Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([Li])CCC.[CH3:6][O:7][P:8]([CH3:12])(=[O:11])[O:9][CH3:10].C([O:15][C:16](=O)[CH:17]([CH3:23])[CH2:18][CH:19]=[C:20]([CH3:22])[CH3:21])C.C(O)(=O)C>CCCCCC.O1CCCC1>[CH3:6][O:7][P:8]([CH2:12][C:16]([CH:17]([CH3:23])[CH2:18][CH:19]=[C:20]([CH3:22])[CH3:21])=[O:15])(=[O:11])[O:9][CH3:10]
Reactant: CCOC(=O)C(C)CC=C(C)C
Reactant: COP(C)(=O)OC
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: CCCCCC
Product: COP(=O)(CC(=O)C(C)CC=C(C)C)OC
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 64.4 %

Procedure:
Under argon at -60° C., 274.7 ml of a 1.61-molar butyllithium solution in hexane was added dropwise to a solution of 59 g of methanephosphonic acid dimethyl ester in 400 ml of absolute tetrahydrofuran. After 15 minutes of agitation, a solution of 34.05 g of 2,5-dimethyl-4-hexenoic acid ethyl ester in 100 ml of absolute tetrahydrofuran was added dropwise thereto. The reaction mixture was allowed to warm up to room temperature within 4 hours and thereafter stirred for another 3 hours. Then the mixture was combined with 26.5 ml of glacial acetic acid and concentrated under vacuum. The residue was taken up in ether/water, the aqueous phase was combined with solid sodium chloride, and shaken out with ether. The combined organic phases were dried over magnesium sulfate and concentrated on a forced circulation evaporator. The evaporation residue was purified by column chromatography on silica gel with hexane/50-100% ethyl acetate as the mobile phase, thus producing 32 g of the desired compound.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:19]3[C:14]([CH:15]=[N:16][C:17]([S:20][CH3:21])=[N:18]3)=[C:13]([CH3:22])[CH:12]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].C(Cl)Cl.C1C=C(Cl)C=C(C(OO)=[O:34])C=1>>[CH3:21][S:20]([C:17]1[N:16]=[CH:15][C:14]2=[C:13]([CH3:22])[CH:12]=[C:11]([C:8]3[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:10][CH:9]=3)[N:19]2[N:18]=1)=[O:34]
Reactant: CSc1ncc2c(C)cc(-c3ccc(S(C)(=O)=O)cc3)n2n1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: Cc1cc(-c2ccc(S(C)(=O)=O)cc2)n2nc(S(C)=O)ncc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 73.4 %

Procedure:
Into a 30 mL vial, [A] 7-(4-Methanesulfonyl-phenyl)-5-methyl-2-methylsulfanyl-pyrrolo[2,1-f][1,2,4]triazine (0.260 g, 0.000780 mol) and Methylene chloride (20 mL, 0.3 mol) were added. m-CPBA 70-75% (70:30, m-Chloroperbenzoic acid:3-Chlorobenzoic acid, 0.211 g, 0.000858 mol) was added and stirred at room temperature overnight. The reaction was partitioned with DCM and saturated NaHCO3. The organic was separated and washed with water then Brine and dried over Na2SO4. The solid was filtered and washed with DCM. The organic was removed under vacuum to give a solid. The solid was triturated with Et2O and filtered to give 2-Methanesulfinyl-7-(4-methanesulfonyl-phenyl)-5-methyl-pyrrolo[2,1-f][1,2,4]triazine as a yellow solid (0.20 g, 73%) NMR 1H (CDCl3-d)-8.99 (s, 1H), 8.24 (d, 2H, J=8.45 Hz), 8.08 (d, 2H, J=8.40 Hz), 7.28 (s, 1H), 3.10 (s, 3H), 3.02 (bs, 4H), 2.54 (s, 3H)
Reaction SMILES: [Br:1][C:2]1[N:6]([CH3:7])[N:5]=[CH:4][C:3]=1[C:8](=O)[CH2:9][N:10]([CH:16]=O)[NH:11][C:12]([O:14][CH3:15])=[O:13].C([O-])(=O)C.[NH4+].C([NH2:26])=O.C(#N)C>O>[CH3:15][O:14][C:12](=[O:13])[NH:11][N:10]1[CH:9]=[C:8]([C:3]2[CH:4]=[N:5][N:6]([CH3:7])[C:2]=2[Br:1])[N:26]=[CH:16]1
Reactant: COC(=O)NN(C=O)CC(=O)c1cnn(C)c1Br
Reactant: NC=O
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: O
Solvent: CC#N
Product: COC(=O)Nn1cnc(-c2cnn(C)c2Br)c1
Temperature: 130 °C
Reaction time: 0.17 h

