Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [S:1]1[C:5]2=[CH:6][N:7]=[CH:8][CH:9]=[C:4]2[CH:3]=[CH:2]1.C([Li])CCC.[CH3:15][Sn:16](Cl)([CH3:18])[CH3:17]>C1COCC1>[CH3:15][Sn:16]([CH3:18])([CH3:17])[C:2]1[S:1][C:5]2=[CH:6][N:7]=[CH:8][CH:9]=[C:4]2[CH:3]=1
Reactant: c1cc2ccsc2cn1
Reactant: C[Sn](C)(C)Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: C[Sn](C)(C)c1cc2ccncc2s1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 71.4 %

Procedure:
A solution of thieno[2,3-c]pyridine (J. Wikel, et al., J. Heterocycl. Chem., 1993, 30, 289) (2.0 g, 14.8 mmol) in THF (50 mL) at −78° C. was treated with n-butyllithium (2.5 M solution in hexane, 7.1 mL, 17.8 mmol), warmed to 0° C., stirred for 15 minutes, cooled to −78° C., treated slowly with trimethyltin chloride (3.54 g, 17.8 mmol) in THF (10 mL), warmed to room temperature for 2 hours, and partitioned between ethyl acetate and brine. The ethyl acetate solution was washed with water, and concentrated. The residue was purified by flash chromatography (10-35% ethyl acetate in hexane) to provide the desired product (3.15 g, 71%). MS (APCI) m/e 298 (M+H)+.
Reaction SMILES: [NH2:1][CH2:2][C@H:3]1[C@@H:8]([CH3:9])[CH2:7][CH2:6][CH2:5][N:4]1[C:10]([C:12]1[N:13]=[C:14]([CH3:24])[S:15][C:16]=1[C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1)=[O:11].[Cl:25][C:26]1[N:31]=[C:30](Cl)[CH:29]=[CH:28][N:27]=1.C([O-])([O-])=O.[K+].[K+]>CC(N(C)C)=O>[Cl:25][C:26]1[N:31]=[C:30]([NH:1][CH2:2][C@H:3]2[C@@H:8]([CH3:9])[CH2:7][CH2:6][CH2:5][N:4]2[C:10]([C:12]2[N:13]=[C:14]([CH3:24])[S:15][C:16]=2[C:17]2[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=2)=[O:11])[CH:29]=[CH:28][N:27]=1
Reactant: Clc1ccnc(Cl)n1
Reactant: Cc1nc(C(=O)N2CCC[C@H](C)[C@@H]2CN)c(-c2ccc(F)cc2)s1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Product: Cc1nc(C(=O)N2CCC[C@H](C)[C@@H]2CNc2ccnc(Cl)n2)c(-c2ccc(F)cc2)s1
Temperature: 120 °C
Reaction time: 18 h

Procedure:
A mixture of rac-cis-(2-(aminomethyl)-3-methylpiperidin-1-yl)(5-(4-fluorophenyl)-2-methylthiazol-4-yl)methanone, 2,4-dichloropyrimidine, and K2CO3 in DMAC was stirred at 120° C. for 18 h. The reaction was cooled and concentrated in vacuo. The crude reaction mixture was purified by reverse-phase preparative HPLC to afford the title compound as the major isomer. MS (ESI) 459.94 (M+H).
Reaction SMILES: [CH2:1]([Mg]Cl)[CH2:2][CH2:3][CH3:4].[CH3:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([S:15]([CH2:18][CH2:19][CH:20]=[O:21])(=[O:17])=[O:16])=[CH:11][CH:10]=1.[Cl-].[NH4+].C(OCC)(=O)C>C1COCC1.O>[CH3:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([S:15]([CH2:18][CH2:19][CH:20]([OH:21])[CH2:1][CH2:2][CH2:3][CH3:4])(=[O:16])=[O:17])=[CH:13][CH:14]=1
Reactant: COc1ccc(S(=O)(=O)CCC=O)cc1
Reactant: CCCC[Mg]Cl
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: C1CCOC1
Product: CCCCC(O)CCS(=O)(=O)c1ccc(OC)cc1
Reaction time: 3 h

