Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][C:9](=[O:14])[CH2:8]2)#[N:4].Cl[C:16]1[CH:21]=[CH:20][C:19]([CH2:22][N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)=[CH:18][N+:17]=1[O-].P(Cl)(Cl)Cl>CN(C)C=O.C(OCC)(=O)C>[OH:14][C:9]1[NH:10][C:11]2[C:7]([C:8]=1[C:16]1[CH:21]=[CH:20][C:19]([CH2:22][N:23]3[CH2:28][CH2:27][O:26][CH2:25][CH2:24]3)=[CH:18][N:17]=1)=[CH:6][C:5]([C:3]#[N:4])=[CH:13][CH:12]=2
Reactant: N#Cc1ccc2c(c1)CC(=O)N2
Reactant: [O-][n+]1cc(CN2CCOCC2)ccc1Cl
Agent: [H-]
Agent: [Na+]
Solvent: ClP(Cl)Cl
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: N#Cc1ccc2[nH]c(O)c(-c3ccc(CN4CCOCC4)cn3)c2c1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 44.5 %

Procedure:
To a suspension of sodium hydride (105 mg, 2.62 mmol, 60% in oil) in N,N-dimethylformamide (2 mL) was added 5-cyanooxindole (310 mg, 1.96 mmol). The mixture was stirred at room temperature for 10 min. To the obtained yellowish solution was added 2-chloro-5-(morpholin-4-ylmethyl)pyridine 1-oxide (299 mg, 1.31 mmol) and the mixture was heated under nitrogen at 130° C. for 30 min. The dark reaction mixture was allowed to cool and the solvent was removed in vacuo. The residue was partitioned between a 2 M aqueous solution of HCl and ethyl acetate. The aqueous layer was carefully saturated with NaHCO3 (s) and extracted twice with ethyl acetate. The two last organic layers were combined, dried (Na2SO4) and the solvent was removed in vacuo. The residue was dissolved in ethyl acetate (50 mL) and a concentrated solution of phosphorus trichloride (0.5 mL, 5.7 mmol) in ethyl acetate (3 mL) was added. A yellowish precipitate was formed. The mixture was stirred at room temperature overnight and then heated at 60° C. for 30 min and finally at reflux for 10 min. The mixture was allowed to cool and was then diluted with ethyl actetate and washed with a saturated aqueous NaHCO3 solution. The aqueous layer was extracted repeatedly with ethyl acetate. The combined organic layers were dried (Na2SO4) and the solvent was removed in vacuo. The residue was purified on a silica gel column using chloroform/ethyl acetate, (9:1), as the eluent affording 195 mg (45% yield) of the title compound as a yellow solid: mp 228-230° C.; 1H NMR (DMSO-d6, 400 MHz) δ 14.79 (br s, 1 H), 10.87 (s, 1 H), 8.10 (s, 1 H), 7.91 (s, 1 H), 7.84 (d, J=9 Hz, 1 H), 7.79 (dd, J=9, 1 Hz, 1 H), 7.28 (d, J=8 Hz, 1 H), 7.00 (d, J=8 Hz, 1 H), 3.58 (t, J=4 Hz, 4 H), 3.39 (s, 2 H), 2.38 (br s, 4 H); 13C NMR (DMSO-d6, 100 MHz) δ 168.6, 148.4, 142.0, 136.9, 135.9, 125.2, 124.0, 122.3, 121.0, 118.7, 118.3, 108.7, 101.2, 84.4, 66.1, 58.3, 52.8; MS (ESP) m/z 335 (M++1).
Reaction SMILES: [Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)=[C:4](Cl)[N:3]=1.[NH2:17][CH2:18][CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][O:20]1>C(N(CC)CC)C>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)=[C:4]([NH:17][CH2:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][O:20]2)[N:3]=1
Reactant: NCC1CCCCO1
Reactant: Clc1nc(Cl)c2ncn(C3CCCC3)c2n1
Solvent: CCN(CC)CC
Product: Clc1nc(NCC2CCCCO2)c2ncn(C3CCCC3)c2n1

