Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][N:8]=2)[N:3]=1.[CH2:18]([Zn]CC)[CH3:19].C([O-])([O-])=O.[K+].[K+]>C1COCC1>[CH2:18]([C:2]1[C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][N:8]=2)[N:3]=1)[CH3:19]
Reactant: CC[Zn]CC
Reactant: Clc1nc2cccnc2cc1-c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CCc1nc2cccnc2cc1-c1ccccc1
Reaction time: 6 h

Procedure:
2-Chloro-3-phenyl-1,5-naphthyridine was made according to a known procedure (WO 2005/100356). A mixture of 2-chloro-3-phenyl-1,5-naphthyridine (200 mg, 0.85 mmol), diethylzinc (0.87 mL, 1 M in hexane, 1.02 eq), K2CO3 (354 mg, 3.0 eq) and PdCl2(dppf)2 DCM complex (62.5 mg, 0.1 eq) in THF (5 mL) was purged with N2 for 5 min before heating to reflux. After 6 h, the reaction was quenched with NH4Cl and extracted with EtOAc and the residue was purified by silica gel column chromatography using hexane/DCM (2/3) as eluent to give a yellow solid. LC-MS (ESI) m/z 235 [M+H]+.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:17])[CH2:4][C:5](=[O:16])[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([O:12][CH2:13][CH2:14][CH3:15])[CH:7]=1.[CH2:18]1[O:28][C:27]2[CH:26]=[CH:25][C:22]([CH:23]=O)=[CH:21][C:20]=2[O:19]1>C1C=CC=CC=1.C(O)(=O)C.N1CCCCC1>[CH2:18]1[O:28][C:27]2[CH:26]=[CH:25][C:22](/[CH:23]=[C:4](/[C:5](=[O:16])[C:6]3[CH:11]=[CH:10][CH:9]=[C:8]([O:12][CH2:13][CH2:14][CH3:15])[CH:7]=3)\[C:3]([O:2][CH3:1])=[O:17])=[CH:21][C:20]=2[O:19]1
Reactant: CCCOc1cccc(C(=O)CC(=O)OC)c1
Reactant: O=Cc1ccc2c(c1)OCO2
Solvent: C1CCNCC1
Solvent: CC(=O)O
Solvent: c1ccccc1
Product: CCCOc1cccc(C(=O)/C(=C/c2ccc3c(c2)OCO3)C(=O)OC)c1
Yield: 478.3 %

Procedure:
To a solution of methyl-3-(Prop-1-yloxy)benzoylacetate (10 g, 4.2 mmol) in benzene (50 mL) was added 3,4-methylenedioxybenzaldehyde (6.36 g, 4.2 mmol) followed by piperidine (0.42 mL, 0.42 mmol) and glacial acetic acid (8 drops approx.). The mixture was refluxed for 2 h. and the volatiles removed in vacuo to give methyl (Z)-3-(3,4-methylenedioxyphenyl)-2-[3-(prop-1-yloxy)-benzoyl]propenoate (7.4 g, 48%) as an off white solid after titration with methanol (m.p. 122°-123° C.). Anal. Calc. for C21H20O6 : C, 68.47; H, 5.47. Found: C, 68.81; H, 5.49.
Reaction SMILES: C([N:8](CC1C=CC=CC=1)[C:9]1[CH:14]=[CH:13][C:12]([N:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]2)=[CH:11][C:10]=1[O:28][C:29]([F:32])([F:31])[F:30])C1C=CC=CC=1>CO.[Pd]>[NH2:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[CH2:16][CH2:17][N:18]([C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])[CH2:19][CH2:20]2)=[CH:11][C:10]=1[O:28][C:29]([F:31])([F:32])[F:30]
Reactant: CC(C)(C)OC(=O)N1CCN(c2ccc(N(Cc3ccccc3)Cc3ccccc3)c(OC(F)(F)F)c2)CC1
Agent: [Pd]
Solvent: CO
Product: CC(C)(C)OC(=O)N1CCN(c2ccc(N)c(OC(F)(F)F)c2)CC1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
To a solution of the product of EXAMPLE 45B (8.98 g, 16.63 mmol) in methanol (100 mL) was added 10% palladium on carbon (900 mg) and the mixture was stirred at ambient temperature under hydrogen for 5 hours. The catalyst was filtered off and the filtrate was concentrated to give the title compound. MS: 362 (M+H+).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([NH:11][CH2:12][C:13]1[CH2:18][CH2:17][C:16](=[O:19])[NH:15][N:14]=1)=[O:10].BrBr>C(O)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([NH:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16](=[O:19])[NH:15][N:14]=1)=[O:10]
Reactant: O=C(Cc1ccccc1F)NCC1=NNC(=O)CC1
Agent: BrBr
Solvent: CC(=O)O
Product: O=C(Cc1ccccc1F)NCc1ccc(=O)[nH]n1
Temperature: 50 °C
Reaction time: 3 h