Procedure:
Methyl 2-[2-(5-bromo-1-methyl-1H-pyrazol-4-yl)-2-oxoethyl]-2-formylhydrazine carboxylate (1.20 g, 3.76 mmol) was mixed with ammonium acetate (1.16 g, 15.0 mmol), formamide (4 mL) and acetonitrile (5 mL). The reaction was heated to 130° C., and the acetonitrile was allowed to boil off for 10 minutes. Heating was continued for an additional 4 hours. After addition of water, the crude mixture was extracted eight times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo; purification via silica gel chromatography (Gradient: 0% to 100% [10% methanol in ethyl acetate] in heptane) afforded the product as a pinkish solid. Yield: 800 mg, 2.67 mmol, 19% over two steps. LCMS m/z 299.8 (M+1). 1H NMR (400 MHz, CD3OD) δ 3.80 (br s, 3H), 3.90 (s, 3H), 7.52 (d, J=1.3 Hz, 1H), 7.77 (d, J=1.3 Hz, 1H), 7.85 (s, 1H).
Reaction SMILES: O[CH2:2][CH2:3][C:4]1[CH:23]=[CH:22][C:7]([O:8][CH2:9][CH2:10][O:11][CH2:12][CH2:13][NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:6][CH:5]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)(Cl)(Cl)[Cl:44]>>[Cl:44][CH2:2][CH2:3][C:4]1[CH:23]=[CH:22][C:7]([O:8][CH2:9][CH2:10][O:11][CH2:12][CH2:13][NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:6][CH:5]=1
Reactant: CC(C)(C)OC(=O)NCCOCCOc1ccc(CCO)cc1
Reactant: ClC(Cl)(Cl)Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: CC(C)(C)OC(=O)NCCOCCOc1ccc(CCCl)cc1

Procedure:
To tert-butyl 2-{2-[4-(2-hydroxyethyl)phenoxy]ethoxy}ethylcarbamate (0.56 g, 1.7 mmol) dissolved in 10 ml carbon tetrachloride was added triphenylphosphine bound on styrene (861 mg, 2.6 mmol of about 3 mmol/g resin). The reaction mixture was heated to reflux for 2 hours. After the required time the reaction was cooled and filtered. After drying a quantitative yield of product was isolated. 1H NMR (CDCl3) δ 7.11 (d, 2H, Ar), 6.86 (d, 2H, Ar), 4.95 (bs, exchangeable, NH), 4.08 (dd, CH2—O), 3.79 (dd, CH2—O), 3.65 (t, CH2—Cl), 3.59 (t, CH2—O), 3.32 (bm, CH2—NH), 2.99 (t, CH2—Ar), 1.70 (bs, exchangeable, OH) 1.42 (s, 9H, CH3). Mass spectrum, m/e Calcd for C17H27ClNO4+: 344.16 (100%), 346.16 (32%). Found: 344.57, 346.55.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:15]=[CH:14][C:10]([C:11](O)=O)=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.[NH2:16][N:17]1[C:21]([C:22]2[CH:27]=[C:26]([O:28][CH3:29])[C:25]([O:30][CH3:31])=[C:24]([O:32][CH3:33])[CH:23]=2)=[N:20][N:19]=[C:18]1[SH:34]>O=P(Cl)(Cl)Cl>[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[CH:15]=[CH:14][C:10]([C:11]3[S:34][C:18]4=[N:19][N:20]=[C:21]([C:22]5[CH:27]=[C:26]([O:28][CH3:29])[C:25]([O:30][CH3:31])=[C:24]([O:32][CH3:33])[CH:23]=5)[N:17]4[N:16]=3)=[CH:9][CH:8]=2)[CH2:3][CH2:2]1
Reactant: COc1cc(-c2nnc(S)n2N)cc(OC)c1OC
Reactant: O=C(O)c1ccc(N2CCOCC2)cc1
Solvent: O=P(Cl)(Cl)Cl
Product: COc1cc(-c2nnc3sc(-c4ccc(N5CCOCC5)cc4)nn23)cc(OC)c1OC
Temperature: 25 °C
Yield: 24.4 %