Procedure:
Part B: To 22.3 mL (4.3 g, 37 mM) of a 2.0 M butylmagnesium chloride solution in THF at zero° C., was added 4.1 g (18 mmol) of 3-[(4-methoxyphenyl)sulfonyl]propan-1-al from Part A in 30 mL of THF. After 3 hours, the reaction mixture was cooled to zero° C. and 40 mL of saturated ammonium chloride solution was added, followed by ethyl acetate and water, the organic layer was separated and washed with 5% potassium hydrogen sulfate solution, saturated sodium bicarbonate solution and brine, dried with magnesium sulfate, filtered and concentrated to afford 4.7 grams of crude product. This was chromatographed on silica gel using 30%-40% ethyl acetate/hexane to yield 3.1 g of pure 1-[(4-methoxyphenyl)sulfonyl]-heptan-3-ol, m/z=324 (M+NH4).
Reaction SMILES: [OH:1][N:2]1[C:11]2[C:6](=[C:7]3[S:14][C:13](=[O:15])[NH:12][C:8]3=[CH:9][CH:10]=2)[C:5](=[O:16])[C:4]([C:17]([OH:19])=[O:18])=[CH:3]1.[OH-].[K+].O.[CH2:23](Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>CO>[CH2:23]([O:1][N:2]1[C:11]2[C:6](=[C:7]3[S:14][C:13](=[O:15])[N:12]([CH2:5][C:6]4[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=4)[C:8]3=[CH:9][CH:10]=2)[C:5](=[O:16])[C:4]([C:17]([OH:19])=[O:18])=[CH:3]1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: BrCc1ccccc1
Reactant: O=C(O)c1cn(O)c2ccc3[nH]c(=O)sc3c2c1=O
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: O=C(O)c1cn(OCc2ccccc2)c2ccc3c(sc(=O)n3Cc3ccccc3)c2c1=O
Temperature: 25 °C
Reaction time: 44 h

Procedure:
To a mixture of 1.0 g of 2,3,6,9-tetrahydro-6-hydroxy-2,9-dioxothiazolo[5,4-f]quinoline-8-carboxylic acid, 0.96 g of an 85% -- potassium hydroxide aqueous solution, 20 ml of water and 7 ml of methanol was added dropwise 2.77 g of benzyl bromide and the mixture was stirred for 44 hours at room temperature.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[C:8]([CH:10]([CH3:12])[CH3:11])[CH:7]=[C:6]([CH:13]([CH3:15])[CH3:14])[C:5]=1[S:16](Cl)(=[O:18])=[O:17])([CH3:3])[CH3:2].[NH:20]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21]1>>[CH:1]([C:4]1[CH:9]=[C:8]([CH:10]([CH3:12])[CH3:11])[CH:7]=[C:6]([CH:13]([CH3:15])[CH3:14])[C:5]=1[S:16]([N:20]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21]1)(=[O:18])=[O:17])([CH3:3])[CH3:2]
Reactant: c1ccc2[nH]ccc2c1
Reactant: CC(C)c1cc(C(C)C)c(S(=O)(=O)Cl)c(C(C)C)c1
Product: CC(C)c1cc(C(C)C)c(S(=O)(=O)n2ccc3ccccc32)c(C(C)C)c1
Yield: 88 %

Procedure:
The title compound was prepared from 2,4,6-triisopropyl-benzene sulfonyl chloride and 1H-indole, according to Method A, described above. Yield 88%; mp 131-133° C.; 1H NMR (CDCl3) δ 7.41-7.65 (m, 3H), 7.18-7.28 (m, 4H), 6.65-6.68 (dd, J=8 Hz, 1H), 4.15-4.31 (m, 2H), 2.81-2.97 (m, 1H), 1.28 and 1.29 (2s, 6H), 0.98-1.12 (m, 12H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[O:8])[S:5][CH:6]=1.[CH2:9]([Mg]Br)[CH3:10].[Cl-].[NH4+]>C(OCC)C.C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([CH:7]([OH:8])[CH2:9][CH3:10])[S:5][CH:6]=1
Reactant: CC[Mg]Br
Reactant: O=Cc1cc(Br)cs1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCOCC
Product: CCC(O)c1cc(Br)cs1
Reaction time: 2 h