Procedure:
2-Chloro-6-[(2-tetrahydropyranyl)methylamino]-9-cyclopentylpurine is prepared from 2,6-dichloro-9-cyclopentylpurine, 2-aminomethyltetrahydropyran, and triethylamine essentially as described above in Example 1, Scheme A, step b.
Reaction SMILES: CCCCCC.C([Li])CCC.[CH2:12]([O:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1Br)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[CH:27]([C:30]1[CH:37]=[CH:36][C:33]([CH:34]=[O:35])=[CH:32][CH:31]=1)([CH3:29])[CH3:28].O>C1COCC1>[CH2:12]([O:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[CH:34]([C:33]1[CH:36]=[CH:37][C:30]([CH:27]([CH3:29])[CH3:28])=[CH:31][CH:32]=1)[OH:35])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: CC(C)c1ccc(C=O)cc1
Reactant: Brc1ccccc1OCc1ccccc1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Solvent: O
Product: CC(C)c1ccc(C(O)c2ccccc2OCc2ccccc2)cc1
Reaction time: 0.5 h
Yield: 83.4 %

Procedure:
In a nitrogen stream, an n-butyllithium hexane solution (2.44 M, 5.14 mL) was added dropwise to a solution of 1-benzyloxy-2-bromobenzene (3.0 g, 11.4 mmol) in THF (114 mL) at −78° C. and the reaction mixture was stirred at the same temperature for 30 minutes. To this solution, a solution of 4-isopropylbenzaldehyde (1.41 g, 9.49 mmol) in THF (38 mL) was added dropwise at −78° C. The reaction mixture was stirred at the same temperature for one hour and furthermore at 0° C. for one hour. Water was added thereto and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated sodium chloride aqueous solution and dried (anhydrous magnesium sulfate), and then the solvent was distilled under reduced pressure. The obtained residue was purified by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:5)] to obtain the title compound (2.63 g, 84%).
Reaction SMILES: C(N(CC)CC)C.[CH2:8]([O:10][C:11]1[CH:19]=[CH:18][C:17]([S:20]([N:23]2[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]2)(=[O:22])=[O:21])=[CH:16][C:12]=1[C:13]([NH2:15])=O)[CH3:9].FC(F)(F)C(OC(=O)C(F)(F)F)=O>ClCCl>[CH2:8]([O:10][C:11]1[CH:19]=[CH:18][C:17]([S:20]([N:23]2[CH2:24][CH2:25][N:26]([CH3:29])[CH2:27][CH2:28]2)(=[O:22])=[O:21])=[CH:16][C:12]=1[C:13]#[N:15])[CH3:9]
Reactant: CCOc1ccc(S(=O)(=O)N2CCN(C)CC2)cc1C(N)=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Product: CCOc1ccc(S(=O)(=O)N2CCN(C)CC2)cc1C#N
Temperature: 0 °C
Reaction time: 18 h

Procedure:
Triethylamine (49.1 g, 0.485 Mol) was added to a slurry of 2-ethoxy-5-(4-methyl-1-piperazinylsulfonyl)benzamide (40.9 g, 0.125 Mol) in dichloromethane (200 mL) and this mixture was cooled to 0° C. Trifluoroacetic anhydride (58.9 g, 0.28 Mol) was added dropwise over 45 min and was washed in with DCM (25 mL) before the reaction was stirred at ambient temperature for 18 h. Water (125 mL) was added to the reaction with cooling. The layers were separated and the organic phase was washed with water before evaporation. The residue was stirred with ethyl acetate (150 mL) giving a crystalline solid which was filtered off and dried under vacuum; 27.4 g, 71%. m.p.=130-131° C. M/Z=310 (M+H); 1H NMR (300 MHz, CDCl3): 1.55 (t, 3H), 2.30 (s, 3H), 2,50 (m, 4H), 3.06 (m, 4H), 4.26 (quart. 2H), 7.08 (d, 1H), 7.90 (dd, 1H), 7.97 (d, 1H)
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH2:7](I)[CH3:8].[CH3:10][C:11]1[C:16]([CH3:17])=[CH:15][CH:14]=[C:13]([CH3:18])[C:12]=1[OH:19]>C(#N)C.C(OCC)(=O)C>[CH2:7]([O:19][C:12]1[C:11]([CH3:10])=[C:16]([CH3:17])[CH:15]=[CH:14][C:13]=1[CH3:18])[CH3:8]
Reactant: CCI
Reactant: Cc1ccc(C)c(O)c1C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: CCOC(C)=O
Product: CCOc1c(C)ccc(C)c1C