Procedure:
A mixture of 4-morpholinobenzoic acid (86 mg, 0.42 mmol) and 4-amino-3-mercapto-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazole (102 mg, 0.36 mmol) was refluxed in POCl3 (5 mL) for 2 h. The reaction mixture was cooled to room temperature and excess POCl3 was removed under vacuum. The residue was dissolved in ethyl acetate and washed with saturated NaHCO3. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The crude product was purified by chromatography (80% ethyl acetate/hexane; 1 mL methanol/100 mL of solvent) to give the title compound as a yellow solid (40 mg, 0.088 mmol, 24%). 1H NMR (CDCl3): 7.78 (m, 2H), 7.73 (s, 2H), 6.98 (m, 2H), 4.00 (s, 6H), 3.94 (s, 3H), 3.89 (m, 4H), 3.41 (m, 4H).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([C:8]2[S:9][CH:10]=[CH:11][CH:12]=2)[CH:5]=[CH:4][C:3]=1[NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17].Cl[C:22]([O:24][CH2:25][CH3:26])=[O:23]>ClCCl.CN(C1C=CN=CC=1)C.O>[S:9]1[CH:10]=[CH:11][CH:12]=[C:8]1[C:6]1[CH:5]=[CH:4][C:3]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[C:2]([NH:1][C:22](=[O:23])[O:24][CH2:25][CH3:26])[CH:7]=1
Reactant: CC(C)(C)OC(=O)Nc1ccc(-c2cccs2)cc1N
Reactant: CCOC(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: O
Product: CCOC(=O)Nc1cc(-c2cccs2)ccc1NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 16 h
Yield: 44 %

Procedure:
To a solution of tert-butyl (2-amino-4-(thiophen-2-yl)phenyl)carbamate (0.20 g, 0.69 mmol, 1.0 equiv.) in dichloromethane (4 mL) was added ethyl chloroformate (0.08 mL, 0.83 mmol, 1.2 equiv.), TEA (0.19 mL, 1.37 mmol, 2.0 equiv.) and DMAP (8 mg, 0.07 mmol, 0.1 equiv.) at 0° C. The reaction was warmed to room temperature and stirred for 16 h. The reaction was then diluted with dichloromethane and water. The organic layer was separated, washed with water and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified on column chromatography (silica gel, 20% EtOAc/hexanes) to give tert-butyl ethyl (4-(thiophen-2-yl)-1,2-phenylene)dicarbamate (0.11 g, 44% yield).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([CH3:8])[NH:5][C:4]2=[CH:9][C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[N:11][C:3]=12.[CH3:18][C:19]1[O:23][C:22]([CH2:24][NH2:25])=[CH:21][CH:20]=1.C([O-])([O-])=O.[K+].[K+].C(Cl)Cl>O>[CH3:18][C:19]1[O:23][C:22]([CH2:24][NH:25][C:2]2[N:7]=[C:6]([CH3:8])[NH:5][C:4]3[C:3]=2[N:11]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:9]=3)=[CH:21][CH:20]=1
Reactant: Cc1nc(Cl)c2nc(-c3ccccc3)cc-2[nH]1
Reactant: Cc1ccc(CN)o1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: ClCCl
Product: Cc1nc(NCc2ccc(C)o2)c2nc(-c3ccccc3)cc-2[nH]1
Temperature: 140 °C
Reaction time: 2.5 h
Yield: 61.2 %