Procedure:
10 g (52 mmol) of 4-bromothiophene-2-carbaldehyde are dissolved in 200 mL of ethyl ether and 20 mL of THF. 26.6 mL (78 mmol) of 3.0M ethylmagnesium bromide are added slowly. After 2 hours at room temperature, the reaction medium is poured into saturated ammonium chloride solution. After extraction, a yellow oil is obtained (m=11.5 g, Y=99%).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:9]3[CH:10]=[CH:11][CH:12]=[C:13]([OH:14])[C:8]=3[O:7][C:6]=2[CH:15]=1.C(N(CC)CC)C.[Si:23](Cl)([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24].C(OCC)(=O)C>C1COCC1.CN(C)C1C=CN=CC=1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:9]3[CH:10]=[CH:11][CH:12]=[C:13]([O:14][Si:23]([C:26]([CH3:29])([CH3:28])[CH3:27])([CH3:25])[CH3:24])[C:8]=3[O:7][C:6]=2[CH:15]=1
Reactant: Oc1cccc2c1oc1cc(Br)ccc12
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: CN(C)c1ccncc1
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(C)(C)[Si](C)(C)Oc1cccc2c1oc1cc(Br)ccc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 95.4 %

Procedure:
To a solution of 3-bromo-6-hydroxydibenzofuran (309 mg, 1.17 mmol) in 8 ml THF at room temperature were added triethylamine (0.23 ml, 1.6 mmol), 4-dimethylaminopyridine (14 mg, 0.12 mmol) and t-butyldimethylsilyl chloride (229 mg, 1.5 mmol). The mixture was stirred at room temperature overnight and then diluted into ethyl acetate and washed successively with NH4Cl (sat.), H2O, and brine. Drying (MgSO4) and evaporation gave 421 mg of brown solid which was purified by flash chromatography through 40 g silica gel (10% EtOAc/hexane) to yield 388 mg (87%) of the title compound.
Reaction SMILES: C[O-].[Na+].CO.[CH2:6]([S:13][C:14]1[N:18]2[C:19](SC)=[N:20][C:21]([F:23])=[CH:22][C:17]2=[N:16][N:15]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C(SC1N=C2N(C(SC)=NC(F)=C2)N=1)C1C=CC=CC=1.C(OCC)(=O)/C=C\[C:49](OCC)=[O:50]>C(O)C.C(O)(=O)C>[CH2:6]([S:13][C:14]1[N:18]=[C:17]2[N:16]([C:19]([O:50][CH3:49])=[N:20][C:21]([F:23])=[CH:22]2)[N:15]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: CCOC(=O)/C=C\C(=O)OCC
Reactant: CSc1nc(F)cc2nnc(SCc3ccccc3)n12
Agent: CSc1nc(F)cc2nc(SCc3ccccc3)nn12
Agent: C[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCO
Solvent: CO
Product: COc1nc(F)cc2nc(SCc3ccccc3)nn12
Yield: 56.7 %