Procedure:
734 mmol (101.5 g) of potassium carbonate and 917 mmol (143.1 g) of ethyl iodide are added in succession to a solution of 367 mmol (50 g) of 2,3,6-trimethylphenol in 1500 ml of acetonitrile. The whole is heated at reflux for 48 hours. The reaction mixture is subsequently cooled and then filtered and the filtrate is concentrated. The residue obtained is dissolved in ethyl acetate and washed with water and then with 10% aqueous sodium chloride solution. After drying the organic phase and then concentrating, an oily residue is obtained which is purified by chromatography on silica gel, using a petroleum ether: ethyl acetate mixture 95:5 as eluant, to yield the expected product.
Reaction SMILES: [C:1]([C:5]1[S:9][C:8]([N:10]=[C:11]=[O:12])=[N:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:13][NH:14][CH2:15][CH:16]=[O:17]>C1C=CC=CC=1>[CH3:13][N:14]([CH2:15][CH:16]=[O:17])[C:11]([NH:10][C:8]1[S:9][C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[N:6][N:7]=1)=[O:12]
Reactant: CC(C)(C)c1nnc(N=C=O)s1
Reactant: CNCC=O
Solvent: c1ccccc1
Product: CN(CC=O)C(=O)Nc1nnc(C(C)(C)C)s1
Reaction time: 0.08 h

Procedure:
A mixture of 5-t-butyl-1,3,4-thiadiazol-2-yl isocyanate dimer (6 grams), the dimethyl acetal of 2-methylaminoacetaldehyde (3.9 grams) and benzene (50 ml) were charged into a glass reaction flask equipped with a mechanical stirrer and reflux condenser. The reaction mixture was heated at reflux, with stirring for a period of about 5 minutes. After this time the reaction mixture was stripped of benzene to yield an oil which solidified upon standing. The resulting solid was then recrystallized from pentane to yield the desired product the dimethyl acetal of 2-[1-methyl-3-(5-t-butyl-1,3,4-thiadiazol-2-yl)ureido] acetaldehyde having a melting point of 80° to 82° C.
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:10]([NH:17][C:18]2[S:19][CH:20]=[C:21]([CH3:23])[N:22]=2)=[N:11][CH:12]=[C:13]([CH:16]=1)[CH:14]=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C(=O)(O)[O-].[Na+].[ClH:49]>C1COCC1>[ClH:49].[ClH:49].[CH2:1]([O:8][C:9]1[C:10]([NH:17][C:18]2[S:19][CH:20]=[C:21]([CH3:23])[N:22]=2)=[N:11][CH:12]=[C:13]([CH2:14][N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[CH:16]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C1COCCN1
Reactant: Cc1csc(Nc2ncc(C=O)cc2OCc2ccccc2)n1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: O=C([O-])O
Solvent: C1CCOC1
Product: Cc1csc(Nc2ncc(CN3CCOCC3)cc2OCc2ccccc2)n1
Reaction time: 0.17 h
Yield: 70.49 %