Procedure:
To a mixture of 4-chloro-2-methyl-6-phenylpyrrolo[3,2-d]pyrimidine (Example 1(e)) (47.6 mg, 0.19 mmol) and 5-methyl-2-furanmethanamine (Acros Chemical Company) (100 μL, 0.98 mmol) was added a solution of K2CO3 (0.11 g, 0.76 mmol) in H2O (1.5 mL). This mixture was stirred at 140° C. in a closed-capped Wheaton vial for 2.5 h. After cooling, CH2Cl2 (10 mL) and H2O (10 mL) were added. The organic solution was removed and the aqueous solution washed with CH2Cl2 (10 mL). The combined organic solutions were washed with saturated NaCl (15 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (3% MeOH:CHCl3 on silica gel) to give 37 mg (62%) of the title compound as a beige solid. Mp: 125-127.5° C. MS m/z: 319 (M+1), 294, 225, 195, 147. 1H NMR (CD3OD, 400 MHz): δ 2.28 (s, 3), 2.53 (s, 3), 4.72 (s, 2), 5.97 (d, 1, J=3.0), 6.24 (d, 1, J=3.0), 6.66 (s, 1), 7.34 (m, 1), 7.43 (t, 2, J=7.7), 7.71 (dd, 2, J=7.1, 1.4). HRMS: Calcd for M+H, C19H18ON4: 319.1555. Found: 319.1566.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:11])[CH3:10])=[C:4]([F:12])[C:3]=1[CH2:13][OH:14].[CH3:15][S:16](Cl)(=[O:18])=[O:17]>C(Cl)Cl>[CH3:15][S:16]([O:14][CH2:13][C:3]1[C:2]([Cl:1])=[CH:7][CH:6]=[C:5]([NH:8][C:9](=[O:11])[CH3:10])[C:4]=1[F:12])(=[O:18])=[O:17]
Reactant: CS(=O)(=O)Cl
Reactant: CC(=O)Nc1ccc(Cl)c(CO)c1F
Solvent: ClCCl
Product: CC(=O)Nc1ccc(Cl)c(COS(C)(=O)=O)c1F
Temperature: 25 °C
Reaction time: 2 h
Yield: 91.9 %

Procedure:
A 0° C. of N-(4-chloro-2-fluoro-3-(hydroxymethyl)phenyl)acetamide (1.05 g, 4.82 mmol) and TEA (1.003 mL, 7.24 mmol) in DCM (30 mL) was treated slowly with methanesulfonyl chloride (0.414 mL, 5.31 mmol), warmed to RT and stirred for 2 h. The mixture was treated with satd. NaHCO3, extracted with DCM (2×) and the combined organics were washed with brine, dried over Na2SO4 and concentrated to dryness to afford 3-acetamido-6-chloro-2-fluorobenzyl methanesulfonate (1.31 g, 74% yield) as an off-white solid. MS (ESI) m/z: 296.0 [M+H]+.
Reaction SMILES: [OH:1][CH:2]([C:4]1[S:8][C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)=[N:6][N:5]=1)[CH3:3].C(N(CC)CC)C.[CH3:22][S:23](Cl)(=[O:25])=[O:24]>ClCCl>[CH3:22][S:23]([O:1][CH:2]([C:4]1[S:8][C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)=[N:6][N:5]=1)[CH3:3])(=[O:25])=[O:24]
Reactant: CS(=O)(=O)Cl
Reactant: CC(O)c1nnc(-c2ccccn2)s1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(OS(C)(=O)=O)c1nnc(-c2ccccn2)s1
Reaction time: 1 h