Procedure:
458 g (1.740 mol) of the compound obtained in Example 1A were initially charged in acetic acid (2250 ml), and the mixture was warmed to 50° C. At this temperature, 98.16 ml (1.914 mol) of bromine were added dropwise with vigorous stirring, and stirring was then continued at 50° C. for 3 h. After cooling, the mixture was concentrated to dryness. The residue was stirred with saturated aqueous sodium bicarbonate solution (4800 ml). The mixture was then filtered and the precipitate was washed with a little water. The filtrate was extracted twice with ethyl acetate. The organic phases were combined, dried and concentrated. This gave 117 g of the target compound (25% of theory).
Reaction SMILES: [CH2:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:10]([CH3:13])([CH3:12])[CH3:11])[C:5]=1[OH:14])[CH:2]=[CH2:3].[C:15](Cl)(=[O:21])[CH2:16][CH2:17][CH2:18][C:19]#[CH:20].Cl[Sn](Cl)(Cl)Cl>C(Cl)Cl>[CH2:1]([C:4]1[CH:9]=[C:8]([C:15](=[O:21])[CH2:16][CH2:17][CH2:18][C:19]#[CH:20])[CH:7]=[C:6]([C:10]([CH3:13])([CH3:12])[CH3:11])[C:5]=1[OH:14])[CH:2]=[CH2:3]
Reactant: C#CCCCC(=O)Cl
Reactant: C=CCc1cccc(C(C)(C)C)c1O
Agent: Cl[Sn](Cl)(Cl)Cl
Solvent: ClCCl
Product: C#CCCCC(=O)c1cc(CC=C)c(O)c(C(C)(C)C)c1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 75 %

