Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[C:7]([CH:8]=[O:9])=[C:6]([N:10]2[CH:22]=[CH:21][C:20]3[N:19]4[C:14]([CH2:15][CH2:16][CH2:17][CH2:18]4)=[CH:13][C:12]=3[C:11]2=[O:23])[N:5]=[CH:4][CH:3]=1.[CH3:24][N:25]1[C:29]([CH3:30])=[CH:28][C:27]([NH:31][C:32]2[C:33](=[O:48])[N:34]([CH3:47])[CH:35]=[C:36](B3OC(C)(C)C(C)(C)O3)[CH:37]=2)=[N:26]1.C([O-])(=O)C.[Na+].[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O.C(#N)C>[CH3:24][N:25]1[C:29]([CH3:30])=[CH:28][C:27]([NH:31][C:32]2[C:33](=[O:48])[N:34]([CH3:47])[CH:35]=[C:36]([C:2]3[C:7]([CH:8]=[O:9])=[C:6]([N:10]4[CH:22]=[CH:21][C:20]5[N:19]6[C:14]([CH2:15][CH2:16][CH2:17][CH2:18]6)=[CH:13][C:12]=5[C:11]4=[O:23])[N:5]=[CH:4][CH:3]=3)[CH:37]=2)=[N:26]1
Reactant: O=Cc1c(Cl)ccnc1-n1ccc2c(cc3n2CCCC3)c1=O
Reactant: Cc1cc(Nc2cc(B3OC(C)(C)C(C)(C)O3)cn(C)c2=O)nn1C
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: CC(=O)[O-]
Solvent: O
Solvent: CC#N
Product: Cc1cc(Nc2cc(-c3ccnc(-n4ccc5c(cc6n5CCCC6)c4=O)c3C=O)cn(C)c2=O)nn1C
Temperature: 90 °C
Yield: 19.1 %

Procedure:
A 50-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 4-chloro-2-(1-oxo-6,7,8,9-tetrahydropyrido[3,4-b]indolizin-2(1H)-yl)nicotinaldehyde 245a (130 mg, 0.39 mmol, 1.0 eq.), 3-(1,5-dimethyl-1H-pyrazol-3-ylamino)-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2(1H)-one 218a (600 mg, 1.75 mmol, 4.0 eq.), Pd(dppf)Cl2 (32 mg, 0.040 mmol, 0.1 eq.), sodium acetate (64 mg, 0.78 mmol, 2.0 eq.), K3PO4 (165 mg, 0.78 mmol, 2.0 eq.), acetonitrile (15 mL), and water (1 mL). After three cycles of vacuum/argon flush, the mixture was heated at 90° C. for 2 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica-gel column chromatography eluting with 50:1 dichloromethane/ethanol to afford 246a (38 mg, 19%) as a yellow solid. MS-ESI: [M+H]+ 510.3.
Reaction SMILES: C(OC(=O)[C:5]([NH:7][C:8]1[CH:13]=[CH:12][N:11]=[C:10]([C:14]2[CH2:23][CH2:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH:15]=2)[CH:9]=1)=O)C.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[CH:15]1[C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:22][CH2:23][C:14]=1[C:10]1[CH:9]=[C:8]([NH:7][CH3:5])[CH:13]=[CH:12][N:11]=1
Reactant: CCOC(=O)C(=O)Nc1ccnc(C2=Cc3ccccc3CC2)c1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: CNc1ccnc(C2=Cc3ccccc3CC2)c1
Yield: 42.3 %