Procedure:
A 20 mL vial was charged with 5-(benzyloxy)-6-(4-methylthiazol-2-ylamino)nicotinaldehyde (100 mg, 0.31 mmol) and THF (3 mL). morpholine (0.032 ml, 0.37 mmol) was added and the reaction was stirred for 10 minutes. NaBH(OAc)3 (326 mg, 1.54 mmol) was added and the reaction was stirred for 30 minutes. The reaction was poured into saturated sodium bicarbonate and extracted with EtOAc. The organic layer was washed with water and brine and then dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified on silica gel (0 to 10% methanol in EtOAc containing ammonia) to afford the title compound (101.7 mg, 70.49% yield) as a white solid after HCl salt formation. 1H NMR (DMSO-d6) δ 11.77 (bs, 1H), 11.05 (bs, 1H), 8.08 (m, 2H), 7.64 (d, 2H), 7.45-7.32 (m, 3H), 6.83 (s, 1H), 5.35 (s, 2H), 4.32 (d, 2H), 3.87 (m, 4H), 3.20 (d, 2H), 3.03 (m, 2H), 2.31 (s, 3H). Mass spectrum (apci) m/z=397.1 (M+H-2HCl).
Reaction SMILES: [CH3:1][C:2]1[S:6][C:5]([CH:7]2[CH2:12][C:11](=O)[CH2:10][C:9](=[O:14])[CH2:8]2)=[CH:4][CH:3]=1.C([O-])(=O)C.[NH4+:19]>C(O)C>[NH2:19][C:11]1[CH2:12][CH:7]([C:5]2[S:6][C:2]([CH3:1])=[CH:3][CH:4]=2)[CH2:8][C:9](=[O:14])[CH:10]=1
Reactant: Cc1ccc(C2CC(=O)CC(=O)C2)s1
Reactant: [NH4+]
Agent: CC(=O)[O-]
Solvent: CCO
Product: Cc1ccc(C2CC(=O)C=C(N)C2)s1
Yield: 81.4 %

Procedure:
A mixture of 5-(5-methyl-2-thienyl)cyclohexane-1,3-dione (4.16 g) and ammonium acetate (4.6 g) in ethanol (50 ml) was refluxed for 15 hours, and the reaction solution was concentrated under reduced pressure. To the residue was added water (60 ml), and the resulting crystals were filtered. The crystals were washed with water and toluene, and dried to give 1-amino-5-(5-methyl-2-thienyl)cyclohexen-3-one (3.37 g) as pale yellow crystals.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([C:12]2[CH:17]([CH2:18][C:19]3[C:24]([CH3:25])=[CH:23][C:22]([CH3:26])=[CH:21][C:20]=3[CH3:27])[NH:16][C:15]([CH3:28])=[N:14][CH:13]=2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.C[N+]1([O-])CCOCC1>CCC[N+](CCC)(CCC)CCC.[O-][Ru](=O)(=O)=O.C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([C:12]2[C:17]([CH2:18][C:19]3[C:20]([CH3:27])=[CH:21][C:22]([CH3:26])=[CH:23][C:24]=3[CH3:25])=[N:16][C:15]([CH3:28])=[N:14][CH:13]=2)(=[O:11])=[O:10])=[CH:5][CH:4]=1
Reactant: COc1ccc(S(=O)(=O)C2=CN=C(C)NC2Cc2c(C)cc(C)cc2C)cc1
Agent: O=[Ru](=O)(=O)[O-]
Agent: CCC[N+](CCC)(CCC)CCC
Agent: C[N+]1([O-])CCOCC1
Solvent: ClCCl
Product: COc1ccc(S(=O)(=O)c2cnc(C)nc2Cc2c(C)cc(C)cc2C)cc1
Yield: 82.3 %

