Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:4][CH2:5][C:6]1[S:7][CH:8]=[C:9](Br)[N:10]=1)(=[O:3])[CH3:2].C[Sn](C)C.C[Sn](C)C.N1(C2SC=[C:29]([Sn:31](C)([CH3:33])[CH3:32])N=2)CCCCC1>C1(C)C=CC=CC=1.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>[C:1]([O:4][CH2:5][C:6]1[S:7][CH:8]=[C:9]([Sn:31]([CH3:33])([CH3:32])[CH3:29])[N:10]=1)(=[O:3])[CH3:2]
Reactant: C[Sn](C)(C)c1csc(N2CCCCC2)n1
Reactant: CC(=O)OCc1nc(Br)cs1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: C[Sn](C)C
Solvent: Cc1ccccc1
Product: CC(=O)OCc1nc([Sn](C)(C)C)cs1

Procedure:
2-Acetoxymethyl-4-bromothiazole (387) was taken up in degassed toluene (0.1 M), and was then treated hexamethylditin (10 equiv) and tetrakis(triphenylphosphine)palladium(0) (0.1 equiv) at 80° C. for 3 h according to the procedure described for the synthesis of 2-piperidinyl-4-(trimethylstannyl)thiazole (373), to yield, after flash column chromatography (silica gel, 5% NEt, in hexanes), 2-dacetoxymethyl-4-(trimethylstannyl)thiazole (388; 100%).
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]2[CH:8]=[N:9][N:10]([C:11]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:4]=2[CH:3]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.C[Si]([N-:59][Si](C)(C)C)(C)C.[Li+]>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].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.C1COCC1>[C:11]([N:10]1[C:4]2[CH:3]=[C:2]([NH2:59])[N:7]=[CH:6][C:5]=2[CH:8]=[N:9]1)([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1
Reactant: Clc1cc2c(cn1)cnn2C(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: [Li+]
Solvent: C1CCOC1
Product: Nc1cc2c(cn1)cnn2C(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 70 °C
Reaction time: 16 h
Yield: 83.7 %

Procedure:
A microwave vial was charged with 6-chloro-1-trityl-1H-pyrazolo[4,3-c]pyridine (1.02 g, 2.58 mmol), Pd2(dba)3 (0.24 g, 0.262 mmol), 2-(dicyclohexylphosphino) biphenyl (0.1 g, 0.285 mmol) and THF (11 mL). The mixture was evacuated and purged with nitrogen 5 times. Lithium bis(trimethylsilyl)amide (4.0 ml, 4.0 mmol, 1M in THF) was added dropwise and the mixture was heated at 70° C. for 2 h. Pd2(dba)3 (0.12 g, 0.131 mmol), 2-(dicyclohexylphosphino) biphenyl (0.05 g, 0.142 mmol) and LiHMDS (2.0 ml, 2.0 mmol, 1M in THF) were added again. After 16 h, the mixture was quenched with saturated NH4Cl and extracted with 2-methyltetrahydrofuran. The organic phase was washed with water, brine, dried (Na2SO4) and concentrated in vacuo to afford a residue, which was purified by chromatography on silica gel (MeOH in DCM, 0-8% 15 CV, 8-10% 10 CV) to afford 1-trityl-1H-pyrazolo[4,3-c]pyridin-6-amine (0.813 g, 2.16 mmol, 84%). MS ESI calc'd. for C25H21N4 [M+H]+ 377, found 377.
Reaction SMILES: [CH3:1][S:2]([CH2:5][CH:6]([OH:9])[CH2:7][OH:8])(=[O:4])=[O:3].N1C=CC=CC=1.C1(C)C=CC=CC=1.Cl[C:24](Cl)([O:26]C(=O)OC(Cl)(Cl)Cl)Cl>C(Cl)Cl.O>[CH3:1][S:2]([CH2:5][CH:6]1[CH2:7][O:8][C:24](=[O:26])[O:9]1)(=[O:4])=[O:3]
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: CS(=O)(=O)CC(O)CO
Solvent: Cc1ccccc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: CS(=O)(=O)CC1COC(=O)O1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 19.5 %