Procedure:
A solution of N-[2-(3,4-dihydro-naphthalen-2-yl)-pyridin-4-yl]-oxalamic acid ethyl ester (0.36 g, 1.2 mmol) in THF (20 ml) was slowly added to an ice bath cooled mixture of lithium aluminum hydride (0.10 g, 2.6 mmol) in THF (20 ml). The resulting mixture was refluxed for 30 min, quenched with aqueous saturated Seignette-salt solution and extracted with AcOEt. The organic phase was dried over Na2SO4, concentrated and chromatographed (SiO2 with CH2Cl2/CH3OH/NH4OH=140/10/1) to give [2-(3,4-dihydro-naphthalen-2-yl)-pyridin-4-yl]-methyl-amine as a yellow oil (0.12 g, 42%) which was crystallized as the white fumarate salt. Mp. 106–107° C. (MeOH/Et2O), MS: m/e=236 (M+).
Reaction SMILES: [N:1]1([C:8]2[C:9]([C:22]3[O:23][C:24]4[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:25]=4[CH:26]=3)=[N:10][C:11]3[C:16]([N:17]=2)=[CH:15][C:14]([C:18]([O:20]C)=[O:19])=[CH:13][CH:12]=3)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[Na+].O>CO.C(Cl)(Cl)Cl>[N:1]1([C:8]2[C:9]([C:22]3[O:23][C:24]4[CH:30]=[C:29]([F:31])[CH:28]=[CH:27][C:25]=4[CH:26]=3)=[N:10][C:11]3[C:16]([N:17]=2)=[CH:15][C:14]([C:18]([OH:20])=[O:19])=[CH:13][CH:12]=3)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]1
Reactant: COC(=O)c1ccc2nc(-c3cc4ccc(F)cc4o3)c(N3CCCCCC3)nc2c1
Agent: [Na+]
Agent: [OH-]
Solvent: ClC(Cl)Cl
Solvent: CO
Solvent: O
Product: O=C(O)c1ccc2nc(-c3cc4ccc(F)cc4o3)c(N3CCCCCC3)nc2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 56.6 %

Procedure:
To a solution of methyl 3-(azepan-1-yl)-2-(6-fluoro-1-benzofuran-2-yl)quinoxaline-6-carboxylate (73 mg, 0.17 mmol) in methanol (25 mL) and chloroform (5 mL) was added sodium hydroxide (13.6 mg, 0.34 mmol) and water (2 mL) with stirring overnight at room temperature. The reaction mixture was concentrated under vacuum, dissolved in water (15 mL), adjusted pH to 5 with HCl (3 N) to give the precipitate, which was collected by filtration to afford 3-(azepan-1-yl)-2-(6-fluoro-1-benzofuran-2-yl)quinoxaline-6-carboxylic acid (39 mg, 55%).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[N:9]1[CH:13]=[N:12][CH:11]=[N:10]1.[CH2:14]=[O:15]>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[N:9]1[C:13]([CH2:14][OH:15])=[N:12][CH:11]=[N:10]1
Reactant: C=O
Reactant: Fc1ccc(Br)c(-n2cncn2)c1
Product: OCc1ncnn1-c1cc(F)ccc1Br
Temperature: 150 °C