Procedure:
A mixture 5-(4-methoxy-benzenesulfonyl)-2-methyl-6-(2,4,6-trimethylbenzyl)-1,6-dihydro-pyrimidine (167 mg, 0.42 mmol), NMO (74 mg, 0.63 mmol), TPAP (29 mg, 0.084 mmol), 4 Å molecular sieves (200 mg) and CH2Cl2 (5 mL) was stirred under N2 at room temperature for 2 h. The mixture was filtered through a pad of silica gel and the filtrate was concentrated in vacuo. The residue was purified by chromatography on silica gel (67:33 hexanes/EtOAc) to provide the target compound (137 mg, 82%) as a light yellow solid: mp 150–152° C.; 1H NMR (500 MHz, CDCl3) δ 9.22 (s, 1H), 7.93 (d, J=8.9 Hz, 2H), 7.06 (d, J=8.9 Hz, 2H), 6.83 (s, 2H), 4.25 (s, 2H), 3.91 (s, 3H), 2.59 (s, 3H), 2.29 (s, 3H), 1.91 (s, 6H); ESI MS m/z 397 [(M+H)+, calcd for C22H25N2O3S, 397.2].
Reaction SMILES: [N:1]1([C:6]2[CH:12]=[CH:11][C:9]([NH2:10])=[CH:8][CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.C(N(CC)CC)C.[Cl-].ClC1N(C)CC[NH+]1C.[CH3:29][O:30][C:31]1[C:32](=[O:55])[C:33]([CH3:54])=[C:34]([CH2:40][C:41]2[CH:42]=[CH:43][C:44]([O:50][C:51](=[O:53])[CH3:52])=[C:45]([CH:49]=2)[C:46](O)=[O:47])[C:35](=[O:39])[C:36]=1[O:37][CH3:38]>C(Cl)Cl>[CH3:29][O:30][C:31]1[C:32](=[O:55])[C:33]([CH3:54])=[C:34]([CH2:40][C:41]2[CH:42]=[CH:43][C:44]([O:50][C:51](=[O:53])[CH3:52])=[C:45]([CH:49]=2)[C:46]([NH:10][C:9]2[CH:11]=[CH:12][C:6]([N:1]3[CH:5]=[CH:4][N:3]=[CH:2]3)=[CH:7][CH:8]=2)=[O:47])[C:35](=[O:39])[C:36]=1[O:37][CH3:38]
Reactant: Nc1ccc(-n2ccnc2)cc1
Reactant: COC1=C(OC)C(=O)C(Cc2ccc(OC(C)=O)c(C(=O)O)c2)=C(C)C1=O
Agent: CN1CC[NH+](C)C1Cl
Agent: [Cl-]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC1=C(OC)C(=O)C(Cc2ccc(OC(C)=O)c(C(=O)Nc3ccc(-n4ccnc4)cc3)c2)=C(C)C1=O
Temperature: 25 °C
Reaction time: 3 h
Yield: 40.7 %

Procedure:
4-(1H-Imidazol-1-yl)aniline (0.159 g, 1.003 mmol), triethylamine (0.101 g, 1.003 mmol) and 2-chloro-1,3-dimethylimidazolinium chloride (0.170 g, 1.003 mmol) were added to a methylene chloride solution (100 ml) of 5-(5,6-dimethoxy-3-methyl-1,4-benzoquinon-2-yl)methyl-2-acetoxybenzoic acid (0.250 g, 0.668 mmol) and the resulting solution was stirred at room temperature for 3 hours. The reaction solution was poured into ice water and then extracted with methylene chloride. The extract was washed with water and then dried, and the solvent was removed by distillation. The obtained residue was purified by preparative thin-layer chromatography (chloroform:methanol=10:1) and then recrystallized from a mixed solvent of ethyl acetate and hexane (2:1) to obtain the titled compound (0.140 g, 0.272 mmol, 41%).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.[S:10]1[CH2:14][C:13](=[O:15])[NH:12][C:11]1=[O:16].N1CCCCC1>C(O)C>[CH:4]1[C:5](/[CH:6]=[C:14]2\[C:13]([NH:12][C:11]([S:10]\2)=[O:16])=[O:15])=[CH:8][CH:9]=[C:2]([OH:1])[CH:3]=1
Reactant: O=Cc1ccc(O)cc1
Reactant: O=C1CSC(=O)N1
Solvent: CCO
Solvent: C1CCNCC1
Product: O=C1NC(=O)/C(=C\c2ccc(O)cc2)S1