Procedure:
A 25 percent solution of sodium methoxide in methanol (1.9 ml, 0.0085 mol) was added to a solution of 19.9 g (0.065 mol) of 3-benzylthio-7-fluoro-5-methylthio-1,2,4-triazolo[4,3-c]pyrimidine containing a small amount of 2-benzylthio-7-fluoro-5-methylthio-1,2,4-triazolo[1,5-c]pyrimidine and 11.2 g (0.065 mol) of diethyl maleate in 250 ml of ethanol at ambient temperature with stirring and allowed to react for about 1 hour. Acetic acid (4 ml) was then added and the volatiles were removed by evaporation under reduced pressure. The residue was dissolved in methylene chloride and the resulting solution was extracted with water, dried over magnesium sulfate, and concentrated by evaporation under reduced pressure. The residue was triturated with hexane, filtered, and dried to obtain 10.7 g of the title compound as a white powder melting at 121°-122° C. The nmr and uv spectra were consistent with the assigned structure.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([C:7]2[N:12]=[C:11]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[N:10]=[C:9]([C:19]3[CH:24]=[CH:23][C:22]([NH:25][C:26](=[O:37])[NH:27][C:28]4[CH:36]=[CH:35][C:31]([C:32](O)=[O:33])=[CH:30][CH:29]=4)=[CH:21][CH:20]=3)[N:8]=2)[CH2:3][CH2:2]1.CCN(C(C)C)C(C)C.CN(C(O[N:55]1N=N[C:57]2[CH:58]=[CH:59][CH:60]=[CH:61][C:56]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.N1C=CC=CC=1CN>CN1C(=O)CCC1>[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[N:12]=[C:11]([N:13]3[CH2:14][CH2:15][O:16][CH2:17][CH2:18]3)[N:10]=[C:9]([C:19]3[CH:24]=[CH:23][C:22]([NH:25][C:26]([NH:27][C:28]4[CH:29]=[CH:30][C:31]([C:32](=[O:33])[CH2:61][C:60]5[CH:59]=[CH:58][CH:57]=[CH:56][N:55]=5)=[CH:35][CH:36]=4)=[O:37])=[CH:21][CH:20]=3)[N:8]=2)[CH2:3][CH2:2]1
Reactant: O=C(Nc1ccc(C(=O)O)cc1)Nc1ccc(-c2nc(N3CCOCC3)nc(N3CCOCC3)n2)cc1
Reactant: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: NCc1ccccn1
Solvent: CN1CCCC1=O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(Nc1ccc(C(=O)Cc2ccccn2)cc1)Nc1ccc(-c2nc(N3CCOCC3)nc(N3CCOCC3)n2)cc1
Yield: 15.7 %

Procedure:
To the solution of 4-(3-(4-(4,6-dimorpholino-1,3,5-triazin-2yl)phenyl)ureido)benzoic acid (50 mg; 0.099 mmol), Hunig's base (103 μL, 0.594 mmol), HBTU (188 mg, 0.495 mmol) in 2 mL of NMP was reacted according to example 68 with pyridin-2-ylmethanamine (43 mg, 0.396 mmol). Evaporated the solvent and purified by HPLC to give the product (9 mg, 15% yield); MS (ESI) m/z=596.6.
Reaction SMILES: [CH:1]1([NH:4][C:5]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]5[CH:29]=[CH:28][C:27]([CH2:30][N:31]6[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]6)=[CH:26][N:25]=5)[S:23][C:16]=34)=[C:10]([F:37])[CH:9]=2)=[O:6])[CH2:3][CH2:2]1.N1C=CC=CC=1.[C:44](Cl)(=[O:55])[O:45][C:46]1[CH:51]=[CH:50][C:49]([N+:52]([O-:54])=[O:53])=[CH:48][CH:47]=1>CN(C=O)C.[NH4+].[Cl-]>[CH:1]1([NH:4][C:5](=[O:6])[NH:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]4[CH:21]=[C:22]([C:24]5[N:25]=[CH:26][C:27]([CH2:30][N:31]6[CH2:32][CH2:33][N:34]([C:44]([O:45][C:46]7[CH:47]=[CH:48][C:49]([N+:52]([O-:54])=[O:53])=[CH:50][CH:51]=7)=[O:55])[CH2:35][CH2:36]6)=[CH:28][CH:29]=5)[S:23][C:16]=34)=[C:10]([F:37])[CH:9]=2)[CH2:3][CH2:2]1
Reactant: O=C(Nc1ccc(Oc2ccnc3cc(-c4ccc(CN5CCNCC5)cn4)sc23)c(F)c1)NC1CC1
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Agent: [Cl-]
Agent: [NH4+]
Solvent: c1ccncc1
Solvent: CN(C)C=O
Product: O=C(Nc1ccc(Oc2ccnc3cc(-c4ccc(CN5CCN(C(=O)Oc6ccc([N+](=O)[O-])cc6)CC5)cn4)sc23)c(F)c1)NC1CC1
Yield: 64 %