Procedure:
A suspension of 1-(2-bromo-5-fluorophenyl)-1H-1,2,4-triazole (3.63 g, 15 mmol) in 37% formaline (15 mL) in a sealed vessel was stirred in an oil bath heated at 150° C. for 9.5 h. After cooling, the mixture was extracted with CH2Cl2 (15 mL×2) and the combined extracts were washed with brine, dried (Na2SO4), filtered and concentrated. The residual crude oil was purified by column chromatography (SiO2, 0-7% MeOH/CH2C12) followed by trituration with Et2O to obtain 430 mg of the title compound as white crystalline solid: TLC Rf 0.5 (10% MeOH/CH2Cl2); HPLC rt=1.31 min; LC/MS m/z 272/274 (M+H); 1H NMR (CDCl3, 500 MHz) δ ppm 3.67 (1H, br.s, OH), 4.65 (2H, s, 9-OCH2), 7.13-7.22 (1H, m, 5-CH), 7.29 (1H, dd, J=8, 3 Hz, 3-CH), 7.71 (1H, dd, J=9.0, 5.3 Hz, 6-CH), 8.03 (1H, s, 8-CH); 13C NMR (CDCl3, 125.8 Hz) δ ppm 55.3 (9-OCH2), 116.2 (d, J=3.9 Hz, 1-C), 117.4 (d, J=25 Hz, 3-CH), 119.4 (d, J=22 Hz, 5-CH), 134.7 (d, J=8.3 Hz, 6-CH), 137.0 (d, J=10 Hz, 2-C), 151.3 (8-CH), 156.3 (7-C), 161.8 (d, J=252 Hz, 4-CF); HRMS (ESI) calcd for C9H8BrN3O (M+H) 271.9835; found 271.9828 (δ-2.5 ppm).
Reaction SMILES: C([Si](C)(C)[O:6][C:7]1[C:12]([CH3:13])=[CH:11][C:10]([C:14]2([C:24]3[CH:29]=[C:28]([CH3:30])[C:27]([O:31][Si](C(C)(C)C)(C)C)=[C:26]([CH3:39])[CH:25]=3)[C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[NH:16][C:15]2=[O:23])=[CH:9][C:8]=1[CH3:40])(C)(C)C.[CH2:43]([O:45][C:46]1[CH:47]=[C:48](B(O)O)[CH:49]=[CH:50][CH:51]=1)[CH3:44].C(N(CC)CC)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C1COCC1.C([O-])(=O)C.[Cu+2].C([O-])(=O)C.ClCCl>[CH2:43]([O:45][C:46]1[CH:51]=[C:50]([N:16]2[C:17]3[C:22](=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:14]([C:10]3[CH:9]=[C:8]([CH3:40])[C:7]([OH:6])=[C:12]([CH3:13])[CH:11]=3)([C:24]3[CH:29]=[C:28]([CH3:30])[C:27]([OH:31])=[C:26]([CH3:39])[CH:25]=3)[C:15]2=[O:23])[CH:49]=[CH:48][CH:47]=1)[CH3:44]
Reactant: Cc1cc(C2(c3cc(C)c(O[Si](C)(C)C(C)(C)C)c(C)c3)C(=O)Nc3ccccc32)cc(C)c1O[Si](C)(C)C(C)(C)C
Reactant: CCOc1cccc(B(O)O)c1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Solvent: ClCCl
Product: CCOc1cccc(N2C(=O)C(c3cc(C)c(O)c(C)c3)(c3cc(C)c(O)c(C)c3)c3ccccc32)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 62.2 %

Procedure:
Combine 3,3-Bis-[4-(tert-butyl-dimethyl-silanyloxy)-3,5-dimethyl-phenyl]-1,3-dihydro-indol-2-one (0.500 g, 0.831 mmol), 3-ethoxyphenylboronic acid (0.276 g, 1.66 mmol), copper (II) acetate (0.151 g, 0.831 mmol), triethylamine (0.23 mL, 1.66 mmol), 4 angstrom molecular sieves, and dichloromethane (20 mL). Stir at room temperature overnight under ambient atmosphere. Filter the reaction through Celite. Elute through a column of silica gel with 70% dichloromethane in hexanes and concentrate. Dissolve the resulting compound (0.603 g, 0.83 mmol), in THF (4 mL). Add a solution of tetrabutylammonium fluoride (1.0M) in THF (2.1 mL). Stir for 1 h. Quench with saturated aqueous ammonium chloride(10 mL), water (40 mL) and ethyl acetate (50 mL). Separate the layers and concentrate the organic layer in vacuo. Chromatograph on silica gel eluting with 25% to 50% ethyl acetate in hexanes to give 0.255 g (62%) of the title compound: mass spectrum (ion spray): m/z=494(M+1); 1H NMR(DMSO-d6); δ8.28 (s, 2H), 7.51 (t, 1H), 7.37 (d, 1H), 7.29 (td, 1H), 7.16 (td, 1h), 7.08-7.06 (m, 1H), 7.02-6.98 (m, 2H), 6.87 (d, 1H), 6.80 (s, 4H), 4.12 (q, 2H), 2.12(s, 12H), 1.38 (t, 3H).
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][N:16]1C(=O)C2=CC=CC=C2C1=O.O.NN>CO>[NH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][OH:1]
Reactant: O=C1c2ccccc2C(=O)N1CCCCCCCCCCCCCCO
Agent: NN
Solvent: CO
Solvent: O
Product: NCCCCCCCCCCCCCCO