Procedure:
A solution of 2-allyl-6-t-butylphenol (0.57 g; 3 mmol) in dry CH2Cl2 (12 ml) is cooled to -78° C., and 5-hexynoyl chloride (0.43 g; 3.3 mmol) is added via syringe, followed by SnCl4 (0.375 ml) added dropwise via syringe, with stirring under Argon. After 30 min the reaction is allowed to warm to 0° C. and is stirred at that temperature for 5 min; it is then quenched with ca 1 ml of 3N HCl. The reaction is poured into 100 ml water and extracted with 3×50 ml portions of ether. The combined ether layers are washed with 150 ml portions of water until the aqueous layer is neutral (pH test). The ether layer is dried (MgSO4), filtered, and concentrated in vacuo to give crude product, which is chromatographed with 20:1 hexane/EtOAc, giving 0.64 g 2-allyl-4-(5-hexynoyl)-6-t-butylphenol (77% yield). The product is recrystallized from hexane at 0° C. to give crystals melting at 62°-63° C.
Reaction SMILES: [S:1]1[CH2:4][S:3][C:2]1=[C:5]([C:12](C(OOCC)=O)=[O:13])[C:6]([O:8][CH:9]([CH3:11])[CH3:10])=[O:7].[CH2:20]([NH2:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>C(Cl)Cl>[S:3]1[CH2:4][S:1][C:2]1=[C:5]([C:12](=[O:13])[NH:27][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:6]([O:8][CH:9]([CH3:10])[CH3:11])=[O:7]
Reactant: NCc1ccccc1
Reactant: CCOOC(=O)C(=O)C(C(=O)OC(C)C)=C1SCS1
Solvent: ClCCl
Product: CC(C)OC(=O)C(C(=O)NCc1ccccc1)=C1SCS1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
The mixture of isopropyl 2-(1,3-dithietan-2-ylidene)-2-(ethoxycarboxycarbonyl)acetate (15 g) and benzylamine (6.4 ml) in methylene chloride (150 ml) was stirred at room temperature for 4 hrs. The reaction mixture was then washed with dil-HCl and water to remove benzylamine. The solvent was evaporated and the residue was purified with ethyl acetate to give the titled compound as a white solid. (12.2 g, 77%).
Reaction SMILES: [CH3:1][CH:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([N+:11]([O-])=O)[CH:9]=2)[N:4]([CH:14]2[CH2:19][CH2:18][N:17]([CH3:20])[CH2:16][CH2:15]2)[C:3]1=[O:21].O.NN>CO.[Ni]>[NH2:11][C:8]1[CH:9]=[C:10]2[C:5](=[CH:6][CH:7]=1)[N:4]([CH:14]1[CH2:15][CH2:16][N:17]([CH3:20])[CH2:18][CH2:19]1)[C:3](=[O:21])[CH:2]2[CH3:1]
Reactant: CC1C(=O)N(C2CCN(C)CC2)c2ccc([N+](=O)[O-])cc21
Agent: [Ni]
Agent: NN
Solvent: O
Solvent: CO
Product: CC1C(=O)N(C2CCN(C)CC2)c2ccc(N)cc21
Yield: 95 %

Procedure:
A solution of compound 3-methyl-1-(1-methylpiperidin-4-yl)-5-nitroindolin-2-one (0.1 g, 0.345 mmol) in dry methanol (3 mL) was treated with Ra—Ni (0.05 g of wet slurry) followed by hydrazine hydrate (0.1 mL, 3.456 mmol) at room temperature. The resulting mixture was refluxed for 2 min. in a pre-heated oil bath and brought to room temperature. The reaction was filtered through celite bed and washed with methanol (3×10 mL). The combined methanol layer was evaporated and crude was purified by column chromatography (2 M NH3 in MeOH:CH2Cl2, 5:95) to obtain compound 5-amino-3-methyl-1-(1-methylpiperidin-4-yl)indolin-2-one (0.085 g, 96%) as a syrup. 1H NMR (DMSO-d6) δ: 1.24 (d, 3H, J=7.8 Hz), 1.42-1.54 (m, 2H), 1.96 (t, 2H, J=10.2 Hz), 2.18 (s, 3H), 2.26-2.34 (m, 2H), 2.85 (d, 2H, J=11.1 Hz), 3.25-3.30 (m, 1H), 3.91-4.02 (m, 1H), 4.75 (s, 2H), 6.43 (dd, 1H, J=2.1, 8.4 Hz), 6.56 (d, 1H, J=1.5 Hz), 6.79 (d, 1H, J=8.4 Hz); ESI-MS (m/z, %) 260 (MH+, 100).
Reaction SMILES: C(OC(N1CC2C([CH2:11][N:12]([CH2:16][C:17]3[S:18][C:19]4[C:24]([N:25]5[CH2:30][CH2:29][O:28][CH2:27][CH2:26]5)=[N:23][C:22]([Cl:31])=[N:21][C:20]=4[N:32]=3)[CH2:13]2)C1)=O)(C)(C)C.[CH:33]1([CH2:36][N:37]2[CH2:42]CNC[CH2:38]2)[CH2:35][CH2:34]1>>[Cl:31][C:22]1[N:23]=[C:24]([N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)[C:19]2[S:18][C:17]([CH2:16][N:12]3[CH2:11][CH2:42][N:37]([CH2:36][CH:33]4[CH2:35][CH2:34]4)[CH2:38][CH2:13]3)=[N:32][C:20]=2[N:21]=1
Reactant: CC(C)(C)OC(=O)N1CC2CN(Cc3nc4nc(Cl)nc(N5CCOCC5)c4s3)CC2C1
Reactant: C1CN(CC2CC2)CCN1
Product: Clc1nc(N2CCOCC2)c2sc(CN3CCN(CC4CC4)CC3)nc2n1