Procedure:
4-(Thiazolidin-2,4-dione-5-ylidinemethyl)-phenol (38) was synthesized by the condensation of 4-hydroxy benzaldehyde (36) with commercially available 2,4-thiazolidinedione (37) using piperidine as base in refluxing ethanol, according to a known procedure (Momose, Y.; Meguro, K.; Ikeda, H.; Hatanaka, C.; Oi, S.; Sohda, T. Chem. Pharm. Bull. 1991, 39, 1440.) (Scheme 2)
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:7])[C:5]#[CH:6])[CH3:2].[CH3:8][CH:9]([CH2:13][CH2:14][CH:15]=[C:16]([CH3:18])[CH3:17])[CH2:10][CH2:11][OH:12].CN1CCOCC1>C(OCC)C>[CH2:1]([O:3][C:4](=[O:7])/[CH:5]=[CH:6]/[O:12][CH2:11][CH2:10][CH:9]([CH3:8])[CH2:13][CH2:14][CH:15]=[C:16]([CH3:18])[CH3:17])[CH3:2]
Reactant: C#CC(=O)OCC
Reactant: CC(C)=CCCC(C)CCO
Solvent: CCOCC
Solvent: CN1CCOCC1
Product: CCOC(=O)/C=C/OCCC(C)CCC=C(C)C
Temperature: 25 °C
Reaction time: 24 h
Yield: 9.3 %

Procedure:
The reaction was performed in standard glassware under an atmosphere of N2. To 100 ml of diethylether were added 8.0 g (0.82 mol) propiolic acid ethyl ester, 12.8 g (0.82 mol) 3,7-dimethyl-oct-6-en1-ol and 8.3 g (0.82 mol) N-methylmorpholine. This solution was kept without stirring at room temperature for 24 hours. The mixture was evaporated under vacuum and the residue purified by bulb to bulb distillation (bp: 70-75° C.; 0.006 mbar) to yield 19.4 g (76%) of an oil.
Reaction SMILES: Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]1([CH2:22][O:21][C:20]3[CH:23]=[C:24]4[C:28](=[CH:29][C:19]1=3)[CH2:27][CH2:26][O:25]4)[C:5](=[O:18])[N:6]2[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=1.[N:30]1[CH:35]=[CH:34][CH:33]=[C:32](B(O)O)[CH:31]=1.CN(C)C1N=CC(B(O)O)=CC=1>>[N:30]1[CH:35]=[CH:34][CH:33]=[C:32]([C:2]2[CH:10]=[CH:9][CH:8]=[C:7]3[C:3]=2[C:4]2([CH2:22][O:21][C:20]4[CH:23]=[C:24]5[C:28](=[CH:29][C:19]2=4)[CH2:27][CH2:26][O:25]5)[C:5](=[O:18])[N:6]3[CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)[CH:31]=1
Reactant: OB(O)c1cccnc1
Reactant: O=C1N(Cc2ccccn2)c2cccc(Br)c2C12COc1cc3c(cc12)CCO3
Agent: CN(C)c1ccc(B(O)O)cn1
Product: O=C1N(Cc2ccccn2)c2cccc(-c3cccnc3)c2C12COc1cc3c(cc12)CCO3