Procedure:
To a suspension of N-(14-hydroxytetradecyl)phthalimide in 100 ml of methanol was added 0.87 g of hydrazine monohydrate and the mixture was heated under reflux for 3 hours. The reaction solution was distilled under reduced pressure and the residue was diluted with a 1N aqueous solution of sodium hydroxide and then extracted twice with chloroform. The organic layers were combined, washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate and then distilled under reduced pressure. Chromatography over silica gel afforded the title compound as a colorless crystal.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:8]=[CH:9][CH:10]=1)[NH2:7])([O-:3])=[O:2].[CH3:11][S:12](Cl)(=[O:14])=[O:13].Cl>N1C=CC=CC=1>[CH3:11][S:12]([NH:7][C:6]1[CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:10]=[CH:9][CH:8]=1)(=[O:14])=[O:13]
Reactant: CS(=O)(=O)Cl
Reactant: Nc1cccc([N+](=O)[O-])c1
Agent: Cl
Solvent: c1ccncc1
Product: CS(=O)(=O)Nc1cccc([N+](=O)[O-])c1

Procedure:
To a solution of 2.76 g. (0.02 mol) of m-nitroaniline in 5 ml. of pyridine cooled to 0° C. is added 1.6 ml. (0.02 mol) of methanesulfonyl chloride dropwise and the mixture is stirred at room temperature for two hours. The reaction mixture is decomposed by addition of dilute hydrochloric acid and ice, and dried to give m-(methylsulfonamido)-nitrobenzene, m.p. 237° C. The latter, 1.08 g. (0.005 mol), is dissolved in 100 ml. of ethanol, 300 mg. of 10% palladium-on-carbon is added and the mixture is hydrogenated in a Parr shaker. After hydrogen uptake has ceased, the catalyst is filtered off leaving the product, 3-methylsulfonamidoaniline, in solution. To this solution (100 ml. ethanol) is added 1.08 g. (0.005 mol) of 3,5-diacetyl-4,6-dihydroxy-2H-pyran-2-one and the solution is refluxed for one hour. The reaction mixture is concentrated and filtered to yield 5-acetyl-4-hydroxy-3-[1-(3-methylsulfonamidophenylamino)ethylidene]-2H-pyran-2,6(3H)-dione, m.p. 196° C.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]2[C:8]([CH2:11][NH:12][C@@H:13]([CH3:21])[CH:14]([O:18][CH2:19][CH3:20])[O:15][CH2:16][CH3:17])=[CH:9][S:10][C:5]2=[CH:4][CH:3]=1.[CH:22]1[C:34]2[CH:33]([CH2:35][O:36][C:37]([NH:39][C@@H:40]([CH2:44][C:45]3[CH:50]=[CH:49][C:48]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[CH:47][CH:46]=3)[C:41](O)=[O:42])=[O:38])[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[C:26]=2[CH:25]=[CH:24][CH:23]=1>>[C:52]([O:51][C:48]1[CH:47]=[CH:46][C:45]([CH2:44][C@H:40]([NH:39][C:37](=[O:38])[O:36][CH2:35][CH:33]2[C:34]3[CH:22]=[CH:23][CH:24]=[CH:25][C:26]=3[C:27]3[C:32]2=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:41]([N:12]([CH2:11][C:8]2[C:6]3=[N:7][C:2]([Cl:1])=[CH:3][CH:4]=[C:5]3[S:10][CH:9]=2)[C@@H:13]([CH3:21])[CH:14]([O:18][CH2:19][CH3:20])[O:15][CH2:16][CH3:17])=[O:42])=[CH:50][CH:49]=1)([CH3:55])([CH3:53])[CH3:54]
Reactant: CCOC(OCC)[C@H](C)NCc1csc2ccc(Cl)nc12
Reactant: CC(C)(C)Oc1ccc(C[C@H](NC(=O)OCC2c3ccccc3-c3ccccc32)C(=O)O)cc1
Product: CCOC(OCC)[C@H](C)N(Cc1csc2ccc(Cl)nc12)C(=O)[C@H](Cc1ccc(OC(C)(C)C)cc1)NC(=O)OCC1c2ccccc2-c2ccccc21

