Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Li]CCCC.[Cl:6][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14](C(C3C(C)=NC(C)=CC=3)O)[CH:15]=2)[N:10]=[C:9]([O:27][CH3:28])[C:8]=1[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][CH:31]=1.[CH3:40][N:41]1[C:45]([C:46]([C:48]2[CH:49]=[N:50][C:51]([C:54]([F:57])([F:56])[F:55])=[CH:52][CH:53]=2)=[O:47])=[CH:44][N:43]=[N:42]1>C1COCC1>[Cl:6][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:46]([C:45]3[N:41]([CH3:40])[N:42]=[N:43][CH:44]=3)([C:48]3[CH:49]=[N:50][C:51]([C:54]([F:55])([F:57])[F:56])=[CH:52][CH:53]=3)[OH:47])[CH:15]=2)[N:10]=[C:9]([O:27][CH3:28])[C:8]=1[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:37])[F:38])=[CH:32][CH:31]=1
Reactant: Cn1nncc1C(=O)c1ccc(C(F)(F)F)nc1
Reactant: COc1nc2ccc(C(O)c3ccc(C)nc3C)cc2c(Cl)c1Cc1ccc(C(F)(F)F)cc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: COc1nc2ccc(C(O)(c3ccc(C(F)(F)F)nc3)c3cnnn3C)cc2c(Cl)c1Cc1ccc(C(F)(F)F)cc1
Temperature: -78 °C
Reaction time: 0.17 h

Procedure:
A solution of n-BuLi (2.5 M in hexanes, 1.85 mL, 4.62 mmol) was added dropwise by syringe to a mixture of 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (0.31 g, 0.72 mmol, Intermediate 12: step d) and (1-methyl-1H-1,2,3-triazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone (0.29 g, 1.16 mmol, Intermediate 53: step b) in dry THF (8 mL) at −78° C. over a three minute period. The mixture was stirred at −78° C. for 10 minutes then was immersed in an ice H2O bath and stirred at 0° C. for 1 hour. The solution was quenched with saturated aqueous NaHCO3, warmed to room temperature, and the layers were separated. The aqueous layer was further extracted with EtOAc and the organic extracts were washed with brine, dried over Na2SO4, filtered and evaporated in vacuo. The residue was purified by FCC [(30% EtOH in EtOAc)/heptane, gradient] to provide the title compound. MS (ESI) 608 [M+H]+.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][C:6](=[O:13])/[C:5]/2=[CH:14]\[NH:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]2[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]2)=[CH:18][CH:17]=1.[N+:29](C1C=C2C(=CC=1)C(=O)NC(=O)C2)([O-:31])=[O:30].CN1CCN(CC2C=CC(N)=CC=2)CC1.C(OCC)(OCC)OCC>C(O)CO>[N+:29]([C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[NH:7][C:6](=[O:13])/[C:5]/2=[CH:14]\[NH:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]2[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]2)=[CH:18][CH:17]=1)([O-:31])=[O:30]
Reactant: O=C1Cc2cc([N+](=O)[O-])ccc2C(=O)N1
Reactant: CN1CCN(c2ccc(N/C=C3\C(=O)NC(=O)c4ccc(Br)cc43)cc2)CC1
Agent: CN1CCN(Cc2ccc(N)cc2)CC1
Solvent: CCOC(OCC)OCC
Solvent: OCCO
Product: CN1CCN(c2ccc(N/C=C3\C(=O)NC(=O)c4ccc([N+](=O)[O-])cc43)cc2)CC1
Yield: 32 %

Procedure:
Using the procedure described for (4Z)-6-bromo-4-({[4-(4-methylpiperazin-1-yl)phenyl}amino}methylene)isoquinoline-1,3(2H,4H)-dione (Example 27), 0.21 g (1.0 mmol) of 6-nitroisoquinoline-1,3(2H,4H)-dione, 0.20 g of 4-(4-methylpiperazin-1-yl)methyl-phenylamine, 0.18 ml (1.1 mmol) of triethyl orthoformate, and 2.0 ml of ethylene glycol were reacted to give 0.13 g (32%) of amber solid, mp 250-2600 (dec); MS (ES+) m/z 408.2 (M+H)+1
Reaction SMILES: C[O-].[Na+].CO.[CH3:6][NH:7][C:8]1[C:13]([CH:14]=[CH:15][C:16](OCCCC)=[O:17])=[CH:12][C:11]([N+:23]([O-:25])=[O:24])=[CH:10][N:9]=1>O>[CH3:6][N:7]1[C:8]2[C:13](=[CH:12][C:11]([N+:23]([O-:25])=[O:24])=[CH:10][N:9]=2)[CH:14]=[CH:15][C:16]1=[O:17]
Reactant: CCCCOC(=O)C=Cc1cc([N+](=O)[O-])cnc1NC
Agent: C[O-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: Cn1c(=O)ccc2cc([N+](=O)[O-])cnc21
Yield: 76 %