Procedure:
5.70 g (37.0 mmol) of 3-(methylsulfonyl)propane-1,2-diol and 17.56 g (220.0 mol) of pyridine were dissolved in 100 mL of methylene chloride, and 20 mL of a toluene solution of 10.97 g (37.0 mmol) of triphosgene was dropwise added to the solution at an inner temperature of from 5° C. to 15° C., taking 30 minutes, and stirred at room temperature for 1 hour. 20 mL of water was added thereto for liquid-liquid separation, and the organic layer was dried with magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from dimethyl carbonate/acetonitrile to give 1.30 g of the intended 4-(methylsulfonylmethyl)-1,3-dioxolan-2-one (yield 20%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:8]=[C:9]=[O:10])[CH:5]=[CH:6][CH:7]=1.Cl.[NH2:12][CH2:13][C:14]1[CH:22]=[CH:21][CH:20]=[C:19]2[C:15]=1[CH2:16][N:17]([CH:24]1[CH2:29][CH2:28][C:27](=[O:30])[NH:26][C:25]1=[O:31])[C:18]2=[O:23].C(N(CC)CC)C>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]([NH:12][CH2:13][C:14]2[CH:22]=[CH:21][CH:20]=[C:19]3[C:15]=2[CH2:16][N:17]([CH:24]2[CH2:29][CH2:28][C:27](=[O:30])[NH:26][C:25]2=[O:31])[C:18]3=[O:23])=[O:10])[CH:5]=[CH:6][CH:7]=1
Reactant: NCc1cccc2c1CN(C1CCC(=O)NC1=O)C2=O
Reactant: O=C=Nc1cccc(Cl)c1
Agent: Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=C1CCC(N2Cc3c(CNC(=O)Nc4cccc(Cl)c4)cccc3C2=O)C(=O)N1
Temperature: 5 °C
Reaction time: 0.17 h
Yield: 89.2 %

Procedure:
3-Chlorophenyl isocyanate (0.4 g, 2.7 mmol) was added to a stirred suspension of 3-(4-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hydrochloride (0.7 g, 2.1 mmol) and triethylamine (0.3 g, 2.9 mmol) in THF (30 mL) at 5-10° C. After stirring at 5° C. for 10 minutes, the mixture was stirred at room temperature overnight. The reaction was quenched with methanol (1 mL) and then concentrated. The residue was stirred with 1N HCl (30 mL) for 1 hour and filtered. The solid was slurried with hot methanol (15 mL) to give 1-(3-chloro-phenyl)-3-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-urea (0.8 g, 91%): mp 250-252° C.; 1H NMR (DMSO-d6) δ 2.00-2.05 (m, 1H), 2.37-2.65 (m, 2H), 2.86-2.98 (m, 1H), 4.37 (d, J=5.3 Hz, 2H, CH2), 4.44 (d, J=17.2 Hz, 1H), 4.51 (d, J=17.3 Hz, 1H), 5.11-5.18 (dd, J=4.9 and 13.1 Hz, 1H, CH), 6.82 (t, J=5.4 Hz, 1H, NH), 6.92-6.95 (m, 1H, Ar), 7.18-7.27 (m, 2H, Ar), 7.48-7.65 (m, 4H, Ar), 8.84 (s, 1H, NH), 11.01 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.57, 31.18, 39.68, 46.20, 51.59, 116.15, 117.13, 120.78, 121.57, 128.30, 130.21, 130.35, 131.64, 133.06, 135.37, 139.90, 141.86, 154.99, 168.07, 171.00, 172.82; Anal. calcd. for C21H19N4O4Cl: C, 59.09; H, 4.49; N, 13.13; Cl, 8.31. Found: C, 59.06; H, 4.39; N, 13.24; Cl, 7.95.
Reaction SMILES: [CH3:1][C:2]([CH3:31])([CH3:30])[C@H:3]([NH:8][C:9]([N:11]1[C:19]2[CH2:18][CH2:17][N:16](C)[CH2:15][C:14]=2[C:13]([C:21]2[CH:26]=[C:25]([F:27])[C:24]([F:28])=[CH:23][C:22]=2F)=[N:12]1)=[O:10])[C:4]([NH:6][CH3:7])=[O:5].FC1C=C(C2C3CN(C(OC(C)(C)C)=O)CCC=3NN=2)C=CC=1F.C=O>>[F:27][C:25]1[CH:26]=[C:21]([C:13]2[C:14]3[CH2:15][NH:16][CH2:17][CH2:18][C:19]=3[N:11]([C:9]([NH:8][C@@H:3]([C:2]([CH3:31])([CH3:30])[CH3:1])[C:4]([NH:6][CH3:7])=[O:5])=[O:10])[N:12]=2)[CH:22]=[CH:23][C:24]=1[F:28]
Reactant: CNC(=O)[C@@H](NC(=O)n1nc(-c2cc(F)c(F)cc2F)c2c1CCN(C)C2)C(C)(C)C
Agent: C=O
Agent: CC(C)(C)OC(=O)N1CCc2[nH]nc(-c3ccc(F)c(F)c3)c2C1
Product: CNC(=O)[C@@H](NC(=O)n1nc(-c2ccc(F)c(F)c2)c2c1CCNC2)C(C)(C)C