Procedure:
According to the procedure described in the synthesis method of Compound III-1, (S)—N-((5-chlorothieno[3,2-b]pyridin-3-yl)methyl)-1,1-diethoxypropan-2-amine (Compound IX-7) 996 mg (3.03 mmol) was coupled with (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-3-(4-tert-butoxyphenyl)propanoic acid
Reaction SMILES: [CH3:1][C:2]1([CH3:11])[C:4]([CH3:6])([CH3:5])[CH:3]1[NH:7][C:8]([NH2:10])=[S:9].C([O:14][C:15](=O)[CH:16](Br)[CH:17]([CH3:19])[CH3:18])C>>[CH:17]([CH:16]1[S:9][C:8]([NH:7][CH:3]2[C:4]([CH3:5])([CH3:6])[C:2]2([CH3:11])[CH3:1])=[N:10][C:15]1=[O:14])([CH3:19])[CH3:18]
Reactant: CC1(C)C(NC(N)=S)C1(C)C
Reactant: CCOC(=O)C(Br)C(C)C
Product: CC(C)C1SC(NC2C(C)(C)C2(C)C)=NC1=O

Procedure:
Synthesis was performed from N-(2,2,3,3-tetramethylcyclopropyl)thiourea and ethyl-2-bromoisovalerate according to Method C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C@H:9]2[CH2:13][CH2:12][CH2:11][C@H:10]2[N:14]2C(=O)C3C(=CC=CC=3)C2=O)[CH:6]=[CH:7][CH:8]=1.NN>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C@H:9]2[CH2:13][CH2:12][CH2:11][C@H:10]2[NH2:14])[CH:6]=[CH:7][CH:8]=1
Reactant: COc1cccc([C@H]2CCC[C@H]2N2C(=O)c3ccccc3C2=O)c1
Agent: NN
Solvent: Cc1ccccc1
Product: COc1cccc([C@H]2CCC[C@H]2N)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of cis 2-[2-(3-methoxyphenyl)cyclopentyl]-1H-isoindole-1,3(2H)-dione (0.23 g, 0.72 mmol) in toluene (3 mL) was added hydrazine (0.23 mL, 7.23 mmol). After stirring at room temperature for 1 h, then 95° C. for 4 h, a precipitate formed. The mixture was cooled to rt, filtered, and washed with toluene. The filtrate was concentrated to give the desired product, which was used without further purification.
Reaction SMILES: [O:1]=[C:2]([CH:4]=[C:5]([CH3:7])[CH3:6])[CH3:3].[C:8]([O:12][OH:13])([CH3:11])([CH3:10])[CH3:9]>>[CH3:6][C:5]([O:13][O:12][C:8]([CH3:11])([CH3:10])[CH3:9])([CH2:4][C:2](=[O:1])[CH3:3])[CH3:7]
Reactant: CC(C)(C)OO
Reactant: CC(=O)C=C(C)C
Product: CC(=O)CC(C)(C)OOC(C)(C)C

Procedure:
Assay of the product by GLC indicated 76% product, 17% mesityl oxide, and 1% t-butyl hydroperoxide. The actual yield of product based on the t-butyl hydroperoxide consumed was 82%. Purification of product for GLC standard was accomplished by a double distillation under reduced pressure with a pot temperature of 40°±2° C. Fractions were collected and assayed. Micro analysis found: C, 64.10%; H, 11.10%; O, 24,96%. Calculated: C, 63.79; H, 10.71; O, 25.49; SN-7-249-95. cuts 5, 6, and 7 nD25 1.4170, cuts 1, 2, 3, 4 nD25 1.4167, 1.4167, 1.4167, 1.4169 respectively. Reference IR spectrum R-IR#6.
Reaction SMILES: F[B-](F)(F)F.[CH3:6][O+](C)C.ClCCl.[Si:13]([O:30][CH2:31][C:32]1[N:33]=[C:34]([N:44]2[CH2:49][CH2:48][N:47]([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:46][CH2:45]2)[N:35]([CH2:40][C:41]#[C:42][CH3:43])[C:36]=1[C:37](=[S:39])[NH2:38])([C:26]([CH3:29])([CH3:28])[CH3:27])([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C(OCC)(=O)C>[Si:13]([O:30][CH2:31][C:32]1[N:33]=[C:34]([N:44]2[CH2:49][CH2:48][N:47]([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:46][CH2:45]2)[N:35]([CH2:40][C:41]#[C:42][CH3:43])[C:36]=1[C:37]([S:39][CH3:6])=[NH:38])([C:26]([CH3:28])([CH3:27])[CH3:29])([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: C[O+](C)C
Reactant: CC#CCn1c(N2CCN(C(=O)OC(C)(C)C)CC2)nc(CO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)c1C(N)=S
Agent: F[B-](F)(F)F
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CC#CCn1c(N2CCN(C(=O)OC(C)(C)C)CC2)nc(CO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)c1C(=N)SC
Temperature: 25 °C
Reaction time: 15 h
Yield: 99.8 %

