ccccc1

Procedure:
The title compound was prepared from ethyl 5-nitro-3-phenyl-1H-indole-2-carboxylate and 4-trifluoromethoxy-benzenesulfonyl chloride followed the procedures of Example 1 Step 2 & Step 3 as a dark brown solid: 1H NMR (DMSO-d6) δ 7.01 (d, J=1.8 Hz, 1H), 7.06 (dd, J=8.7, 1.9 Hz, 1H, 7.28-7.42 (m, 6H, 7.50 (d, J=6.9 Hz, 2H, 7.74 (d, J=8.9 Hz, 2H, 9.94 (s, 1H, 11.84 (s, 1H, 12.89 (br s, 1H; MS (ESI) m/z 475 [M-H]−; HRMS calcd for C22H16F3N2O5S: 477.0730; found (ESI+): 477.0719; Anal. calcd for C22H15F3N2O5S.0.15H2O: C, 55.15; H, 3.22; N, 5.85. Found: C, 54.95; H, 3.23; N, 5.93.
Reaction SMILES: C1C(=O)N([Br:8])C(=O)C1.[CH:9]([Si:12]([C:19]#[CH:20])([CH:16]([CH3:18])[CH3:17])[CH:13]([CH3:15])[CH3:14])([CH3:11])[CH3:10].CCCCC.O>CC(C)=O.[N+]([O-])([O-])=O.[Ag+]>[Br:8][C:20]#[C:19][Si:12]([CH:13]([CH3:14])[CH3:15])([CH:9]([CH3:11])[CH3:10])[CH:16]([CH3:18])[CH3:17]
Reactant: O=C1CCC(=O)N1Br
Reactant: C#C[Si](C(C)C)(C(C)C)C(C)C
Agent: [Ag+]
Agent: O=[N+]([O-])[O-]
Solvent: O
Solvent: CCCCC
Solvent: CC(C)=O
Product: CC(C)[Si](C#CBr)(C(C)C)C(C)C
Temperature: 25 °C
Reaction time: 2 h

Procedure:
NBS (2.14 g, 12 mmol) and AgNO3 (170 mg, 1 mmol) were added to a solution of triisopropylsilylacetylene (2.24 ml, 10 mmol) in acetone (15 ml). The solution was stirred for 2 hours at RT. Pentane (20 ml) and H2O (20 ml) were added and the solution was stirred for 30 minutes. The organic phase was extracted with pentane (3×20 ml) and dried over Na2SO4. The solvent was removed under reduced pressure at RT and the residue was used in the next reaction without any purification.
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[C:24]1[CH:29]=[CH:28][C:27]([CH3:30])=[C:26]([CH2:31][C:32]2[S:33][C:34](Cl)=[CH:35][CH:36]=2)[CH:25]=1)(=[O:3])[CH3:2].C([Sn](CCCC)(CCCC)[C:43]1[CH:44]=[N:45][CH:46]=[N:47][CH:48]=1)CCC.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.F[B-](F)(F)F.[H+].[F-].[Cs+]>O1CCOCC1.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[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[C:24]1[CH:29]=[CH:28][C:27]([CH3:30])=[C:26]([CH2:31][C:32]2[S:33][C:34]([C:43]3[CH:44]=[N:45][CH:46]=[N:47][CH:48]=3)=[CH:35][CH:36]=2)[CH:25]=1)(=[O:3])[CH3:2]
Reactant: CCCC[Sn](CCCC)(CCCC)c1cncnc1
Reactant: CC(=O)OC[C@H]1O[C@@H](c2ccc(C)c(Cc3ccc(Cl)s3)c2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Agent: [Pd]
Agent: CC(C)(C)P(C(C)(C)C)C(C)(C)C
Agent: F[B-](F)(F)F
Solvent: C1COCCO1
Product: CC(=O)OC[C@H]1O[C@@H](c2ccc(C)c(Cc3ccc(-c4cncnc4)s3)c2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Temperature: 100 °C
Yield: 41.1 %