Procedure:
Prepared according to the method used in the preparation of 5-(5-chloro-7-morpholin-4-ylthiazolo[4,5-d]pyrimidin-2-ylmethyl)-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid tert-butyl ester using 1-cyclopropylmethylpiperazine in place of hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid tert-butyl ester. The title compound was obtained as a yellow solid (170 mg, 58%).
Reaction SMILES: C[O:2][C:3](=[O:28])/[C:4](/[C:12]1[CH:17]=[CH:16][C:15]([N:18]2[C:22]([CH3:23])=[N:21][N:20]=[N:19]2)=[C:14]([C:24]([F:27])([F:26])[F:25])[CH:13]=1)=[CH:5]/[CH2:6][CH:7]1[CH2:11][CH2:10][CH2:9][CH2:8]1.[OH-].[Na+]>C(O)C>[CH:7]1([CH2:6]/[CH:5]=[C:4](\[C:12]2[CH:17]=[CH:16][C:15]([N:18]3[C:22]([CH3:23])=[N:21][N:20]=[N:19]3)=[C:14]([C:24]([F:25])([F:27])[F:26])[CH:13]=2)/[C:3]([OH:28])=[O:2])[CH2:11][CH2:10][CH2:9][CH2:8]1
Reactant: COC(=O)/C(=C/CC1CCCC1)c1ccc(-n2nnnc2C)c(C(F)(F)F)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: Cc1nnnn1-c1ccc(/C(=C\CC2CCCC2)C(=O)O)cc1C(F)(F)F
Temperature: 47.5 °C
Yield: 99.3 %

Procedure:
A solution of (E)-4-cyclopentyl-2-[4-(5-methyl-tetrazol-1-yl)-3-trifluoromethyl-phenyl]-but-2-enoic acid methyl ester (359 mg, 0.9 mmol) in ethanol (5 mL) was treated with a lN aqueous sodium hydroxide solution (3 mL). The solution was heated at 45-50° C. for 15 h, at which time, thin layer chromatography analysis of the reaction mixture indicated the absence of starting material. The reaction mixture was concentrated in vacuo to remove ethanol. The residue was diluted with water (20 mL) and extracted with diethyl ether (1×30 mL) to remove any neutral impurities. The aqueous layer was then acidified with a 1N aqueous hydrochloric acid solution, and the resulting acid was extracted into ethyl acetate (2×30 mL). The combined organic layers were washed with a saturated aqueous sodium chloride solution (1×50 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo to afford (E)-4-cyclopentyl-2-[4-(5-methyl-tetrazol-1-yl)-3-trifluoromethyl-phenyl]-but-2-enoic acid (340 mg, 98%) as a yellow solid: EI-HRMS m/e calcd for C18H19F3N4O2 (M+) 380.1460, found 380.1460.
Reaction SMILES: Br[C:2]1[C:3]([F:19])=[CH:4][C:5]2[O:11][CH2:10][CH2:9][N:8]3[CH:12]=[C:13]([C:15]([NH2:17])=[O:16])[N:14]=[C:7]3[C:6]=2[CH:18]=1.[N:20]1([C:24](=[O:30])[C:25]([OH:29])([CH3:28])[C:26]#[CH:27])[CH2:23][CH2:22][CH2:21]1>>[N:20]1([C:24](=[O:30])[C:25]([OH:29])([CH3:28])[C:26]#[C:27][C:2]2[C:3]([F:19])=[CH:4][C:5]3[O:11][CH2:10][CH2:9][N:8]4[CH:12]=[C:13]([C:15]([NH2:17])=[O:16])[N:14]=[C:7]4[C:6]=3[CH:18]=2)[CH2:21][CH2:22][CH2:23]1
Reactant: C#CC(C)(O)C(=O)N1CCC1
Reactant: NC(=O)c1cn2c(n1)-c1cc(Br)c(F)cc1OCC2
Product: CC(O)(C#Cc1cc2c(cc1F)OCCn1cc(C(N)=O)nc1-2)C(=O)N1CCC1
Yield: 22 %