Procedure:
To a mixture of (RS)-2-(5-(1-hydroxy-ethyl)-1,3,4-thiadiazol-2-yl)-pyridine (1.0 gm), and triethylamine (2 ml) in dichloromethane (50 ml) was added methanesulfonyl chloride (0.9 gm) at −10° C. The reaction mixture was stirred over a period of 1 h. The reaction was quenched by addition of water and layers were separated. Aqueous layer was extracted with dichloromethane. Combined organic layer was washed with aqueous sodium bicarbonate followed by water and evaporated under vacuum to provide the title compound in 1.0 gm quantity (73%) as an oil.
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([N:10]2[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][C:18]3[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=3[NH2:25])[CH2:12][CH2:11]2)=[N:2]1.[C:26](Cl)(=[O:28])[CH3:27]>>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[C:3]([N:10]2[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][C:18]3[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=3[NH:25][C:26](=[O:28])[CH3:27])[CH2:12][CH2:11]2)=[N:2]1
Reactant: CC(=O)Cl
Reactant: Nc1ccc(F)cc1CCN1CCN(c2nsc3ccccc23)CC1
Product: CC(=O)Nc1ccc(F)cc1CCN1CCN(c2nsc3ccccc23)CC1
Yield: 25.7 %

Procedure:
Starting from 2-[2-(4-1,2-benzisothiazol-3-yl-piperazin-1-yl)-ethyl]-4-fluoro-phenylamine (142 mg, 0.4 mmol) and acetyl chloride (32.7 μL, 0.4 mmol) and following the procedure as outlined in Example 1, 41 mg of N-{2-[2-(4-1,2-benzisothiazol-3-yl-piperazin-1-yl)-ethyl]-4-fluoro-phenyl}-acetamide was isolated as a yellow foam in 100% purity @ 254 nm; LCMS (APCI): 399 [M+H]+.
Reaction SMILES: [N+]([O-])([O-])=O.[N+]([O-])(O)=O.[N+]([O-])(O)=O.[N+]([O-])([O-])=O.[N+]([O-])([O-])=O.[N+]([O-])([O-])=O.[NH4+].[NH4+].[NH4+].[NH4+].C[O:30][C:31]1[C:36]2[CH:37]=[CH:38][O:39][C:35]=2[C:34]([O:40]C)=[C:33]([O:42][CH2:43][N:44]2[C:54](=[O:55])[C:53]3[C:48](=[CH:49][C:50]([O:59][CH3:60])=[CH:51][C:52]=3[CH:56]([CH3:58])[CH3:57])[S:45]2(=[O:47])=[O:46])[C:32]=1[C:61](=[O:63])[CH3:62]>O.C(#N)C>[C:61]([C:32]1[C:31](=[O:30])[C:36]2[CH:37]=[CH:38][O:39][C:35]=2[C:34](=[O:40])[C:33]=1[O:42][CH2:43][N:44]1[C:54](=[O:55])[C:53]2[C:48](=[CH:49][C:50]([O:59][CH3:60])=[CH:51][C:52]=2[CH:56]([CH3:58])[CH3:57])[S:45]1(=[O:47])=[O:46])(=[O:63])[CH3:62]
Reactant: COc1cc(C(C)C)c2c(c1)S(=O)(=O)N(COc1c(C(C)=O)c(OC)c3ccoc3c1OC)C2=O
Agent: O=[N+]([O-])[O-]
Agent: [NH4+]
Solvent: O=[N+]([O-])O
Solvent: O
Solvent: CC#N
Product: COc1cc(C(C)C)c2c(c1)S(=O)(=O)N(COC1=C(C(C)=O)C(=O)c3ccoc3C1=O)C2=O
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 46.1 %

Procedure:
A solution of triceric tetraammonium hexanitrate (0.98 g) in water (3 mL) was added dropwise to a solution of 2-(4,7-dimethoxy-5-acetylbenzofuran-6-yl)oxymethyl-4-isopropyl-6-methoxysaccharin (0.3 g) in acetonitrile (5 mL). The mixture was stirred at room temperature for 15 minutes and poured into ice-water. The resulting gold colored solid was purified by rapid chromatography on silica gel with dichloromethane-ether (95:5) as eluant and crystallization with sonication from ethanol affording 2-(5-acetyl-4,7-dihydro-4,7-dioxobenzofuran-6-yl)oxymethyl-4-isopropyl-6-methoxysaccharin (0.13 g, 46.6% yield, m.r. 193°-195° C. with decomposition).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]2[N:9]=[C:10]([C:12](=[S:14])[NH2:13])[S:11][C:7]=2[C:6]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)=[CH:5][CH:4]=1.[I:21][CH3:22]>O1CCCC1>[IH:21].[CH3:22][S:14][C:12]([C:10]1[S:11][C:7]2[C:6]([N:15]3[CH2:16][CH2:17][O:18][CH2:19][CH2:20]3)=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[C:8]=2[N:9]=1)=[NH:13]
Reactant: CI
Reactant: COc1ccc(N2CCOCC2)c2sc(C(N)=S)nc12
Solvent: C1CCOC1
Product: COc1ccc(N2CCOCC2)c2sc(C(=N)SC)nc12
Product: I
Temperature: 25 °C
Reaction time: 72 h
Yield: 51 %