Procedure:
5M sodium methoxide (methanol solution) (0.5 ml) was added to a methanol solution (2 ml) containing n-butyl 3-(2-(methylamino)-5-nitropyridin-3-yl)acrylate (43 mg) obtained in the 1st step, followed by reflux for 3.5 hours. Water was added to the reaction solution, followed by extraction with ethyl acetate. The resultant was washed with saturated saline and dried over anhydrous sodium sulfate. Subsequently, the solvent was distilled away under reduced pressure, the obtained residue was purified by silica gel chromatography (n-hexane:ethyl acetate=4:1 to 2:1), and a white solid of 1-methyl-6-nitro-1,8-naphthyridin-2(1H)-one (24 mg) was thus obtained.
Reaction SMILES: CO[C:3](=O)[C:4]1[C:9]([I:10])=[CH:8][CH:7]=[CH:6][C:5]=1[CH2:11]Br.[CH2:14]([NH2:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C([O-])([O-])=[O:23].[K+].[K+].C(OCC)(=O)C>C1(C)C=CC=CC=1.CCCCCC>[CH2:14]([N:21]1[CH2:3][C:4]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[I:10])[C:11]1=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: COC(=O)c1c(I)cccc1CBr
Reactant: O=C([O-])[O-]
Reactant: NCc1ccccc1
Agent: [K+]
Solvent: CCCCCC
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Product: O=C1c2cccc(I)c2CN1Cc1ccccc1
Temperature: 100 °C
Reaction time: 2 h
Yield: 46.5 %

Procedure:
A mixture of 2-bromomethyl-6-iodo-benzoic acid methyl ester (0.708 g, 2.0 mmol), benzylamine (0.218 mL, 2.0 mmol), and K2CO3 (0.69 g, 5.0 mmol) in toluene (6 mL) was heated with stirring at 100° C. for 2 h. Workup and silica gel column chromatography using 30% ethyl acetate in hexane afforded 2-benzyl-4-iodo-2,3-dihydro-isoindol-1-one (0.325 g, 47%). 1H NMR (300 MHz, CDCl3): δ (ppm) 4.18 (s, 2H), 4.84 (s, 2H), 7.21-7.38 (m, 6H), 7.86 (m, 2H). GC-MS: m/z 349 (M)+, 272 (M−77)+.
Reaction SMILES: [CH3:1][C:2]([NH2:5])([CH3:4])[CH3:3].C([O-])([O-])=O.[K+].[K+].[C:12]1([S:18](Cl)(=[O:20])=[O:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>C1COCC1.O>[C:2]([NH:5][S:18]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)(=[O:20])=[O:19])([CH3:4])([CH3:3])[CH3:1]
Reactant: CC(C)(C)N
Reactant: O=S(=O)(Cl)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(C)NS(=O)(=O)c1ccccc1
Reaction time: 8 h
Yield: 70.3 %

Procedure:
2-Methylpropan-2-amine (5.8 g, 80 mmol) and K2CO3 (11 g, 80 mmol) were dissolved in a mixed solvents of THF and H2O (V:V=1:5, 30 ml). Benzenesulfonyl chloride (7.06 g, 40.0 mmol) was added drop wise at 0° C. to the above solution. After being stirred overnight, the resulting mixture was extracted with ethyl acetate (3×100 mL), washed with 1 N HCl (50 mL), sat. NaHCO3 (50 mL), sat. NaCl (50 mL), and dried over Na2SO4. After concentration, the residue was purified by silica gel chromatography eluting with a 0-10% gradient of EtOAc in petroleum ether to afford N-tert-butylbenzenesulfonamide (6.0 g, 90% yield) as white solid. 1H NMR (500 MHz, CDCl3): δ 7.93-7.91 (m, 2H), 7.54-7.47 (m, 3H), 5.06 (br, 1H), 1.22 (s, 9H)
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([NH2:11])[N:8]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:7]=1)=[O:5])[CH3:2].Br[CH2:19][C:20](=[O:25])[C:21]([CH3:24])([CH3:23])[CH3:22].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([NH:11][CH2:19][C:20](=[O:25])[C:21]([CH3:24])([CH3:23])[CH3:22])[N:8]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:7]=1)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1cc(N)n(-c2ccccc2)n1
Reactant: CC(C)(C)C(=O)CBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CCOC(=O)c1cc(NCC(=O)C(C)(C)C)n(-c2ccccc2)n1
Temperature: 100 °C
Yield: 23.4 %