Procedure:
Similar to as described in General Procedure G, 10-bromo-9-fluoro-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide was reacted with 1-(azetidin-1-yl)-2-hydroxy-2-methylbut-3-yn-1-one to give the titled compound as a yellow solid (40 mg, 22%).
Reaction SMILES: CC1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/CO.[BrH:22].[C:23]1([PH+:29]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>C1(C)C=CC=CC=1>[Br-:22].[C:36]1([PH+:29]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1
Reactant: Br
Agent: CC1=C(/C=C/C(C)=C/C=C/C(C)=C/CO)C(C)(C)CCC1
Agent: c1ccc([PH+](c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: [Br-]
Temperature: 60 °C
Reaction time: 2 h

Procedure:
Retinol (2 g, 7 mmol) is dissolved in 50 ml of toluene and 2.4 g (7 mmol) of triphenylphosphonium hydrobromide is added. The mixture is stirred for 18 hours at room temperature and 2 hours at 60° C., then cooled and the toluene separated. The viscous sediment is digested four times with 25 ml of dry toluene. The final sediment is dissolved in 100 ml of methylene chloride. The solution is evaporated under reduced pressure and dried in vacuo to give retinyl triphenyl phosphonium bromide. This substance is dissolved in 40 ml of DMF and the resulting solution is cooled to -10° C. and 0.3 g of NaH, (50% dispersion in oil) is added carefully. The mixture is stirred for 2 hours and 4 g (0.07 mol) of acetone is added dropwise. After two hours at -10° C., the reaction mixture is stirred at room temperature for 18 hours and poured into 600 ml of ice-H2O mixture. The mixture is extracted several times with hexane. The combined organic layers are washed with a mixture of methanol-H2O (3:2, v/v) and brine, dried (Na2SO4), and evaporation of solvent under reduced pressure affords the crude product. Purification of the crude product with a dry column (hexane:petroleum ether, 1:1) gives 2,5,9-trimethyl-11-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8,10-undecapentaene.
Reaction SMILES: [K].[C:2]([O:5][C:6]1[CH:15]=[CH:14][C:13]([CH:16]=[CH:17][C:18]2[CH:23]=[CH:22][C:21]([S:24]([OH:27])(=O)=[O:25])=[CH:20][CH:19]=2)=[CH:12][C:7]=1[C:8]([O:10][CH3:11])=[O:9])(=[O:4])[CH3:3].CN(C)C=O.S(Cl)([Cl:35])=O.[OH-].[Na+]>ClCCl.O>[C:2]([O:5][C:6]1[CH:15]=[CH:14][C:13]([CH:16]=[CH:17][C:18]2[CH:23]=[CH:22][C:21]([S:24]([Cl:35])(=[O:27])=[O:25])=[CH:20][CH:19]=2)=[CH:12][C:7]=1[C:8]([O:10][CH3:11])=[O:9])(=[O:4])[CH3:3]
Reactant: COC(=O)c1cc(C=Cc2ccc(S(=O)(=O)O)cc2)ccc1OC(C)=O
Reactant: O=S(Cl)Cl
Agent: [K]
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)c1cc(C=Cc2ccc(S(=O)(=O)Cl)cc2)ccc1OC(C)=O
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Methyl 2-acetyloxy-5-[2-(4-sulfophenyl)ethenyl]benzoate potassium salt (42.4 g, 0.104 mol) was suspended in dichloromethane. Dimethylformamide (5 ml) and thionyl chloride were added, and the mixture refluxed with stirring for 3 h. After cooling to room temperature, water (15 ml) was added. By careful addition of 5M sodium hydroxide, the pH of the aqueous phase was adjusted to about 7. The phases were separated and the organic phase washed with water. The solution was dried (MgSO4), treated with activated carbon and filtered. After evaporation of the solvent, the solid residue was recrystallized from a toluene and petroleum ethermixture. Yield 29.3 g (71%).
Reaction SMILES: C(O[C@@H:6]1[O:20][C@H:19]([C@@H:21]([CH2:27][O:28][C:29](=[O:32])[CH2:30][CH3:31])[O:22][C:23](=[O:26])[CH2:24][CH3:25])[C@H:13]([O:14][C:15](=[O:18])[CH2:16][CH3:17])[C@H:7]1[O:8][C:9](=[O:12])[CH2:10][CH3:11])(=O)CC.[CH3:33][S:34][Si](C)(C)C.FC(F)(F)S(O[Si](C)(C)C)(=O)=O>ClCCCl.C(Cl)(Cl)Cl>[C:9]([O:8][C@@H:7]1[C@@H:13]([O:14][C:15](=[O:18])[CH2:16][CH3:17])[C@@H:19]([C@@H:21]([CH2:27][O:28][C:29](=[O:32])[CH2:30][CH3:31])[O:22][C:23](=[O:26])[CH2:24][CH3:25])[O:20][C@H:6]1[S:34][CH3:33])(=[O:12])[CH2:10][CH3:11]
Reactant: CS[Si](C)(C)C
Reactant: CCC(=O)OC[C@@H](OC(=O)CC)[C@H]1O[C@@H](OC(=O)CC)[C@H](OC(=O)CC)[C@H]1OC(=O)CC
Agent: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Solvent: ClCCCl
Solvent: ClC(Cl)Cl
Product: CCC(=O)OC[C@@H](OC(=O)CC)[C@H]1O[C@@H](SC)[C@H](OC(=O)CC)[C@H]1OC(=O)CC
Temperature: 50 °C
Reaction time: 0.33 h
Yield: 83.2 %