Procedure:
To a solution of compound 49 (0.50 g, 0.96 mmol, scheme 15) and pyridine (0.11 g, 1.4 mmol) in DMF (4 mL) was added 4-nitrophenyl chlorocarbonate (0.23 g, 1.1 mmol). The resultant mixture was stirred at room temperature for 1 h, diluted with saturated NH4Cl aqueous solution and extracted with EtOAc-THF (4:1 mixture). The organic layer was collected, washed with saturated NaHCO3 aqueous solution, water and brine, dried over MgSO4 and concentrated. The residue was triturated with t-BuOMe, to afford title compound 595 (0.42 g, 64% yield) as a beige solid. 1H NMR (300 MHz, DMSO-d6) δ (ppm): 8.72 (s, 1H), 8.60 (s, 1H), 8.53 (d, J=5.4 Hz, 1H), 8.35 (s, 1H), 8.30-8.26 (m, 3H), 7.91 (d, J=8.1 Hz, 1H), 7.74 (dd, J=2.4, 10.8 Hz, 1H), 7.45 (d, J=8.7 Hz, 2H), 7.39 (t, J=9.0 Hz, 1H), 7.21 (d, J=9.0 Hz, 1H), 6.66 (d, J=5.1 Hz, 1H), 6.58 (s, 1H), 3.65 (brs, 4H), 3.49 (brs, 2H), 3.34 (brs, 4H), 2.58-2.54 (m, 1H), 0.70-0.63 (m, 2H), 0.47-0.43 (m, 2H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]1[CH:12]=[N:13][N:14]=[C:7]1[C:6](O)=[N:5]2.P(Cl)(Cl)([Cl:18])=O.C(N(CCC)CCC)CC>>[Cl:18][C:6]1[C:7]2[N:8]([CH:12]=[N:13][N:14]=2)[C:9]2[C:4]([N:5]=1)=[CH:3][C:2]([F:1])=[CH:11][CH:10]=2
Reactant: Oc1nc2cc(F)ccc2n2cnnc12
Reactant: O=P(Cl)(Cl)Cl
Agent: CCCN(CCC)CCC
Product: Fc1ccc2c(c1)nc(Cl)c1nncn12
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
In a flame-dried reaction flask under a dry nitrogen atmosphere, there were placed 8.9 g. (0.044 mole) of 7-fluoro-4-hydroxy-[1,2,4]triazolo[4,3-a]quinoxaline and 160 ml. of phosphorus oxychloride together with 8.9 ml. of tri-n-propylamine. The reaction mixture was then refluxed overnight for approximately 16 hours and finally cooled to room temperature before being poured over ice/water with mechanical stirring. The resulting aqueous mixture was then stirred at room temperature for 30 minutes and filtered, and the solid product so obtained was subsequently washed with cold water and triturated with ethyl acetate to ultimately afford 7.0 g. (71%) of pure 4-chloro-7-fluoro-[1,2,4]triazolo[4,3-a]quinoxaline, m.p. 305°-308° C. Mass spectrum: m/e, 222 (P); m/e, 224 (P+2).
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[Li+].CC([N-]C(C)C)C.[C:21]1([C:27](=[N:30][OH:31])[CH2:28][CH3:29])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[C:32]([O:39][CH2:40][CH3:41])(=[O:38])[C:33]([O:35]CC)=O>C1COCC1>[OH:31][N:30]=[C:27]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH:28]([CH3:29])[C:33](=[O:35])[C:32]([O:39][CH2:40][CH3:41])=[O:38]
Reactant: CCC(=NO)c1ccccc1
Reactant: CCOC(=O)C(=O)OCC
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: CCOC(=O)C(=O)C(C)C(=NO)c1ccccc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 131.7 %