Procedure:
Compound 52 was prepared according to the procedure described for the synthesis of compound 37 by replacing intermediate 19 with intermediate 15, without the reductive amination step with formaldehyde. 1H NMR (CDCl3) δ 7.92 (d, J=9.4 Hz, 1H), 7.50-7.55 (m, 1H), 7.37-7.40 (m, 1H), 7.19-7.26 (m, 1H), 6.10 (br, 1H), 4.15 (d, J=9.4 Hz, 1H), 4.04 (s, 1H), 3.09-3.15 (m, 4H), 2.85 (d, J=4.8 Hz, 3H), 1.06 (s, 9H). LCMS (+ESI) m/z=406.2 [M+H]+.
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]([SH:7])=[N:5][N:6]=1.[C:8](O)(=[O:10])[CH3:9]>>[C:8]([NH:1][C:2]1[S:3][C:4]([SH:7])=[N:5][N:6]=1)(=[O:10])[CH3:9]
Reactant: Nc1nnc(S)s1
Reactant: CC(=O)O
Product: CC(=O)Nc1nnc(S)s1
Temperature: 100 °C

Procedure:
Polyphosphoric acid (190 grams) and acetic acid (406 grams) were charged into a glass reaction vessel fitted with a mechanical stirrer and thermometer and heated, with stirring, to 100° C. To this heated, stirred mixture was then added 2-amino-5-mercapto-1,3,4-thiadiazole (250 grams). Stirring was continued for an additional hour at a temperature of 120° C. The reaction mixture was then cooled to 60° C. and poured over ice. A precipitate formed which was filtered and air dried to yield the desired product 2-acetamido-5-mercapto-1,3,4-thiadiazole having a melting point greater than 290° C.
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[C:12]([CH3:14])[C:7]2[O:8][CH2:9][CH2:10][O:11][C:6]=2[C:5]=1[CH3:15])([O-])=O.[H][H]>[Pd].C(O)C>[NH2:1][C:4]1[CH:13]=[C:12]([CH3:14])[C:7]2[O:8][CH2:9][CH2:10][O:11][C:6]=2[C:5]=1[CH3:15]
Reactant: Cc1cc([N+](=O)[O-])c(C)c2c1OCCO2
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: Cc1cc(N)c(C)c2c1OCCO2
Temperature: 25 °C
Reaction time: 3 h
Yield: 97.9 %