Procedure:
1,2,3,5,6-Penta-O-propanoyl-β-D-glucofuranose (614 mg, 1.3 mmol) was dissolved in 1,2-dichloroethane (5 mL) and cooled to 0° C. (Methylthio)trimethylsilane (567 μL, 4.0 mmol) was added dropwise followed by trimethylsilyl trifluoromethanesulfonate (72 μL, 0.4 mmol). After 20 min at room temperature, the mixture was heated at 50° C. for 3 h, cooled, diluted with CHCl3, washed with 50% aqueous NaHCO3 (30 mL), brine, dried (MgSO4) and concentrated in vacuo. Flash silica chromatography of the residue, eluting with 10% ethyl acetate in petroleum ether, gave methyl 2,3,5,6-tetra-O-propanoyl-1-thio-β-D-glucofuranoside as a colourless solid (470 mg, 81%). A sample was recrystallised from ethanol to give colourless needles, mp 62-63° C. (from EtOH), [α]D22=−50.5 (c 1.0 in CHCl3), (Found: C, 52.7; H, 7.2; S, 7.4. C19H30O9S requires C, 52.5; H, 7.0; S 7.4%); δH (CDCl3) 5.37 (1H, d, J 4.2, 3-H), 5.33 (1H, ddd, J 9.3, 5.1 and 2.5, 5-H), 5.07 (1H, d, J 2.2, 2-H), 5.00 (1H, d, J 2.2, 1-H), 4.62 (1H, dd, J 12.3 and 5.1, 2.5, 6a-H), 4.36 (1H, dd, J 9.3 and 4.2, 4-H), 4.17 (1H, dd, J 12.3 and 5.1, 6b-H), 2.39 (2H, q, J 7.6, CH2), 2.37 (2H, q, J 7.6, CH2), 2.35 (2H, q, J 7.6, CH2), 2.26 (2H, q, J 7.6, CH2), 2.23 (3H, s, SCH3) 1.16 (3H, t, J 7.6, CH3), 1.14 (3H, t, J 7.6, CH3), 1.13 (3H, t, J 7.6, CH3), 1.09 (3H, t, J 7.6, CH3); δC (CDCl3) 174.4, 173.3, 173.1, 173.1 (4×C═O), 89.6 (1-C), 81.6 (2-C), 79.1 (4-C), 74.7 (3-C), 68.4 (5-C), 63.4 (6-C), 27.7 (4×CH2), 9.4, 9.2, 9.2, 9.1 (4×CH3); m/z (FAB) 435.169691 (MH+, C19H31O9S requires 435.168880).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[N:3]=1.C([Li])CCC.CN(C)[CH:16]=[O:17].Cl>CCOCC.CCCCCC>[Br:8][C:4]1[N:3]=[C:2]([CH:16]=[O:17])[CH:7]=[CH:6][CH:5]=1
Reactant: Brc1cccc(Br)n1
Reactant: CN(C)C=O
Agent: Cl
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: CCCCCC
Product: O=Cc1cccc(Br)n1
Temperature: -78 °C
Reaction time: 0.08 h
Yield: 76.8 %