Procedure:
g 4-Methoxy-7-morpholin-4-yl-benzothiazole-2-carbothioic acid amide and 20.3 ml iodomethane in 100 ml tetrahydrofurane were stirred at room temperature for three days. The resulting precipitate was filtered to yield 0.74 g (51%) 4-methoxy-7-morpholin-4-yl-benzothiazole-2-carboximidothioic acid methyl ester hydroiodide; M.p.: 169–171° C.; MS (ISP): m/e=324 (M+H+).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N:4][C:5](=[O:8])[NH:6][CH:7]=1.Br[CH2:10][C:11]([C:13]1[CH:18]=[CH:17][C:16]([S:19]([CH3:21])=[O:20])=[CH:15][CH:14]=1)=[O:12]>C(N(CC)CC)C.C(O)C>[Cl:1][C:2]1[CH:3]=[N:4][C:5](=[O:8])[N:6]([CH2:10][C:11]([C:13]2[CH:18]=[CH:17][C:16]([S:19]([CH3:21])=[O:20])=[CH:15][CH:14]=2)=[O:12])[CH:7]=1
Reactant: CS(=O)c1ccc(C(=O)CBr)cc1
Reactant: O=c1ncc(Cl)c[nH]1
Solvent: CCN(CC)CC
Solvent: CCO
Product: CS(=O)c1ccc(C(=O)Cn2cc(Cl)cnc2=O)cc1
Yield: 54.6 %

Procedure:
A suspension of 5-chloropyrimidin-2-one (399 mg). and 2-bromo-4'-methylsulphinylacetophenone (784 mg) in triethylamine (1 ml) and ethanol (20 ml) was stirred at ambient temperature for one hour, when the resulting suspension was chilled in ice. The collected solid was crystallised from ethanol to give the title pyrimidinone (509 mg,); m.p. 219°-220°; λmaxEtOH 233.5 nm (ε 17920), 332 nm (ε 2060), λinf 266 nm (ε 9280).
Reaction SMILES: FC(F)(F)S(O)(=O)=[O:4].C[C:10]#[C:11][CH:12]=[CH:13][C:14]#[C:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH:21]=[O:22].[C:23]([O-:26])(O)=O.[Na+]>C(Cl)Cl>[OH:4][C:16]12[C:21](=[O:22])[CH:20]([CH2:19][CH2:18][CH2:17]1)[CH:23]([OH:26])[C:10]#[C:11][CH:12]=[CH:13][C:14]#[C:15]2
Reactant: O=S(=O)(O)C(F)(F)F
Reactant: CC#CC=CC#CCCCCCC=O
Reactant: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: O=C1C2CCCC1(O)C#CC=CC#CC2O
Reaction time: 0.17 h