Procedure:
1.23 g of trimethyloxonium tetrafluoroborate was added to a 100 ml dichloromethane solution of 4.351 g of t-butyl 4-[4-(t-butyldiphenylsilanyloxymethyl)-1-(2-butynyl)-5-thiocarbamoyl-1H-imidazol-2-yl]piperazine-1-carboxylate, and the mixture was stirred at room temperature for 15 hours. 300 ml of ethyl acetate was added to the solution, and the organic layer was washed successively with 100 ml of a saturated sodium bicarbonate solution and 100 ml a saturated ammonium chloride solution. The organic layer was dried over magnesium sulfate, and concentrated under reduced pressure to give 4.439 g of the title compound.
Reaction SMILES: [CH:1]1([CH2:6][N:7]2[C:19]3[CH:18]=[CH:17][CH:16]=[C:15]([OH:20])[C:14]=3[C:13]3[C:8]2=[CH:9][CH:10]=[CH:11][C:12]=3[C:21]([O:23]C)=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH3:25]>C1COCC1.[OH-].[NH4+]>[CH:1]1([CH2:6][N:7]2[C:19]3[CH:18]=[CH:17][CH:16]=[C:15]([OH:20])[C:14]=3[C:13]3[C:8]2=[CH:9][CH:10]=[CH:11][C:12]=3[C:21](=[O:23])[NH2:25])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: N
Reactant: COC(=O)c1cccc2c1c1c(O)cccc1n2CC1CCCC1
Agent: [NH4+]
Agent: [OH-]
Solvent: C1CCOC1
Product: NC(=O)c1cccc2c1c1c(O)cccc1n2CC1CCCC1
Temperature: 35 °C

Procedure:
A solution of 9-[(cyclopentyl)methyl]-4-hydroxy-5-carbomethoxy carbazole (110 mg, 0.34 mmol) in 3 mL of THF and 20 mL of concentrated aqueous ammonium hydroxide was treated with a stream of NH3 gas to ensure saturation. The reaction vessel was capped, and the mixture heated to 35° C. with stirring until tlc indicated complete consumption of starting material (20 h). The THF was evaporated, and the aqueous layer was filtered. The resultant solid was triturated with ether to afford 50 mg (0.162; 48%) of the title compound as a greenish-white solid. IR (KBr, cm−1) 3416, 3199, 3126, 1630, 1599. 1442, 1262, 778. FAB HRMS m/e, Calcd for C20H21N2O2: 309.1603. Found: 309.1607 (M+1).’
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([N+:12]([O-])=O)=[C:7]([CH:11]=1)[C:8]([OH:10])=[O:9]>C1COCC1.[Pd]>[NH2:12][C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:11][C:7]=1[C:8]([OH:10])=[O:9]
Reactant: COc1ccc([N+](=O)[O-])c(C(=O)O)c1
Agent: [Pd]
Solvent: C1CCOC1
Product: COc1ccc(N)c(C(=O)O)c1
Reaction time: 18 h
Yield: 98.3 %