Procedure:
Diisopropylamine (21 mL, 148 mmol) was added to 50 mL of THF and cooled with an external ice bath. Butyllithium (56 mL, 141 mmol, 2.5 M in hexanes) was added and the mixture was stirred at 0° C. for 30 min, and brought to room temperature. The resulting LDA solution was added to a mixture of 1-phenyl-propan-1-one oxime (10 g, 67 mmol) and THF (50 mL) at 0° C. Following the addition, the reaction mixture was stirred at 0° C. for 1 hour and warmed to room temperature. The mixture was then transferred to a syringe and added dropwise to a flask containing a pre-cooled mixture of diethyl oxalate (46 mL, 336 mmol) and THF (150 mL) at 0° C. After the addition was complete, the reaction mixture was stirred at room temperature for 18 hours. The mixture was cooled in an ice bath and quenched with 150 mL of 3M hydrochloric acid. The organic layer was separated and the aqueous layer was extracted with EtOAc. The aqueous layer was then neutralized with solid sodium bicarbonate and extracted further with CH2Cl2. The organic layers were combined, dried over MgSO4 and concentrated. The crude oil was purified by chromatography (0-40% EtOAc/hexanes) to give 22 g of the title compound. MS: (+) m/z 250.48 (M+1).
Reaction SMILES: [Cl:1][C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[CH:14]=[CH:13][CH:12]=3)[N:8](S(C3C=CC=CC=3)(=O)=O)[C:4]=2[N:5]=[CH:6][N:7]=1.[OH-].[Na+]>C1COCC1.CO>[Cl:1][C:2]1[C:3]2[CH:10]=[C:9]([C:11]3[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[CH:14]=[CH:13][CH:12]=3)[NH:8][C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: O=S(=O)(c1ccccc1)n1c(-c2cccc3ccccc23)cc2c(Cl)ncnc21
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: Clc1ncnc2[nH]c(-c3cccc4ccccc34)cc12
Reaction time: 0.25 h
Yield: 69.1 %

Procedure:
To a stirred solution of 4-chloro-6-(1-naphthyl)-7-(phenylsulfonyl)-7H-pyrrolo[2,3-d]pyrimidine (350 mg, 0.73 mmol) in THF (2.50 mL) was added a solution of NaOH (205 mg, 5.13 mmol) in methanol (1.19 mL), and the mixture was stirred for 15 minutes. After quenching by addition of saturated NH4Cl solution (80.0 mL), the mixture was extracted with ethyl acetate (3×100 mL). The organic layers were combined, dried over MgSO4, filtered, and evaporated under vacuum. The residue was dissolved in a small amount of methanol, and the suspension was filtered through a glass pad filter. The white solid was dried under high to afford the title compound (141 mg, 65%).
Reaction SMILES: CC(C[AlH]CC(C)C)C.[C:10]([C:12]1[CH:32]=[CH:31][C:15]2[N:16]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]4[N:30]=[CH:29][CH:28]=[CH:27][N:26]=4)[CH:20]=3)[CH:17]=[N:18][C:14]=2[CH:13]=1)#N.C(Cl)Cl.[NH4+].[Cl-].[OH2:38]>C1(C)C=CC=CC=1>[CH:10]([C:12]1[CH:32]=[CH:31][C:15]2[N:16]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]4[N:30]=[CH:29][CH:28]=[CH:27][N:26]=4)[CH:20]=3)[CH:17]=[N:18][C:14]=2[CH:13]=1)=[O:38]
Reactant: N#Cc1ccc2c(c1)ncn2-c1cccc(-c2ncccn2)c1
Reactant: O
Agent: CC(C)C[AlH]CC(C)C
Agent: [Cl-]
Agent: [NH4+]
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: O=Cc1ccc2c(c1)ncn2-c1cccc(-c2ncccn2)c1
Temperature: -78 °C
Reaction time: 1 h
Yield: 38 %