Procedure:
Trifluoromethane sulfonic acid (16 ul) was added in one portion to a solution of 65 mg 8-hydroxy-1-TBSoxybicyclo[7.3.1]trideca-4-ene-2,6-diyne-13-one in 20 mL of CH2Cl2 stirring over 1 g of 2A molecular sieves at 25°. The reaction was stirred for 10min and then poured into 10 %aq NaHCO3 and CH2Cl2. The mixture was extracted and the organic extracts were dried over sodium sulfate. Filtration, concentration, and purification by flash chromotography over silica gel using 1:1 diethyl ether/hexane as eluent provided 26mg of the desired 1,8-dihydroxy-bicyclo[7.3.1]trideca-4-ene-2,6-diyne-13-one:
Reaction SMILES: N1C=CC=CC=1.[CH3:7][O:8][C:9]1[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=1[CH2:11][CH2:12][NH2:13].[CH3:18][S:19](Cl)(=[O:21])=[O:20].O>C(Cl)Cl>[CH3:7][O:8][C:9]1[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=1[CH2:11][CH2:12][NH:13][S:19]([CH3:18])(=[O:21])=[O:20]
Reactant: COc1ccccc1CCN
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: O
Solvent: c1ccncc1
Product: COc1ccccc1CCNS(C)(=O)=O
Temperature: 0 °C
Reaction time: 2 h
Yield: 80.7 %

Procedure:
Pyridine (12.0 mL, 150 mmol) was added to a solution of 2-methoxyphenethylamine (15.1 g, 100 mmol) in CH2Cl2 (100 mL). The reaction was cooled to 0° C. and methanesulfonyl chloride (12.6 g, 110 mmol) was added. The reaction was stirred at 0° C. for 0.5 h and at room temperature for 2 h. Water was added and the aqueous layer was extracted with CH2Cl2 (2×). The organic solution was washed water (1×) and brine (1×), dried over MgSO4, filtered and concentrated to afford N-[2-(2-methoxy-phenyl)-ethyl]-methanesulfonamide (18.5 g).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][N:8]=2)[C:3]([CH:10]=O)=[CH:2]1.[O:12]=[C:13]1[CH2:17][O:16][C:15]([NH:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[C:14]1[C:25]([O:27][CH2:28][CH3:29])=[O:26].N1CCCCC1>C(O)C>[NH:1]1[C:9]2=[N:8][CH:7]=[CH:6][CH:5]=[C:4]2[C:3]([CH:10]=[C:17]2[O:16][C:15]([NH:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[C:14]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[C:13]2=[O:12])=[CH:2]1
Reactant: O=Cc1c[nH]c2ncccc12
Reactant: CCOC(=O)C1=C(Nc2ccccc2)OCC1=O
Solvent: CCO
Solvent: C1CCNCC1
Product: CCOC(=O)C1=C(Nc2ccccc2)OC(=Cc2c[nH]c3ncccc23)C1=O
Temperature: 25 °C
Yield: 49.5 %

Procedure:
To a solution of 7-azaindole-3-carboxaldehyde (0.10 g, 0.70 mmol) and ethyl 4-oxo-2-(phenylamino)-4,5-dihydrofuran-3-carboxylate (0.18 g, 0.70 mmol) in ethanol (3.0 mL), piperidine (0.083 mL, 0.84 mmol) was added at ambient temperature. The mixture was refluxed for 12 h. Cooled to ambient temperature, the precipitate was collected by filtration, washed with cold ethanol and isopropyl ether then dried to afford the titled compound (0.13 g, y. 48%).
Reaction SMILES: [OH-].[Na+].[SH2:3].C1C=CC2C(C3C=CC(O)=CC=3)(C3C=CC(O)=CC=3)OC(=O)C=2C=1.[I:28][C:29]1[CH:37]=[CH:36][CH:35]=[CH:34][C:30]=1[C:31](Cl)=[O:32]>O>[I:28][C:29]1[CH:37]=[CH:36][CH:35]=[CH:34][C:30]=1[C:31]([OH:32])=[S:3]
Reactant: O=C(Cl)c1ccccc1I
Reactant: S
Agent: O=C1OC(c2ccc(O)cc2)(c2ccc(O)cc2)c2ccccc21
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: OC(=S)c1ccccc1I
Reaction time: 4 h