Procedure:
5-Methoxy-2-nitrobenzoic acid (30.0 g, 152.2 mmol) was hydrogenated over Pd/C (10% c, 300 mg) in THF (250 mL) at room temperature under H2 balloon. The mixture was stirred for 18 h. After the reaction was completed, the catalyst was removed by filtration over Celite and the filtrate was concentrated to afford 25.0 g of 2-amino-5-methoxybenzoic acid as a brown solid (98%). LCMS m/z=168.1 (M+1), 150.1 (M−17) (Method B) (retention time=0.53 min) 1H NMR (400 MHz, DMSO-d6): δ 7.31 (d, J=2.8 Hz, 1H), 6.61 (dd, J=8.8, 3.2 Hz, 1H), 6.44 (d, J=8.8 Hz, 1H), 3.60 (s, 3H).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([NH:15][C:16](=[O:20])OCC)=[N:5][C:6]2[C:11]([N:12]=1)=[CH:10][C:9]([O:13][CH3:14])=[CH:8][CH:7]=2.[N:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[N:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1>>[CH3:1][O:2][C:3]1[C:4]([NH:15][C:16]([N:30]2[CH2:31][CH2:32][N:27]([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][N:21]=3)[CH2:28][CH2:29]2)=[O:20])=[N:5][C:6]2[C:11]([N:12]=1)=[CH:10][C:9]([O:13][CH3:14])=[CH:8][CH:7]=2
Reactant: CCOC(=O)Nc1nc2ccc(OC)cc2nc1OC
Reactant: c1ccc(N2CCNCC2)nc1
Product: COc1ccc2nc(NC(=O)N3CCN(c4ccccn4)CC3)c(OC)nc2c1
Yield: 94 %

Procedure:
Ethyl N-(3,6-dimethoxyquinoxalin-2-yl)carbamate and 1-(2-pyridyl)piperazine were reacted by the same way with the example 148 to obtain the titled compound (yield, 94%).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:15]=[CH:14][C:13]3[NH:12][CH2:11][C@@H:10]4[CH2:16][C@H:17]([N:19]([CH2:23][CH2:24][CH3:25])[CH2:20][CH2:21][CH3:22])[CH2:18][C:8]=2[C:9]=34)[CH:2]=1.N1C2C(=CC=CC=2)C=C1.C1([Se](O[Se](C2C=CC=CC=2)=O)=O)C=CC=CC=1>C1COCC1.O>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:15]=[CH:14][C:13]3[NH:12][CH:11]=[C:10]4[CH2:16][C@H:17]([N:19]([CH2:23][CH2:24][CH3:25])[CH2:20][CH2:21][CH3:22])[CH2:18][C:8]=2[C:9]=34)[CH:2]=1
Reactant: CCCN(CCC)[C@@H]1Cc2c(-c3cccnc3)ccc3c2[C@H](CN3)C1
Agent: O=[Se](O[Se](=O)c1ccccc1)c1ccccc1
Agent: c1ccc2[nH]ccc2c1
Solvent: C1CCOC1
Solvent: O
Product: CCCN(CCC)[C@H]1Cc2c[nH]c3ccc(-c4cccnc4)c(c23)C1
Temperature: 25 °C
Yield: 53.2 %

Procedure:
A solution of 1.0 g (2.99 mmol) of (2aR,4S)-6-(3-pyridyl)-4-(di-n-propylamino)-1,2,2a,3,4,5-hexahydrobenz [cd]indole and 1.0 g (9 mmol) of indole in 50 ml of THF was treated at 0°C. with 0.61 g (1.70 mmol) of benzeneseleninic anhydride. The resulting solution was allowed to warm to room temperature. After 2 hours the reaction solution was diluted with water and the product was extracted into methylene chloride. The methylene chloride was evaporated and the resulting residue was taken up in aqueous tartaric acid. This acidic solution was washed with methylene chloride, then basified with 5M sodium hydroxide solution. The product was extracted into methylene chloride. After evaporating the methylene chloride the product was chromatographed over 25 g of silica gel using 10% ethyl acetate in toluene followed by 1:1 ethyl acetate/toluene as eluent. The material from the column was crystallized from toluene/hexane to afford 0.53 g of title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4](/[C:12](=[N:16]\[O:17][CH:18]([CH3:20])[CH3:19])/[C:13]([OH:15])=O)[CH:5]=[CH:6][C:7]=1[S:8]([CH3:11])(=[O:10])=[O:9].[C:21]([O:25][C:26]([N:28]1[C:32]([NH2:33])=[CH:31][CH:30]=[N:29]1)=[O:27])([CH3:24])([CH3:23])[CH3:22].C(N(CC)C(C)C)(C)C>C(#N)C>[C:21]([O:25][C:26]([N:28]1[C:32]([NH:33][C:13](=[O:15])/[C:12](/[C:4]2[CH:5]=[CH:6][C:7]([S:8]([CH3:11])(=[O:9])=[O:10])=[C:2]([Cl:1])[CH:3]=2)=[N:16]/[O:17][CH:18]([CH3:20])[CH3:19])=[CH:31][CH:30]=[N:29]1)=[O:27])([CH3:24])([CH3:22])[CH3:23]
Reactant: CC(C)O/N=C(/C(=O)O)c1ccc(S(C)(=O)=O)c(Cl)c1
Reactant: CC(C)(C)OC(=O)n1nccc1N
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: CC(C)O/N=C(/C(=O)Nc1ccnn1C(=O)OC(C)(C)C)c1ccc(S(C)(=O)=O)c(Cl)c1
Reaction time: 2 h
Yield: 20 %