Procedure:
6 g (25.9 mmol) of 5-Amino-1-phenyl-1H-pyrazole-3-carboxylic acid ethyl ester are dissolved in 50 ml DMF, 4.65 g (25.9 mmol) 1-bromopinacolone and 16 g (49.1 mmol, 1.9 eq) of Cs2CO3 are added and the resulting mixture is heated to 100° C. for 4 hours. The reaction mixture is filtrated and the solvent removed in vacuo, the residue is subjected to preparative HPLC chromatography to obtain 2 g (23%) of the product.
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[CH:10]([O:12][C:13]1[CH:19]=[CH:18][C:16]([NH2:17])=[CH:15][CH:14]=1)[CH3:11].[S-:20][C:21]#[N:22].[K+].BrBr>>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[CH:10]([O:12][C:13]1[CH:14]=[CH:15][C:16]2[N:17]=[C:21]([NH2:22])[S:20][C:18]=2[CH:19]=1)[CH3:11]
Reactant: N#C[S-]
Reactant: CC(Oc1ccc(N)cc1)c1c(Cl)ccc(Cl)c1Cl
Agent: BrBr
Agent: [K+]
Product: CC(Oc1ccc2nc(N)sc2c1)c1c(Cl)ccc(Cl)c1Cl
Yield: 100 %

Procedure:
6-[1-(2,3,6-Trichlorophenyl)ethoxy]-1,3-benzothiazol-2-amine was prepared according to the method described in Example 20d but from 1.5 g of 4-[1-(2,3,6-trichlorophenyl)ethoxy]aniline, 1.84 g of potassium thiocyanate and 0.243 cm3 of dibromine. We obtain 1.77 g of 6-[1-(2,3,6-trichlorophenyl)ethoxy]-1,3-benzothiazol-2-amine in the form of an orange-coloured resin, which has the following characteristics:
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH:11]([NH2:14])[CH2:10][CH2:9]1)=O)(C)(C)C.F[C:16]1[CH:17]=[CH:18][C:19]([N+:26]([O-:28])=[O:27])=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:21]=1.C(=O)([O-])[O-].[K+].[K+].[Cl:35]CCl>CS(C)=O.C(OCC)C>[ClH:35].[N+:26]([C:19]1[CH:18]=[CH:17][C:16]([NH:14][CH:11]2[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]2)=[CH:21][C:20]=1[C:22]([F:23])([F:24])[F:25])([O-:28])=[O:27]
Reactant: ClCCl
Reactant: CC(C)(C)OC(=O)N1CCC(N)CC1
Reactant: O=[N+]([O-])c1ccc(F)cc1C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOCC
Solvent: CS(C)=O
Product: Cl
Product: O=[N+]([O-])c1ccc(NC2CCNCC2)cc1C(F)(F)F

Procedure:
A solution of 4-amino-piperidine-1-carboxylic acid tert-butyl ester (47.8 g; 0.23 mol), 5-fluoro-2-nitrobenzotrifluoride (50.0 g; 0.23 mol) and potassium carbonate (99.7 g; 0.69 mol) in dimethylsulfoxide (600 mL) is heated at 100° C. for 3.5 hours. The mixture is then diluted with dichloromethane (200 mL) and is washed aq. sat ammonium chloride (2×55 mL) and with brine (25 mL). The organic layer is then dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue obtained is then dissolved in a minimum volume of diethylether and petrol ether is added until precipitation is observed. The precipitate is filtered, washed with petrol ether (10 mL) and dried under high vacuum to afford the desired product (75.4 g; 0.19 mol). The product is dissolved in a 1 to 1 mixture of dichloromethane and trifluoroacetic acid (600 mL) and the resulting solution is stirred at room temperature until complete conversion is observed. A 4N aq. solution of sodium hydroxide is added until the pH of the aqueous layer reaches 8-9. The organic phase is separated, dried over sodium sulfate, filtered and concentrated under vacuum. The residue obtained is diluted in diethylether (200 mL) and a molar solution of hydrochloric acid in diethylether (150 mL) is added. The precipitate obtained is filtered and dried under high vacuum to afford the desired product as hydrochloride (59.0 g; 0.18 mol).
Reaction SMILES: [OH:1][CH:2]1[CH2:7][CH2:6][CH2:5][NH:4][CH2:3]1.C(N(CC)CC)C.[C:15](Cl)(=[O:17])[CH3:16]>C1COCC1.C(Cl)Cl>[OH:1][CH:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:15](=[O:17])[CH3:16])[CH2:3]1
Reactant: OC1CCCNC1
Reactant: CC(=O)Cl
Solvent: C1CCOC1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)N1CCCC(O)C1
Temperature: -78 °C
Yield: 83.1 %