Procedure:
2,6-Dibromopyridine (25 g, 0.105 mol) is suspended in 200 ml of ether. The solution is cooled to -78° C. and n-butyllithium (65.6 ml, 1.6M, 0.105 mol) in hexane is added slowly dropwise over a 1.5 hour period. After 5 minutes, dimethylformamide (8.4 g, 0.115 mol) in 13 ml of ether is added slowly dropwise over one hour. The reaction is allowed to stir at -78° C. for 1.5 hours. The mixture is warmed to -25° C. and 40 ml of 6N hydrochloric acid is added. The mixture is allowed to warm to room temperature. The aqueous phase is extracted three times with ether and the combined organics are washed once with water, dried over sodium sulfate and evaporated. Trituration with pentane afforded 15.0 g of the title compound as a tannish-white solid.
Reaction SMILES: [CH3:1][C:2]1[S:6][C:5]([NH2:7])=[N:4][CH:3]=1.Br[C:9]1[C:10](=[O:17])[N:11]([CH3:16])[CH:12]=[C:13]([Br:15])[CH:14]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Br:15][C:13]1[CH:14]=[C:9]([NH:7][C:5]2[S:6][C:2]([CH3:1])=[CH:3][N:4]=2)[C:10](=[O:17])[N:11]([CH3:16])[CH:12]=1
Reactant: Cn1cc(Br)cc(Br)c1=O
Reactant: Cc1cnc(N)s1
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Product: Cc1cnc(Nc2cc(Br)cn(C)c2=O)s1
Temperature: 25 °C
Yield: 83.3 %

Procedure:
A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 1,4-dioxane (50 mL), 5-methylthiazol-2-amine (2.28 g, 20.0 mmol), 3,5-dibromo-1-methylpyridin-2(1H)-one (5.34 g, 20.0 mmol) cesium carbonate (13.0 g, 40.0 mmol), xantphos (1.16 g, 2.0 mmol), and tris(dibenzylideneacetone)dipalladium(0) (916 mg, 1.0 mmol). The system was subjected to three cycles of vacuum/argon flush and heated at reflux for 5 h. It was then cooled to room temperature and filtered. The solid was washed with dichloromethane (3×50 mL). The combined filtrate was concentrated under reduced pressure and the residue was washed with acetonitrile (30 mL) to afford 120a (5 g, crude, 83%) as a yellow solid. MS-ESI: [M+H]+ 300.1.
Reaction SMILES: [Br:1][C:2]1[N:7]=[C:6]([CH2:8][OH:9])[CH:5]=[CH:4][C:3]=1[O:10][C:11]([CH3:15])([C:13]#[CH:14])[CH3:12]>C1(C)C=CC=CC=1>[Br:1][C:2]1[N:7]=[C:6]([CH2:8][OH:9])[CH:5]=[C:4]2[CH:14]=[CH:13][C:11]([CH3:15])([CH3:12])[O:10][C:3]=12
Reactant: C#CC(C)(C)Oc1ccc(CO)nc1Br
Solvent: Cc1ccccc1
Product: CC1(C)C=Cc2cc(CO)nc(Br)c2O1
Temperature: 25 °C