Procedure:
Following the procedure as described in EXAMPLE 4, and making non-critical variations using 4′-bromo-1′-(pyridin-2-ylmethyl)-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1′H)-one to replace 4′-bromo-1-pentylspiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one, and pyridin-3-ylboronic acid to replace [6-(dimethylamino)pyridin-3-yl]boronic acid, the title compound was obtained (9%) as a colorless solid: mp >200° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.52 (d, 1H), 8.42 (d, 1H), 7.96 (s, 1H), 7.79 (t, 1H), 7.40 (d, 1H), 7.29 (t, 2H), 7.18-7.08 (m, 2H), 7.00 (d, 1H), 6.81 (d, 1H), 6.72 (s, 1H), 5.98 (s, 1H), 5.08 (ABq, 2H), 4.56-4.40 (m, 4H), 3.10-2.90 (m, 2H); MS (ES+) m/z 448.5 (M+1).
Reaction SMILES: [Cl:1][C:2]1[C:3]([SH:16])=[C:4]([S:10]([N:13]([CH3:15])[CH3:14])(=[O:12])=[O:11])[CH:5]=[C:6]([Cl:9])[C:7]=1[Cl:8].C[O-].[Na+].Cl[CH2:21][S:22][C:23]#[N:24]>CO.C(Cl)(Cl)Cl>[Cl:1][C:2]1[C:3]([S:16][CH2:21][S:22][C:23]#[N:24])=[C:4]([S:10]([N:13]([CH3:14])[CH3:15])(=[O:11])=[O:12])[CH:5]=[C:6]([Cl:9])[C:7]=1[Cl:8]
Reactant: CN(C)S(=O)(=O)c1cc(Cl)c(Cl)c(Cl)c1S
Reactant: N#CSCCl
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Solvent: ClC(Cl)Cl
Product: CN(C)S(=O)(=O)c1cc(Cl)c(Cl)c(Cl)c1SCSC#N
Temperature: 62 °C
Reaction time: 0.25 h

Procedure:
To a stirring mixture a 1.5 grams (0.0047 mole) of 3,4,5-trichloro-N,N-dimethyl-2-(mercapto)benzenesulfonamide in 80 milliliters of methanol at 25° C, was added 0.39 grams of sodium methoxide. The mixture was stirred for 15 minutes and thereafter 1.0 gram (0.009 mole) of chloromethylthiocyanate was added thereto and the mixture stirred at room temperature for 3 hours. At the end of this time period, the reaction mixture was filtered to remove the solids which had precipitated. The filtrate further heated at 62° C for 2 hours and after cooling, the solvent was reduced in volume by evaporation under reduced pressure. The solids were thereafter removed by filtration. Additional filtrations gave additional solids. The recovered solids were combined and dissolved in chloroform and filtered. The solvent was removed by evaporation under reduced pressure and the solid product which remained was air dried. The 3,4,5-trichloro-N,N-dimethyl-2-((thiocyanomethyl)thio)benzenesulfonamide product was recovered in a yield of 0.7 grams (40 percent of theoretical) and melted at 155°-156° C.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13]3[CH:18]=[CH:17][N:16]=[C:15]4[CH2:19][CH2:20][CH2:21][C:14]=34)=[CH:11][N:10]([CH3:22])[N:9]=2)=[CH:4][CH:3]=1.CC[O:25]C(C)=O.CO>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:12]([C:13]3[CH:18]=[CH:17][N+:16]([O-:25])=[C:15]4[CH2:19][CH2:20][CH2:21][C:14]=34)=[CH:11][N:10]([CH3:22])[N:9]=2)=[CH:6][CH:7]=1
Reactant: CCOC(C)=O
Reactant: Cn1cc(-c2ccnc3c2CCC3)c(-c2ccc(F)cc2)n1
Solvent: CO
Product: Cn1cc(-c2cc[n+]([O-])c3c2CCC3)c(-c2ccc(F)cc2)n1