Procedure:
3-Hydroxypiperidine (3.0 g, 30.0 mmol) was dissolved in THF (40 mL) and methylene chloride (40 mL). Triethylamine (7.47 g, 74.0 mmol) was added. The mixture was cooled to −78° C. and acetyl chloride (2.35 g, 30.0 mmol) was added drop wise. The mixture was warmed to r.t. and stirred under nitrogen for 1 about an hour. The solvents were removed under reduced pressure, and the resulting oil was purified using silica chromatography (2% methanol in ethyl acetate) to afford the title compound (3.57 g, 83%) as an oil.
Reaction SMILES: NC1NN=C(C)C=1C1SC2C([S:17](Cl)(=[O:19])=[O:18])=CC=C(F)C=2N=1.[F:22][C:23]1[C:28]2[N:29]=[C:30]([C:32]3[C:36]([CH3:37])=[N:35][NH:34][C:33]=3[NH2:38])[S:31][C:27]=2[CH:26]=[CH:25][CH:24]=1.[NH3:39]>C(O)C>[NH2:38][C:33]1[NH:34][N:35]=[C:36]([CH3:37])[C:32]=1[C:30]1[S:31][C:27]2[CH:26]=[C:25]([S:17]([NH2:39])(=[O:19])=[O:18])[CH:24]=[C:23]([F:22])[C:28]=2[N:29]=1
Reactant: Cc1n[nH]c(N)c1-c1nc2c(F)cccc2s1
Reactant: Cc1n[nH]c(N)c1-c1nc2c(F)ccc(S(=O)(=O)Cl)c2s1
Reactant: N
Solvent: CCO
Product: Cc1n[nH]c(N)c1-c1nc2c(F)cc(S(N)(=O)=O)cc2s1
Yield: 72 %

Procedure:
The title compound (280 mg) was prepared from crude 2-(5-amino-3-methyl-1H-pyrazol-4-yl)-4-fluorobenzothiazole-7-sulfonyl chloride, which had been derived from the chlorosulfonation of 320 mg of 4-(4-fluorobenzothiazol-2-yl)-5-methyl-2H-pyrazol-3-ylamine, and a solution of excess ammonia dissolved in ethanol. MS (m/z, ES+): 328.0 (M+1, 100%). Yield=72%.
Reaction SMILES: [I-:1].[Na+].Cl[CH2:4][C:5]1[N:6]=[C:7]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[O:8][C:9]=1[CH3:10]>CC(C)=O>[I:1][CH2:4][C:5]1[N:6]=[C:7]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[O:8][C:9]=1[CH3:10]
Reactant: COc1ccc(-c2nc(CCl)c(C)o2)cc1
Reactant: [I-]
Agent: [Na+]
Solvent: CC(C)=O
Product: COc1ccc(-c2nc(CI)c(C)o2)cc1