Procedure:
A solution of 31 (700 mg, 2.5 mmol) in toluene (10 mL) was subjected to microwave irradiation (200 W, 120° C.) for 1 h. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated under vacuum and the residue purified by column chromatography (silica gel, EA:Hex 1:3-1:2). Yield: 500 mg, 70%. 1H NMR (CDCl3): δ 6.88 (s, 1H), 6.28 (d, J=10 Hz, 1H), 5.90 (d, J=9.6 Hz, 1H), 4.63 (s, 2H), 1.51 ppm (s, 6H).
Reaction SMILES: CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C1=CC=CC=2)=O.[C:23]([C:27]1[O:28][C:29]([CH2:36][OH:37])=[CH:30][C:31]=1[S:32]([NH2:35])(=[O:34])=[O:33])([CH3:26])([CH3:25])[CH3:24].S([O-])([O-])(=O)=S.[Na+].[Na+]>C(Cl)Cl>[C:23]([C:27]1[O:28][C:29]([CH:36]=[O:37])=[CH:30][C:31]=1[S:32]([NH2:35])(=[O:34])=[O:33])([CH3:26])([CH3:24])[CH3:25]
Reactant: CC(C)(C)c1oc(CO)cc1S(N)(=O)=O
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: ClCCl
Product: CC(C)(C)c1oc(C=O)cc1S(N)(=O)=O
Reaction time: 0.42 h
Yield: 89.8 %

Procedure:
At room temperature, 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3 (1H)-one (0.60 g) was added to a solution of 2-tert-butyl-5-hydroxymethyl-furan-3-sulfonamide (0.30 g) in methylene chloride (10 ml), followed by stirring for 25 min. The reaction mixture was mixed with a 20% aqueous sodium thiosulfate solution, extracted with methylene chloride. The organic layer was washed with a saturated aqueous sodium bicarbonate solution, dried over magnesium sulfate and evaporated under reduced pressure to remove the solvent; the thus obtained residue was subjected to silica gel column chromatography (developing solvent: n-hexane:ethyl acetate=2:1) to give the titled compound (267 mg, 90%).
Reaction SMILES: C[O:2][C:3](=[O:22])[C:4]1[CH:9]=[C:8]([S:10][C:11]2[C:19]3[C:14](=[CH:15][C:16]([Cl:20])=[CH:17][CH:18]=3)[NH:13][C:12]=2[CH3:21])[CH:7]=[N:6][CH:5]=1.[CH2:23](Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[H-].[Na+].Cl>CN(C=O)C.C1COCC1>[CH2:23]([N:13]1[C:14]2[C:19](=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=2)[C:11]([S:10][C:8]2[CH:7]=[N:6][CH:5]=[C:4]([CH:9]=2)[C:3]([OH:2])=[O:22])=[C:12]1[CH3:21])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: BrCc1ccccc1
Reactant: COC(=O)c1cncc(Sc2c(C)[nH]c3cc(Cl)ccc23)c1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: Cc1c(Sc2cncc(C(=O)O)c2)c2ccc(Cl)cc2n1Cc1ccccc1
Temperature: 0 °C

Procedure:
5-(6-Chloro-2-methyl-1H-indol-3-ylsulfanyl)-nicotinic acid methyl ester and benzyl bromide (0.0267 mL, 0.225 mmol) were dissolved in DMF:THF (1:1, 4 mL). The mixture was cooled to 0° C., sodium hydride (60% in mineral oil, 0.015 g, 0.375 mmol) was added, and the ice bath was removed. After warming to room temperature, the reaction was heated to 50° C. for 1 hour. Analytical LCMS indicated complete conversion and, furthermore, complete hydrolysis of the methyl ester. The reaction was neutralized with HCl (aq.), diluted with EtOAc/hexanes and washed with H2O/brine. The organic portion was dried and concentrated and the residue was purified via preparatory HPLC (10-100% ACN in H2O, 20 minute run, r.t.=13.1 minutes) to give the title compound. Mass spectrometric data: [M+H]+=409.