Procedure:
A mixture of 3.10 g of 6-nitro-5,8-dimethyl-1,4-benzodioxane and 0.30 g of 10% palladium on carbon in 75 mL of ethanol is placed under a 50 psi hydrogen atmosphere. The mixture is shaken for three hours at room temperature. The reaction mixture is filtered through Celite to yield a brownish solution. Concentration under reduced pressure affords 2.6 g of 6-amino-5,8-dimethyl-1,4-benzodioxane.
Reaction SMILES: C([O:3][C:4](=O)[CH2:5][CH2:6][CH2:7][N:8]1[CH2:13][CH2:12][CH:11]([C:14]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)[OH:15])[CH2:10][CH2:9]1)C.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[F:22][C:19]1[CH:18]=[CH:17][C:16]([C:14]([C:23]2[CH:24]=[CH:25][C:26]([F:29])=[CH:27][CH:28]=2)([OH:15])[CH:11]2[CH2:12][CH2:13][N:8]([CH2:7][CH2:6][CH2:5][CH2:4][OH:3])[CH2:9][CH2:10]2)=[CH:21][CH:20]=1
Reactant: CCOC(=O)CCCN1CCC(C(O)(c2ccc(F)cc2)c2ccc(F)cc2)CC1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: OCCCCN1CCC(C(O)(c2ccc(F)cc2)c2ccc(F)cc2)CC1
Reaction time: 0.5 h
Yield: 80.6 %

Procedure:
A solution of 15.4 g (0.037 mol) of 4-[bis(4-fluorophenyl)hydroxymethyl]-1-piperidinebutanoic acid ethyl ester in 100 mL of dry (freshly distilled from lithium aluminum hydride) tetrahydrofuran was added dropwise to a mixture of 3.5 g (0.092 mol) of lithium aluminum hydride in 100 mL of dry tetrahydrofuran. After the final addition, the mixture was stirred at ambient temperature for 3 h, whereupon the excess lithium aluminum hydride was quenched by successive dropwise additions of 4 mL of water, 4 mL of 15% sodium hydroxide solution and 12 mL of water. The mixture was stirred for 30 min, filtered, and the filtrate concentrated under reduced pressure to yield 11.2 g (100%) of an oil which crystallized upon standing. A portion of the solid was recrystallized from ethyl acetate/petroleum ether (30°-60° C.) to give the title compound as a light-tan solid, mp 130°-131° C.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][C:5]2[S:8][C:9]([C:11]([O:13]CC)=[O:12])=[CH:10][C:4]=2[CH2:3]1.FC(F)(F)C([O-])=O>>[CH3:1][N:2]1[CH2:7][CH2:6][C:5]2[S:8][C:9]([C:11]([OH:13])=[O:12])=[CH:10][C:4]=2[CH2:3]1
Reactant: CCOC(=O)c1cc2c(s1)CCN(C)C2
Agent: O=C([O-])C(F)(F)F
Product: CN1CCc2sc(C(=O)O)cc2C1

Procedure:
Prepared analogously to Example 45b from ethyl 5-methyl-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine-2-carboxylate (as the trifluoroacetate salt).
Reaction SMILES: Cl[C:2]1[CH:11]=[C:10]([C:12]([NH:14][CH2:15][CH2:16][N:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)=[O:13])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:22])[CH:8]=2)[N:3]=1.Cl.[O:24]1[CH2:29][CH2:28][N:27]([CH2:30][C:31]2[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=2)[CH2:26][CH2:25]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.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>[Cl:22][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([C:34]1[CH:33]=[CH:32][C:31]([CH2:30][N:27]3[CH2:28][CH2:29][O:24][CH2:25][CH2:26]3)=[CH:36][CH:35]=1)[CH:11]=[C:10]2[C:12]([NH:14][CH2:15][CH2:16][N:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1)=[O:13]
Reactant: OB(O)c1ccc(CN2CCOCC2)cc1
Reactant: O=C(NCCN1CCCC1)c1cc(Cl)nc2ccc(Cl)cc12
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: Cl
Agent: O=P([O-])([O-])[O-]
Solvent: CN(C)C=O
Solvent: O
Product: O=C(NCCN1CCCC1)c1cc(-c2ccc(CN3CCOCC3)cc2)nc2ccc(Cl)cc12
Temperature: 130 °C
Reaction time: 0.3 h
Yield: 29.8 %