Procedure:
A solution of DIBAL-H in toluene (2.5 ml, 1.0 M) was added to a mixture of (67) (367 mg, 1.2 mmol) and CH2Cl2 (60 ml) at -78° C. The reaction mixture was stirred for 1 hr at -78° C. and for 1 hr at room temperature. A saturated NH4Cl solution was added to the reaction mixture and stirring was continued for 0.5 hr. The mixture was poured into water and extracted with CH2Cl2. The organic extract was dried over MgSO4, and the solvent was evaporated under reduced pressure to give (68) (142 mg, 38%).
Reaction SMILES: [NH:1]1[CH:5]=[C:4]([C:6]2[CH:22]=[CH:21][C:9]3[C:10]4[N:11]=[C:12]([C:18]([OH:20])=O)[S:13][C:14]=4[CH2:15][CH2:16][O:17][C:8]=3[CH:7]=2)[CH:3]=[N:2]1.[CH3:23][N:24]([CH3:34])[S:25]([N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1)(=[O:27])=[O:26]>>[CH3:23][N:24]([CH3:34])[S:25]([N:28]1[CH2:33][CH2:32][N:31]([C:18]([C:12]2[S:13][C:14]3[CH2:15][CH2:16][O:17][C:8]4[CH:7]=[C:6]([C:4]5[CH:3]=[N:2][NH:1][CH:5]=5)[CH:22]=[CH:21][C:9]=4[C:10]=3[N:11]=2)=[O:20])[CH2:30][CH2:29]1)(=[O:26])=[O:27]
Reactant: CN(C)S(=O)(=O)N1CCNCC1
Reactant: O=C(O)c1nc2c(s1)CCOc1cc(-c3cn[nH]c3)ccc1-2
Product: CN(C)S(=O)(=O)N1CCN(C(=O)c2nc3c(s2)CCOc2cc(-c4cn[nH]c4)ccc2-3)CC1

Procedure:
Following Example 216, to a well stirred solution of 8-(1H-Pyrazol-4-yl)-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid and N,N-dimethylpiperazine-1-sulfonamide were reacted to give 217. MS: (ESI+)=489.1
Reaction SMILES: CC1(C)CO[CH:5]([CH:8]([C@@H:10]2[C@:27]3([CH3:28])[C@H:13]([C@H:14]4[C@H:24]([CH2:25][CH2:26]3)[C@:22]3([CH3:23])[C:17](=[CH:18][C:19](=[O:30])[C@@H:20]5[O:29][C@@H:21]53)C=C4)[CH2:12][CH2:11]2)C)OC1.C(=O)([O-])O.[Na+].ClC1C=CC=[C:40]([C:44]([O:46]O)=O)C=1>C(Cl)Cl>[O:29]1[C:20]2=[C:21]3[C@:22]([CH3:23])([CH2:17][CH2:18][C:19]2=[O:30])[C@@H:24]2[C@H:14]([C@H:13]4[C@:27]([CH3:28])([CH2:26][CH2:25]2)[C@@H:10]([CH2:8][CH3:5])[CH2:11][CH2:12]4)[C@@H:40]2[O:46][C@:44]123
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CC(C1OCC(C)(C)CO1)[C@H]1CC[C@H]2[C@@H]3C=CC4=CC(=O)[C@@H]5O[C@@H]5[C@]4(C)[C@H]3CC[C@]12C
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CC[C@H]1CC[C@H]2[C@@H]3[C@@H]4O[C@]45OC4=C5[C@](C)(CCC4=O)[C@H]3CC[C@]12C
Yield: 79 %