Procedure:
A solution of sodium hydroxide (10.68 g) in water (14 ml) and alcohol (55 ml) was stirred and treated with hydrogen sulphide at 20° until the mixture did not give an immediate alkaline reaction with phenolphthalein. The solution was cooled to 10°-15° and treated slowly with o-iodobenzoyl chloride (33.66 g). The mixture was stirred for 11/4 hours. The precipitated sodium chloride was filtered off and washed with ethanol (25 ml.) The filtrate was concentrated slightly in vacuo and treated with cold water (80 ml). The solution was covered with ether (100 ml) and stirred while the pH was adjusted to 1.3 with 2N-hydrochloric acid. The ether layer was separated and the aqueous layer was further extracted with ether. The combined ether extracts were washed with water and dried. The ether solution was mixed with water and adjusted to pH 7 with dilute sodium hydroxide solution. The aqueous layer was separated, swirled briefly in vacuo and freeze dried. Trituration of the freeze dried product with ether gave the title compound (28.6 g) as a pale yellow solid. νmax. (Nujol) 15.32 cm-1 (COS-).
Reaction SMILES: [CH2:1]([C:7]1[CH:12]=[CH:11][C:10]([C:13]2[C:14]([C:33]#[N:34])=[N:15][N:16]([C:22]([CH3:32])([CH3:31])[CH2:23][C:24]3[CH:29]=[CH:28][C:27]([CH3:30])=[CH:26][CH:25]=3)[C:17]=2[O:18]COC)=[CH:9][CH:8]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].Cl.O1CCOCC1>O1CCCC1.CO>[CH2:1]([C:7]1[CH:8]=[CH:9][C:10]([C:13]2[C:14]([C:33]#[N:34])=[N:15][N:16]([C:22]([CH3:32])([CH3:31])[CH2:23][C:24]3[CH:25]=[CH:26][C:27]([CH3:30])=[CH:28][CH:29]=3)[C:17]=2[OH:18])=[CH:11][CH:12]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CCCCCCc1ccc(-c2c(C#N)nn(C(C)(C)Cc3ccc(C)cc3)c2OCOC)cc1
Agent: Cl
Solvent: CO
Solvent: C1COCCO1
Solvent: C1CCOC1
Product: CCCCCCc1ccc(-c2c(C#N)nn(C(C)(C)Cc3ccc(C)cc3)c2O)cc1
Temperature: 25 °C
Reaction time: 14 h
Yield: 36.6 %

Procedure:
266 mg of 4-(4-hexylphenyl)-5-(methoxymethoxy)-1-(2-methyl-1-(p-tolyl)propan-2-yl)-1H-pyrazole-3-carbonitrile was dissolved in 4 mL of tetrahydrofuran and 0.8 mL of methanol, mixed with 4 M hydrochloric acid in dioxane (0.70 mL, 2.8 mmol) and stirred at room temperature for 14 hours. After completion of the reaction, the solvent was partly distilled off under reduced pressure, and the crystals precipitated in the reaction mixture were separated by filtration and washed with isopropyl ether. The filtrate was combined with the isopropyl ether washing and concentrated under reduced pressure, and the resulting residue was purified by intermediate pressure silica gel column chromatography (silica gel 10 g, ethyl acetate:hexane=0:100 to 20:80) to give 88.1 mg of the desired product as a white solid.
Reaction SMILES: [C:1]1([NH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH2:7].[C:9](O)(=O)C.[C:13]([O:16][CH2:17][CH3:18])(=O)C>C([O-])([O-])([O-])OCCC>[CH2:17]([O:16][C:13]1[NH:7][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=2[N:8]=1)[CH2:18][CH3:9]
Reactant: CCOC(C)=O
Reactant: Nc1ccccc1N
Reactant: CC(=O)O
Agent: CCCOC([O-])([O-])[O-]
Product: CCCOc1nc2ccccc2[nH]1
Temperature: 80 °C

Procedure:
To a solution of o-phenylenediamine (2 g) in propyl orthocarbonate (5 ml) was added acetic acid (1.1 ml) and the solution was stirred at 80° C. for 3 Hours. To the reaction mixture was added ethyl acetate, and the solution was washed with an aqueous solution of sodium hydrogen carbonate and water, then dried (Na2SO4), followed by concentration to dryness. The concentrate was purified by column chromatography on silica gel to give crystals. Recrystallization from ethyl acetate-benzene afforded colorless crystals (1.54 g, 47%), m.p. 163-164° C.