Procedure:
4-[3-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]-6,7-dihydro-5H-cyclopenta[b]pyridine was converted to the N-oxide following the general procedure described in Example 1, step 9. Silica gel chromatography using a 9:1 to 4:1 mixture of EtOAc/MeOH afforded 54% of Ex 24-Step 1 product as a yellow solid: LCMS m/z 310.5 (M+1); 1H NMR (400 MHz, CDCl3) δ 7.97 (d, J=6.6, 1H), 7.45 (s, 1H), 7.35 (dd, J=8.9, 5.4, 2H), 7.00 (dd, J=8.7, 8.7, 2H), 6.89 (d, J=6.6, 1H), 3.97 (s, 3H), 3.17 (t, J=7.6, 2H), 2.67 (t, J=7.6, 2H), 2.02-2.09 (m, 2H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:23]=[CH:22][C:6]([C:7]([N:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH:12]([C:19](O)=[O:20])[CH2:11][CH2:10]2)=[O:8])=[CH:5][CH:4]=1.C(Cl)(=O)C(Cl)=O.C(N(C(C)C)CC)(C)C.[Cl:39][C:40]1[CH:48]=[CH:47][C:43]([NH:44][CH2:45][CH3:46])=[CH:42][CH:41]=1>C(Cl)Cl.CN(C)C=O.C(OCC)(=O)C>[Cl:39][C:40]1[CH:48]=[CH:47][C:43]([N:44]([CH2:45][CH3:46])[C:19]([CH:12]2[C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[N:9]([C:7](=[O:8])[C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:23][CH:22]=3)[CH2:10][CH2:11]2)=[O:20])=[CH:42][CH:41]=1
Reactant: CCNc1ccc(Cl)cc1
Reactant: COc1ccc(C(=O)N2CCC(C(=O)O)c3ccccc32)cc1
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCN(C(=O)C1CCN(C(=O)c2ccc(OC)cc2)c2ccccc21)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 29.2 %

Procedure:
1-(4-Methoxy-benzoyl)-1,2,3,4-tetrahydro-quinoline-4-carboxylic acid (approx. 1.47 mmol) was suspended in methylene chloride (10 mL) to which one drop of dimethylformamide was added. Oxalyl chloride (375 mg, 275 uL, 2.95 mmol) was added. Vigorous bubbling ensued, followed by dissolution of the starting material. After stirring for 4 hours at room temperature, the yellow solution was concentrated and azeotroped with toluene to remove excess oxalyl chloride. The resulting acid chloride solution was dissolved in methylene chloride (10 mL). Diisopropylethylamine (569 mg, 768 uL, 4.41 mmol) was added, followed by 4-chloro-N-ethylaniline (457 mg, 2.93 mmol). The mixture was stirred at room temperature overnight. The reaction was poured into ethyl acetate and washed with water and brine. The combined organics were dried over sodium sulfate, filtered and concentrated. The crude residue was purified by silica gel chromatography (ethyl acetate/hexanes gradient) to afford (±)-1-(4-methoxy-benzoyl)-1,2,3,4-tetrahydro-quinoline-4-carboxylic acid (4-chloro-phenyl)-ethyl-amide (193 mg) as a foam. 1H-NMR (CDCl3) δ: 1.17 (t, 3H), 2.06-2.26 (m, 2H), 3.57-3.70 (m, 2H), 3.73-3.87 (m, 5H), 4.02 (dd, 1H), 6.52 (d, 1H), 6.66-6.74 (m, 2H), 6.84 (ddd, 1H), 6.93-7.06 (m, 2H), 7.17-7.24 (m, 2H), 7.37-7.43 (m, 2H). MS m/z: 449 (M+1).
Reaction SMILES: [CH:1]1([C:7]2[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Br[CH2:15][CH2:16][O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O.C(OCC)(=O)C>[CH2:18]([O:17][CH2:16][CH2:15][O:13][C:10]1[CH:9]=[CH:8][C:7]([CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]2)=[CH:12][CH:11]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: Oc1ccc(C2CCCCC2)cc1
Reactant: BrCCOCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: O
Product: c1ccc(COCCOc2ccc(C3CCCCC3)cc2)cc1
Temperature: 60 °C
Reaction time: 23 h
Yield: 90.1 %

Procedure:
A suspension of 2.5 g of 4-cyclohexylphenol, 3.0 g of benzyl 2-bromoethyl ether and 2.4 g of potassium carbonate in N,N-dimethylformamide (50 ml) was stirred at 60° C. for 23 hours. The reaction solution was diluted with water and ethyl acetate. The organic layer was washed with saturated aqueous potassium carbonate and saturated ammonium chloride (×2), dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography, to give 3.9 g of the title compound as a colorless oil.