Procedure:
To a solution of 0.43 g (1.0 mmole) of 20-(5,5-dimethyl-1,3-dioxan-2-yl)-1α,2α-epoxypregna-4,6-dien-3-one in 10 ml of methylene chloride was added 3 ml of 0.5M-aqueous sodium hydrogen carbonate solution under stirring and cooling in an ice-water bath, followed by gradual addition of 0.34 g (2.0 mmoles) of m-chloroperbenzoic acid. The mixture was stirred at room temperature for 2 days. The reaction mixture thus obtained was subjected to phase separation and the aqueous layer was extracted twice with 10 ml portions of methylene chloride. The extract was combined with the organic layer obtained above and the mixture was washed successively with aqueous potassium iodide solution and aqueous sodium chloride solution, and dried over magnesium sulfate. The solvent was then distilled off under reduced pressure and the residue was purified by silica gel chromatography (eluent: ethyl acetate-hexane=1:10, v/v) to recover 0.35 g of 20-(5,5-dimethyl-1,3-dioxan-2-yl)-1α,2α;6α,7α-diepoxypregn-4-en-3-one (yield: 79%). The 1H-MNR and IR spectra of this product were in agreement with those of the 20-(5,5-dimethyl-1,3-dioxan-2-yl)-1α,2α;6α,7α-diepoxypregn-4-en-3-one obtained in Example 7.
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[CH:5]=[C:6]([NH:12]N)[CH:7]=[CH:8][C:9]=1[O:10][CH3:11].O.Cl.C(O[CH:19](OCC)[CH2:20][CH2:21][CH2:22][N:23]1[CH2:28][CH2:27][CH2:26][CH2:25][C:24]1=[O:29])C>C(O)C>[CH3:11][O:10][C:9]1[CH:8]=[C:7]2[C:6](=[CH:5][C:4]=1[O:3][CH3:2])[NH:12][CH:19]=[C:20]2[CH2:21][CH2:22][N:23]1[CH2:28][CH2:27][CH2:26][CH2:25][C:24]1=[O:29]
Reactant: CCOC(CCCN1CCCCC1=O)OCC
Reactant: COc1ccc(NN)cc1OC
Agent: Cl
Solvent: CCO
Solvent: O
Product: COc1cc2[nH]cc(CCN3CCCCC3=O)c2cc1OC
Yield: 21.7 %

Procedure:
One dissolves 54 g of 3,4-dimethoxy phenylhydrazine hydrochloride in a mixture of 750 mls of ethanol, 750 mls of water and 350 mls of 5% hydrochloric acid. It is heated under a reflux, and then one adds over a period of 5 minutes a solution of 63 g of 1-(4,4-diethoxybutyl)-2-piperidone in 250 mls of ethanol. After heating under a reflux for 2 hours and then cooling, one eliminates the ethanol by distillation under reduced pressure (20 mm of mercury) and then extracts successively with 500 mls, 300 mls and 200 mls of methylene chloride. The combined organic phases are washed with 500 mls of water and then 500 mls of a saturated solution of sodium bicarbonate, dried over magnesium sulphate and evaporated to dryness under reduced pressure (20 mm of mercury). The residue (58 g) is chromatographed over 1 kg of silica gel contained in a column with a diameter of 6 cm, collecting fractions of 500 mls and eluting with ethyl acetate containing 1.5% of methanol. Fractions 31 to 43 are combined and evaporated to dryness. In this way one obtains 17 g of 1-[2(5,6-dimethoxy-3-indolyl) ethyl]-2-piperidone in the form of a thick yellow oil which slowly crystallises.
Reaction SMILES: [C:1]([NH2:9])(=O)[C:2]1C=[CH:6][CH:5]=[CH:4][CH:3]=1.ClN1[C:16](=[O:17])N(Cl)C(=O)N(Cl)C1=O.O.[OH-].[K+].[Cl:25]CCl>>[Cl:25][CH2:6][C:5]1[C:4]([O:17][CH3:16])=[CH:3][CH:2]=[CH:1][N:9]=1
Reactant: NC(=O)c1ccccc1
Reactant: ClCCl
Reactant: O=c1n(Cl)c(=O)n(Cl)c(=O)n1Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: COc1cccnc1CCl

Procedure:
The title compound of Preparation 45 (190 mg, 1.5 mmol) was added to a stirred solution of benzamide (5 mg, 0.4 mmol) in dichloromethane (2 ml) and the mixture heated to reflux temperature. Trichloroisocyanuric acid (190 mg, 0.82 mmol) was added portionwise, then the reaction mixture stirred under reflux for 3 hours, allowed to cool and treated with water (2 ml) and 50% aqueous potassium hydroxide solution (3 ml). The separated aqueous phase was washed with dichloromethane (3×10 ml) and the combined organic solutions dried (Na2SO4) and evaporated under reduced pressure to yield the title compound (180 mg) as a colourless oil. δ (CDCl3): 3.91 (3H, s), 4.76 (2H, s), 7.25 (2H, m), 8.20 (1H, d). LRMS: m/z 158 (M+1)+.