Procedure:
Together with 37.7 g of sodium iodide, 19.9 g of 4-chloromethyl-2-(4-methoxy-phenyl)-5-methyl-oxazole are, in 300 ml of acetone, heated at the boil under reflux for 2 hours. After cooling of the reaction mixture, the solvent was removed under reduced pressure and the residue dissolved in 300 ml of methyl tert-butyl ether, the mixture is washed three times with saturated Na2S2O3 solution and dried over MgSO4, and the solvent is then removed under reduced pressure. This gives 49.8 g of 4-Iodomethyl-2-(4-methoxyphenyl)-5-methyloxazole as a light-brown solid.
Reaction SMILES: C(N(CC)CC)C.[F:8][C:9]1[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=1[C@H:16]1[CH2:22][N:21]2[C:23]([CH2:26][C:27]([F:30])([F:29])[F:28])=[CH:24][N:25]=[C:20]2[C@H:19]([NH2:31])[CH2:18][CH2:17]1.Cl[C:33](OC1C=CC([N+]([O-])=O)=CC=1)=[O:34].[C:45]1([C:51]2[NH:52][C:53](=[O:62])[N:54]([CH:56]3[CH2:61][CH2:60][NH:59][CH2:58][CH2:57]3)[N:55]=2)[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1>[F:8][C:9]1[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=1[C@H:16]1[CH2:22][N:21]2[C:23]([CH2:26][C:27]([F:30])([F:28])[F:29])=[CH:24][N:25]=[C:20]2[C@H:19]([NH:31][C:33]([N:59]2[CH2:58][CH2:57][CH:56]([N:54]3[C:53](=[O:62])[NH:52][C:51]([C:45]4[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=4)=[N:55]3)[CH2:61][CH2:60]2)=[O:34])[CH2:18][CH2:17]1
Reactant: O=c1[nH]c(-c2ccccc2)nn1C1CCNCC1
Reactant: N[C@@H]1CC[C@@H](c2cccc(F)c2F)Cn2c(CC(F)(F)F)cnc21
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=C(N[C@@H]1CC[C@@H](c2cccc(F)c2F)Cn2c(CC(F)(F)F)cnc21)N1CCC(n2nc(-c3ccccc3)[nH]c2=O)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 39.7 %

Procedure:
Triethylamine (19 μL, 0.135 mmol) was added to a solution of the hydrochloride salt of (6S,9R)-6-(2,3-difluorophenyl)-3-(2,2,2-trifluoroethyl)-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepin-9-amine (18.8 mg, 0.045 mmol) and 4-nitrophenyl chloroformate (9.0 mg, 0.045 mmol) in tetrahydrofuran (2 mL) at 0° C. After 1 h, 5-phenyl-2-piperidin-4-yl-2,4-dihydro-3H-1,2,4-triazol-3-one (11 mg, 0.045 mmol) and triethylamine (19 μL, 0.135 mmol) were added and the mixture allowed to warm to ambient temperature. After 1 h, saturated aqueous sodium carbonate was added and the mixture was extracted with dichloromethane. The organic layer was washed with saturated aqueous sodium bicarbonate (3×), saturated brine, dried over sodium sulfate, filtered and concentrated. Purification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid) gave the title compound (11 mg). MS 616.2509 (M+1).
Reaction SMILES: CN(C=O)C.[H-].[Na+].[C:8]1([CH2:14][SH:15])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[NH2:16][C:17]1[N:25]=[C:24](Cl)[N:23]=[C:22]2[C:18]=1[N:19]=[CH:20][N:21]2[CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>[Cl-].[Na+].O>[NH2:16][C:17]1[N:25]=[C:24]([S:15][CH2:14][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:23]=[C:22]2[C:18]=1[N:19]=[CH:20][N:21]2[CH2:27][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1
Reactant: SCc1ccccc1
Reactant: Nc1nc(Cl)nc2c1ncn2Cc1ccccc1
Agent: [Cl-]
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: Nc1nc(SCc2ccccc2)nc2c1ncn2Cc1ccccc1
Temperature: 100 °C
Yield: 71.6 %

Procedure:
To DMF suspension (10 ml) containing sodium hydride (410 mg, 10 mmol, 60% in mineral oil) were added α-toluenethiol (1.7 ml, 14 mmol) and 6-amino-9-benzyl-2-chloropurine (100 mg, 0.39 mmol) in order. The mixture was stirred under heating at 100° C. for 4.5 hours. Brine was added thereto and the mixture was extracted with ethyl acetate. The organic layer was dried on magnesium sulfate, filtrated and the solvent in the filtrate was evaporated in vacuo. The residue was purified with silica gel chromatography (0.5% methanol/chloroform) to give the subject compound (97 mg, yield 73%).
Reaction SMILES: N1[CH:5]=[CH:4][CH:3]=[CH:2]1.[S:6]([O-])([O-])(=O)=[O:7].[Na+].[Na+]>>[O:7]1[CH:5]=[CH:4][CH:3]=[CH:2]1.[S:6]1[CH:5]=[CH:4][CH:3]=[CH:2]1
Reactant: c1cc[nH]c1
Reactant: O=S(=O)([O-])[O-]
Agent: [Na+]
Product: c1ccoc1
Product: c1ccsc1