Procedure:
In a sealed 5 ml microwave vial, a suspension of 2,6-dichloro-N-(2-pyrrolidin-1-ylethyl)quinoline-4-carboxamide (preparation 9) (158 mg, 0.47 mmol), [4-(morpholinomethyl)phenyl]boronic acid hydrochloride (240 mg, 0.93 mmol), potassium phosphate (198 mg, 0.93 mmol) and tetrakis(triphenylphosphine)palladium (0) (16 mg, 0.01 mmol) in DMF/Water 3/1 (4 ml) was heated at 130° C. under microwave irradiation for 30 minutes. The reaction was filtered through Celite™ and solvents were removed under reduced pressure. The resulting residue was taken up in DCM (50 ml) and washed with NaHCO3 saturated aqueous solution (25 ml). The organic layer was separated and dried over MgSO4 before concentration to dryness under reduced pressured. The reaction crude was purified by flash column chromatography using a 12 g silica gel cartridge and eluting with DCM (Solvent A) and MeOH (Solvent B) and the following gradient: 2 min hold 100% A followed by a 18 min ramp to 10% B and then 5 min hold at 10% B. The desired fractions were pooled together and concentrated to dryness under vacuum to obtain the crude material as an off-white solid (100 mg). The product was further purified by mass directed autopreparative HPLC. The fractions containing product were pooled together and freeze dried to obtain the desired material as a white solid (68 mg, 0.14 mmol, Yield 30%).
Reaction SMILES: C(O)(=O)C(O)=O.[F:7][C:8]([F:28])([F:27])[C:9]1[CH:26]=[CH:25][C:12]([O:13][CH:14]2[C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=3[CH2:18][CH2:17][NH:16][CH2:15]2)=[CH:11][CH:10]=1.Cl[CH2:30][C:31]#[N:32].C(=O)(O)[O-].[Na+]>CN(C=O)C>[C:31]([CH2:30][N:16]1[CH2:15][CH:14]([O:13][C:12]2[CH:25]=[CH:26][C:9]([C:8]([F:7])([F:27])[F:28])=[CH:10][CH:11]=2)[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[CH2:18][CH2:17]1)#[N:32]
Reactant: N#CCCl
Reactant: FC(F)(F)c1ccc(OC2CNCCc3ccccc32)cc1
Agent: O=C(O)C(=O)O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Product: N#CCN1CCc2ccccc2C(Oc2ccc(C(F)(F)F)cc2)C1
Temperature: 70 °C

Procedure:
A mixture of 2,3,4,5-tetrahydro-1-(p-trifluoromethylphenoxy)-3-benzazepine of Example 1 (16 g, 0.052 mole), chloroacetonitrile (8 g, 0.10 mole) and sodium bicarbonate (17 g, 0.20 mole) in DMF (125 ml) was warmed at 70° C. for 2.5 hours. The mixture was concentrated to an oil which was stirred with water and extracted with ethyl acetate. The organic extracts were washed twice with water and dried (saturated NaCl, anhydrous MgSO4). After filtering, the solvent was evaporated to an oil (18 g) which solidified upon triturating with petroleum ether to a solid (16.5 g, 92%, m.p. 125°-129° C. A sample was recrystallized from the hexanes to yield 3-cyanomethyl-2,3,4,5-tetrahydro-1-(p-trifluoromethylphenoxy)-3-benzazepine, m.p. 134°-135° C.
Reaction SMILES: [OH2:1].[CH2:2](O)[CH2:3][CH2:4][CH2:5][OH:6]>C1COCC1>[CH3:2][CH2:3][CH2:4][CH2:5][O:1][C@H:4]([CH2:5][OH:6])[CH2:3][CH3:2]
Reactant: OCCCCO
Reactant: O
Solvent: C1CCOC1
Product: CCCCO[C@@H](CC)CO
Reaction time: 4 h