Procedure:
The estimated 80% pure (E)-(3-chloro-4-methanesulfonyl-phenyl)-isopropoxyimino-acetic acid and (prepared as in Example 6, 99 mg, 0.31 mmol), 5-amino-pyrazole-1-carboxylic acid tert-butyl ester (625 mg, 0.34 mmol) and N,N-diisopropylethylamine (162 μL, 0.93 mmol) were combined in acetonitrile (1.25 mL) and cooled in an ice bath. O-(7-Azabenzotriazole-1-yl)-N,N,N′N′-tetramethyluronium hexafluorophosphate (118 mg, 0.31 mmol) was added and the ice bath was removed. After stirring 2 h, the reaction mixture was evaporated in vacuo. The residue was treated with saturated aqueous sodium bicarbonate solution (1 mL) and extracted with chloroform (2×3 mL). The combined organic phases were dried over sodium sulfate and evaporated in vacuo. The residue was purified by flash column chromatography (Merck silica gel 60, 40-63 μm; 60% ethyl acetate/hexanes) to afford (E)-5-[2-(3-chloro-4-methanesulfonyl-phenyl)-2-isopropoxyimino-acetylamino]-pyrazole-1-carboxylic acid tert-butyl ester (30 mg, 20%) as a tan solid after lyophilization from aqueous acetonitrile: H1-NMR (400 MHz, CDCl3) δ=1.41 (6H, d, J=6.3 Hz), 1.72 (9H, s), 3.30 (3H, s), 4.66 (1H, m), 6.85 (1H, d, J=1.8 Hz), 7.60 (2H, m), 7.70 (1H, d, J=1.5 Hz), 8.20 (1H, d, J=8.0 Hz), 11.64 (1H, s).
Reaction SMILES: [CH2:1]([NH:5][C:6]([NH:8][CH2:9][CH2:10][Cl:11])=[O:7])[CH:2]([CH3:4])[CH3:3].C(O)C.[N:15]([O-])=[O:16].[Na+]>Cl.O>[CH2:1]([NH:5][C:6]([N:8]([CH2:9][CH2:10][Cl:11])[N:15]=[O:16])=[O:7])[CH:2]([CH3:4])[CH3:3]
Reactant: CC(C)CNC(=O)NCCCl
Reactant: O=N[O-]
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CC(C)CNC(=O)N(CCCl)N=O
Reaction time: 2 h
Yield: 70 %

Procedure:
A 2 g (11.2 mmol) quantity of 1-isobutyl-3-(2-chloroethyl) urea was dissolved in 25 ml of concentrated HCl:ethanol, 2:1, and cooled to 5° C. A solution of 773 mg (11.2 mmol) of sodium nitrite in 5 ml of water was added in portions and the mixture was stirred at this temperature for 2 hrs. The crystalline yellow solid was filtered and dried in vacuo overnight giving 1.6 g (70%) of the product, MP 51° C. (decomposes). IR analysis showed peaks at 1705/cm (C=O) and 1525/cm (C--N=O). NMR: Doublet (6H, J=6.8 Hz) at 0.9 ppm, multiplet (1H) at 2.0 ppm, multiplet (6H) at 3.7 ppm.