Procedure:
However, at about the same time, a separate group attempted to coat stainless steel and mild steel by the electropolymerization of aniline, pyrrole, furan and thiophene. According to Troch-Nagels, et al., in J. of Appl. Electrochem., 22:756-764, 1992, attempts to coat mild steel with polyaniline in neutral and basic solutions of water and methanol at between 0.8-1.5 V/SCE yielded non-conductive brown films. In 20 vol. % methanol and 0.13 M sulfuric acid, no films were produced below 0.8 V/SCE and poor quality, black and powdery films were produced when the potential was above 1.4 V/SCE. Polyaniline films also were reported to have been produced from 0.3 M aniline solutions in 0.1 M nitric acid with electrode potentials cycling between about −0.5-+1.5 V/SCE, but the films were powdery and brittle. While better films were reported to have been made on mild steel from 0.5 M pyrrole in 0.08 M sodium sulfate at 0.8-1.4 V/SCE, adhesion was reported to have been poor. No suitable films were formed from either furan or thiophene. Troch-Nagels, et al. concluded that polyaniline films on mild steel did not meet the requirements for industrialization because they were brittle, did not allow anaphoretic painting and did not improve corrosion resistance. Polypyrrole films were discovered to be slightly better, but their adhesion was found to be poor and the films were brittle. Aluminum was not included in the work.
Reaction SMILES: C([O:3][C:4](=[O:26])[C:5]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][N:12]=2)[CH:8]=[C:7]([C:18]2[S:22][N:21]=[N:20][C:19]=2[CH:23]([CH3:25])[CH3:24])[CH:6]=1)C.[Li+].[OH-]>C1COCC1>[CH:23]([C:19]1[N:20]=[N:21][S:22][C:18]=1[C:7]1[CH:6]=[C:5]([CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][N:12]=2)[CH:8]=1)[C:4]([OH:26])=[O:3])([CH3:25])[CH3:24]
Reactant: CCOC(=O)c1cc(-c2ccc(C)cn2)cc(-c2snnc2C(C)C)c1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Product: Cc1ccc(-c2cc(C(=O)O)cc(-c3snnc3C(C)C)c2)nc1
Temperature: 0 °C
Reaction time: 16 h
Yield: 86.7 %

Procedure:
A mixture of 3-(4-isopropyl-[1,2,3] thiadiazol-5-yl)-5-(5-methyl-pyridin-2-yl)-benzoic acid ethyl ester (250 mg, 0.68 mmol) in 10 mL THF was cooled to 0° C., and LiOH (0.5 mL of 2N aqueous solution) was added. The reaction mixture was allowed to warm to room temperature and was stirred for 16 hours. The reaction mixture was concentrated under reduced pressure and the residue was acidified with 3N aqueous HCl to a pH of 6. The mixture was extracted with ethyl actetate, and the combined organic fractions were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure to give 200 mg of 3-(4-isopropyl-[1,2,3] thiadiazol-5-yl)-5-(5-methyl-pyridin-2-yl)-benzoic acid, MS (M+H)=340.
Reaction SMILES: [CH:1]1([C:4]2[CH:5]=[C:6](B3OC(C)(C)C(C)(C)O3)[CH:7]=[CH:8][CH:9]=2)[CH2:3][CH2:2]1.[Cl:19][C:20]1[CH:21]=[C:22]([CH2:26][N:27]2[CH:31]=[CH:30][N:29]=[C:28]2[CH3:32])[N:23]=[N:24][CH:25]=1>>[ClH:19].[CH:1]1([C:4]2[CH:5]=[C:6]([C:20]3[CH:21]=[C:22]([CH2:26][N:27]4[CH:31]=[CH:30][N:29]=[C:28]4[CH3:32])[N:23]=[N:24][CH:25]=3)[CH:7]=[CH:8][CH:9]=2)[CH2:2][CH2:3]1
Reactant: Cc1nccn1Cc1cc(Cl)cnn1
Reactant: CC1(C)OB(c2cccc(C3CC3)c2)OC1(C)C
Product: Cc1nccn1Cc1cc(-c2cccc(C3CC3)c2)cnn1
Product: Cl