Procedure:
Polymerization was carried out by using the continuous polymerization device as shown in FIG. 3. First, into a 300 ml of polymerization tank 1 having a stirring means and a reflux condenser was charged 200 g of 12-tungstophosphoric acid having a coordinated water number of 3.5 (H3PW12O40.3.5H2O). 150 g of a monomer mixture containing THF and 1.8 wt. % of 1,4-butane diol was added thereto, and the mixture was stirred. By setting the polymerization tank temperature at 60° C., stirring was continued in a nitrogen atmosphere for 4 hours and feeding of a mixture containing THF and 1.8 wt. % of 1,4-butane diol was commenced at the rate of 32 ml/Hr. The reaction was carried out while circulating the liquid from the lower layer in the phase separation tank 2 to the reaction tank and removing the upper layer after phase separation by allowing it to overflow. From the upper layer liquid overflown, unreacted THF was removed by distillation to obtain PTMG. Substantially no unreacted 1,4-butane diol was detected. After continuous running for 100 hours, 850 g of PTMG having a number average molecular weight of 1750 was obtained.
Reaction SMILES: [OH:1][CH2:2][C:3]([C@H:5]([C@@H:7]([C@H:9]([CH2:11]O)[OH:10])O)O)=O.C(OS(C1C=CC=CC=1)(=O)=O)CCCCCCCCCCC.[Na].O.[ClH:37]>[Cl-].C([N+](C)(C)C)CCCCCCCCCCCCCCC.C1(C)C=CC=CC=1>[Cl:37][CH2:11][C:9]1[O:10][C:3]([CH:2]=[O:1])=[CH:5][CH:7]=1
Reactant: O=C(CO)[C@@H](O)[C@H](O)[C@@H](O)CO
Reactant: Cl
Agent: CCCCCCCCCCCCCCCC[N+](C)(C)C
Agent: CCCCCCCCCCCCOS(=O)(=O)c1ccccc1
Agent: [Cl-]
Solvent: O
Solvent: Cc1ccccc1
Product: O=Cc1ccc(CCl)o1

Procedure:
To a three-necked flask equipped with a condenser and a stirrer were added 2.5 g (0.014 mole) of a commercially available L-(-)-sorbose and two kinds of surface active agent, i.e., 47.1 mg (0.00014 mole) of cetyltrimethylammonium chloride and 51.3 mg (0.00014 mole) of sodium laurylbenzenesulfonate. Then, 2.5 ml of water and 15 ml of toluene were added thereto and the mixture was stirred. Thereafter, a molar excess of hydrogen chloride was passed through the mixture at room temperature for about 30 minutes, and the mixture was stirred at room temperature for a further 2.5 hours. The reaction solution was filtered through Celite while being washed with a small amount of a water-toluene mixture. The toluene layer was neutralized, dried and concentrated to obtain about 1.0 g (theoretical yield 2.0 g) of 5-chloromethylfurfural as a crude product.
Reaction SMILES: COC1C=CC(C(C2SC=NN=2)[N:10]2[C:18]3[C:13](=[N:14][CH2:15][NH:16][CH:17]=3)[CH:12]=[C:11]2[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[F:25])=C(C(F)(F)F)C=1.FC1C=CC=CC=1C1NC2C=NC=NC=2C=1.[F:51][C:52]([F:81])([F:80])[C:53]1[CH:58]=[C:57]([C:59]([F:62])([F:61])[F:60])[CH:56]=[CH:55][C:54]=1[C:63]1[CH:67]=[C:66]([CH2:68]OS(C2C=CC(C)=CC=2)(=O)=O)[O:65][N:64]=1>>[F:81][C:52]([F:51])([F:80])[C:53]1[CH:58]=[C:57]([C:59]([F:62])([F:60])[F:61])[CH:56]=[CH:55][C:54]=1[C:63]1[CH:67]=[C:66]([CH2:68][N:16]2[CH:17]=[C:18]3[N:10]=[C:11]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[F:25])[CH:12]=[C:13]3[N:14]=[CH:15]2)[O:65][N:64]=1
Reactant: COc1ccc(C(c2nncs2)n2c(-c3ccccc3F)cc3c2=CNCN=3)c(C(F)(F)F)c1
Reactant: Cc1ccc(S(=O)(=O)OCc2cc(-c3ccc(C(F)(F)F)cc3C(F)(F)F)no2)cc1
Agent: Fc1ccccc1-c1cc2ncncc2[nH]1
Product: Fc1ccccc1-c1cc2ncn(Cc3cc(-c4ccc(C(F)(F)F)cc4C(F)(F)F)no3)cc-2n1
Yield: 7 %