Procedure:
A mixed solution of 1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-3-(5-chloro-2-thienylmethyl)-4-methylbenzene 57 (600 mg) obtained in Example 120-(1), tri-n-butyl(5-pyrimidinyl)tin (600 mg), tri-tert-butylphosphine•tetrafluoroboric acid adduct (116 mg), cesium fluoride (414 mg), and tris(dibenzylideneacetone) dipalladium (0) (91 mg) in 1,4-dioxane (18 ml) was heated under reflux at 100° C. for 3 hours under argon atmosphere. Insoluble materials were filtered off, and the filtrate was diluted with ethyl acetate and washed with brine. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=75:25-40:60) to give 1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-4-methyl-3-(5-(5-pyrimidinyl)-2-thienylmethyl)benzene (266 mg) as colorless crystals. APCI-Mass m/Z 597 (M+H). (2) The above 1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-4-methyl-3-(5-(5-pyrimidinyl)-2-thienylmethyl)benzene was used and treated in a manner similar to Example 106-(3) to give the target compound as colorless powder. APCI-Mass m/Z 429 (M+H).
Reaction SMILES: [CH3:1][C:2]1([CH3:9])[CH2:7][CH2:6][CH2:5][CH:4]([SH:8])[CH2:3]1.C(=O)([O-])[O-].[K+].[K+].[C:16]([C:18]1[CH:25]=[CH:24][C:21]([CH2:22]Br)=[CH:20][CH:19]=1)#[N:17]>C(#N)C.O>[CH3:1][C:2]1([CH3:9])[CH2:7][CH2:6][CH2:5][CH:4]([S:8][CH2:22][C:21]2[CH:24]=[CH:25][C:18]([C:16]#[N:17])=[CH:19][CH:20]=2)[CH2:3]1
Reactant: CC1(C)CCCC(S)C1
Reactant: N#Cc1ccc(CBr)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: O
Product: CC1(C)CCCC(SCc2ccc(C#N)cc2)C1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 37.1 %

Procedure:
To a solution of 3,3-dimethylcyclohexanethiol (0.6 g, 4.16 mmol) in acetonitrile (50 mL) add potassium carbonate (1.72 g, 12.48 mmol) and stir at room temperature for 10 min. Add 4-cyanobenzyl bromide (816 mg, 4.16 mmol) and stir the suspension for 18 h. Dilute with water (50 mL) and extract with EtOAc (50 mL). Dry the organic phase over MgSO4, filter and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (10:1) to obtain the desired intermediate as a clear oil (0.4 g, 37%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([Si:8]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)([CH3:15])[CH2:9][N:10]2[CH:14]=[N:13][CH:12]=[N:11]2)=[CH:4][CH:3]=1.C([Li])CCC.CN([CH:31]=[O:32])C>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([Si:8]([C:16]2[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=2)([CH3:15])[CH2:9][N:10]2[C:14]([CH:31]=[O:32])=[N:13][CH:12]=[N:11]2)=[CH:6][CH:7]=1
Reactant: CN(C)C=O
Reactant: C[Si](Cn1cncn1)(c1ccc(F)cc1)c1ccc(F)cc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: C[Si](Cn1ncnc1C=O)(c1ccc(F)cc1)c1ccc(F)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 80.1 %

Procedure:
Bis(4-fluorophenyl)methyl(1H-1,2,4-triazol-1-ylmethyl)silane (1.3 g, 0.004 mol) was lithiated as described in Example 1 using 3.7 mL (0.0044 mol) of 1.2M n-butyllithium in 10 mL of THF. DMF (1.2 mL, 0.016 mol) was added and the solution was allowed to warm to 0° C. After 1 hour, the reaction mixture was diluted with 1:1 ether/hexanes, washed with 7% aqueous NaHCO3 and brine, dried over Na2SO4 and evaporated. Flash chromatography using 10% ether/methylene chloride gave 1.1 g of the title compound as a clear oil: nD 1.5612; ir (neat) 2840, 1705, 1587, 1499, 1228, 1160, 1106, 821 cm-1 ; nmr (CDCl3) δ, 0.7 (3H, s), 4.7 (2H, s), 7.0 (4H, t), 7.4 (4H, m), 7.9 (1H, s), 9.8 (1H, s).