Procedure:
The title compound, MS: m/e=291.3 (M+H+), was prepared from 2-(3-cyclopropyl-phenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane and 5-chloro-3-(2-methyl-imidazol-1-yl-methyl)-pyridazine.
Reaction SMILES: [N+:1]([C:4]1[CH:22]=[CH:21][C:7]([CH2:8][O:9][C:10]([N:12]2[CH2:19][C@H:18]([OH:20])[CH2:17][C@H:13]2[C:14]([OH:16])=[O:15])=[O:11])=[CH:6][CH:5]=1)([O-:3])=[O:2].[N+:23]([C:26]1[CH:33]=[CH:32][C:29]([CH2:30]Br)=[CH:28][CH:27]=1)([O-:25])=[O:24]>>[N+:23]([C:26]1[CH:33]=[CH:32][C:29]([CH2:30][O:15][C:14](=[O:16])[C@@H:13]2[CH2:17][C@@H:18]([OH:20])[CH2:19][N:12]2[C:10]([O:9][CH2:8][C:7]2[CH:21]=[CH:22][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)=[O:11])=[CH:28][CH:27]=1)([O-:25])=[O:24]
Reactant: O=C(O)[C@@H]1C[C@@H](O)CN1C(=O)OCc1ccc([N+](=O)[O-])cc1
Reactant: O=[N+]([O-])c1ccc(CBr)cc1
Product: O=C(OCc1ccc([N+](=O)[O-])cc1)[C@@H]1C[C@@H](O)CN1C(=O)OCc1ccc([N+](=O)[O-])cc1

Procedure:
In the same manner as described in Reference Example 1-2 but using 500 mg of trans-1-p-nitrobenzyloxycarbonyl-4-hydroxy-L-proline and 383 mg of p-nitrobenzyl bromide, trans-1-p-nitrobenzyloxycarbonyl-4-hydroxy-L-proline p-nitrobenzyl ester was obtained.
Reaction SMILES: [C:1]([C:9]1[CH:13]=[CH:12][NH:11][CH:10]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:14]OS(O)(=O)=O>[OH-].[K+]>[NH2:14][N:11]1[CH:12]=[CH:13][C:9]([C:1](=[O:8])[C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:10]1
Reactant: NOS(=O)(=O)O
Reactant: O=C(c1ccccc1)c1cc[nH]c1
Agent: [K+]
Agent: [OH-]
Product: Nn1ccc(C(=O)c2ccccc2)c1

Procedure:
A 3-benzoylpyrrole of the formula ##STR28## in potassium hydroxide or other suitable base is reacted with hydroxylamine-O-sulfonic acid to yield a 1-amino-3-benzoylpyrrole of the formula ##STR29## This reaction typically takes place in the presence of a suitable solvent such as dimethylformamide at a temperature of about 0° to 25° C. (or at room temperature) for 0.5 to 4 hours.
Reaction SMILES: [CH3:1][NH:2][CH2:3][CH2:4][CH2:5][N:6]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[CH2:14][CH2:13][C:12]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]1=2.Cl.[C:22](=[O:25])([O-])[O-:23].[K+].[K+].[CH2:28]([C:36](Cl)(Cl)Cl)[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]C>CN(C=O)C>[CH2:36]([O:23][C:22](=[O:25])[N:2]([CH2:3][CH2:4][CH2:5][N:6]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:12]=2[CH2:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]1=2)[CH3:1])[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]
Reactant: O=C([O-])[O-]
Reactant: CNCCCN1c2ccccc2CCc2ccccc21
Reactant: CCCCCCCCC(Cl)(Cl)Cl
Agent: Cl
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCCCCCCOC(=O)N(C)CCCN1c2ccccc2CCc2ccccc21
Temperature: 25 °C
Reaction time: 12 h
Yield: 28.7 %

Procedure:
Desipramine hydrochloride (1 equivalent, 0.3 gram) was added drop wise to a stirred solution of potassium carbonate (2.5 equivalents, 0.34 gram) in dry DMF at 0° C. Octyl chloroform (1.5 equivalents, 0.429 grams) which had been dissolved in dry DMF was added drop wise to this mixture and stirred for 12 hours at room temperature. The reaction mixture was quenched with water, extracted with ethyl acetate, the organic layer separated, washed with brine solution and dried over anhydrous sodium sulfate. The dried material was concentrated and purified by column chromatography to provide a pale yellow liquid (yield: 0.12 gram) and analyzed by HPLC (purity 95.3%) The FTIR, MS and 1H NMR spectra were consistent with the assigned structure with the empirical formula of C27H38N2O2.