Procedure:
Prepared analogously to the method described for 3-[5[(4-methoxy-2-trifluoromethyl-phenyl)-[1,3,4]thiadiazol-2-ylmethyl]-6-(2-fluorophenyl)-3H-pyrrolo[3,2-d]pyrimidine beginning with 6-(2-fluorophenyl)-5H-pyrrolo[3,2-d]pyrimidine (100 mg, 0.46 mmol) and toluene-4-sulfonic acid 3-(2,4-bis-trifluoromethylphenyl)-isoxazol-5-ylmethyl ester (322 mg, 0.7 mmol) to produce the desired product (16.1 mg, 7%). 1H-NMR: (d6-DMSO, 400 MHz) δ 9.58 (s, 1H), 9.40 (s, 1H), 8.26 (s, 1H), 8.24 (d, 1H), 8.16 (dt, 1H), 7.83 (d, 1H), 7.72 (m, 1H), 7.58 (s, 1H), 7.52 (d, 1H), 7.44 (d, 1H) 7.13 (d, 1H), 6.20 (s, 2H). LCMS calculated for C24H13F7N4O 506.4, found 507.09 (M+H)+.
Reaction SMILES: [OH:1]OS([O-])=O.[K+].[CH2:7]([S:9][C:10]1[C:11]2[N:12]([CH:19]=[C:20]([C:22]3[CH:23]=[N:24][C:25]([O:28][CH3:29])=[CH:26][CH:27]=3)[CH:21]=2)[N:13]=[CH:14][C:15]=1[C:16]([NH2:18])=[O:17])[CH3:8]>O.CC(C)=O>[CH2:7]([S:9]([C:10]1[C:11]2[N:12]([CH:19]=[C:20]([C:22]3[CH:23]=[N:24][C:25]([O:28][CH3:29])=[CH:26][CH:27]=3)[CH:21]=2)[N:13]=[CH:14][C:15]=1[C:16]([NH2:18])=[O:17])=[O:1])[CH3:8]
Reactant: O=S([O-])OO
Reactant: CCSc1c(C(N)=O)cnn2cc(-c3ccc(OC)nc3)cc12
Agent: [K+]
Solvent: O
Solvent: CC(C)=O
Product: CCS(=O)c1c(C(N)=O)cnn2cc(-c3ccc(OC)nc3)cc12
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A solution of oxone (3.30 g, 5.37 mmol) in water (Volume: 40 mL) was added dropwise to a yellow suspension of impure 4-(ethylthio)-6-(6-methoxypyridin-3-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide (0.787 g, 2.441 mmol) in acetone (Ratio: 1.000, Volume: 40 mL) at rt. The resulting suspension was stirred at rt for 3 h. LCMS and HPLC showed that the starting material was consumed and the desired product was formed. The suspension was filtered, washed with water (2×10 mL), and dried under high vacuum to give a green-yellow solid. 1H NMR and HPLC indicated that the desired product was the major component, but the material was impure. The amount of the material is more than theoretical weight and the material is not totally soluble when making NMR solution, indicating the possible presence of inorganic salt. The material was treated with water (10 mL), stirred for 15 min, filtered, washed with H2O (2×5 mL), and dried under high vacuum to give a green-yellow solid (591.3 mg; 44% yield over 2 steps). 1H NMR, LCMS and HPLC indicated that the material was not pure, but the major component is consistent with the desired product. 1 H NMR (400 MHz, DMSO-d6) δ ppm 8.83 (1 H, d, J=1.54 Hz), 8.54 (1H, s), 8.28 (1 H, br. s.), 8.07 (1 H, d, J=1.54 Hz), 8.03 (2H, d, J=8.36 Hz), 7.89 (2 H, d, J=8.36 Hz), 7.80 (1 H, br. s.), 3.31-3.46 (2 7H, m), 1.35 (3 H, t, J=7.48 Hz).
Reaction SMILES: [C:1]([Si:5]([CH3:14])([CH3:13])[O:6][CH2:7][C:8]([CH3:12])([CH3:11])[CH2:9][OH:10])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:22][S:23](Cl)(=[O:25])=[O:24].O>ClCCl>[C:1]([Si:5]([CH3:14])([CH3:13])[O:6][CH2:7][C:8]([CH3:12])([CH3:11])[CH2:9][O:10][S:23]([CH3:22])(=[O:25])=[O:24])([CH3:4])([CH3:3])[CH3:2]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)(CO)CO[Si](C)(C)C(C)(C)C
Solvent: O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(CO[Si](C)(C)C(C)(C)C)COS(C)(=O)=O
Temperature: 0 °C
Reaction time: 2 h
Yield: 87 %

Procedure:
To the solution of 3-(tert-butyl-dimethyl-silanyloxy)-2,2-dimethyl-propan-1-ol (20.4 g, 93 mmol) and triethylamine (26 g, 186 mmol) in dichloromethane (200 mL) at 0° C. was added a dichlormethane solution (20 mL) of methanesulfonyl chloride (Aldrich) (8.69 mL, 112 mmol). The reaction mixture was stirred at 0° C. for 2 h. Water was added. Organic layer was separated, the aqueous layer was extracted with dichlormethane. The combined organic layers were washed with diluted aqueous HCl solution, saturated aqueous NaHCO3 solution, brine, dried over MgSO4, and concentrated to give methanesulfonic acid 3-(tert-butyl-dimethyl-silanyloxy)-2,2-dimethyl-propyl ester as a yellow oil (24 g, 87%).
Reaction SMILES: CN(C)[CH:3]=[O:4].[C:6]([O:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][C:20]1[C:25]([O:26]C2CCCCO2)=[C:24]([O:33][CH3:34])[C:23]([O:35][CH3:36])=[CH:22][C:21]=1C)(=[O:8])[CH3:7]>O=O.C1C=C(C=NCCN=CC2C([O-])=CC=CC=2)C([O-])=CC=1.[Co+2]>[C:6]([O:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][C:20]1[C:25](=[O:26])[C:24]([O:33][CH3:34])=[C:23]([O:35][CH3:36])[C:3](=[O:4])[C:21]=1[CH3:22])(=[O:8])[CH3:7]
Reactant: COc1cc(C)c(CCCCCCCCCCOC(C)=O)c(OC2CCCCO2)c1OC
Reactant: CN(C)C=O
Agent: [Co+2]
Agent: O=O
Agent: [O-]c1ccccc1C=NCCN=Cc1ccccc1[O-]
Product: COC1=C(OC)C(=O)C(CCCCCCCCCCOC(C)=O)=C(C)C1=O

Procedure:
To a dimethylformamide solution (20 ml) of 6-(10-acetoxydecyl)-2,3-dimethoxy-5-methyl-1-tetrahydropyranyloxybenzene (240 mg) is added bis(salicylidene)ethylenediiminocobalt(II) (14 mg), followed by stirring in oxygen streams at atmospheric temperature and pressure for 72 hours. The reaction product is isolated in the same manner as Example 7 and recrystallized from hexane. The above procedure yields 6-(10-acetoxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (110 mg) as orange-yellow needles melting at 37° C.-38° C.