Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=O)=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13].CN(C)C=O.C(Cl)(=O)C(Cl)=O.[NH2:26][C:27]1[S:31][N:30]=[C:29]([CH3:32])[C:28]=1[Cl:33]>ClC(Cl)C>[Cl:33][C:28]1[C:29]([CH3:32])=[N:30][S:31][C:27]=1[NH:26][C:9](=[O:11])[CH2:8][C:5]1[CH:6]=[CH:7][C:2]([OH:1])=[C:3]([N+:12]([O-:14])=[O:13])[CH:4]=1
Reactant: Cc1nsc(N)c1Cl
Reactant: O=C(O)Cc1ccc(O)c([N+](=O)[O-])c1
Agent: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Solvent: CC(Cl)Cl
Product: Cc1nsc(NC(=O)Cc2ccc(O)c([N+](=O)[O-])c2)c1Cl
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 89.1 %

Procedure:
4-Hydroxy-3-nitrophenylacetic acid (10 g, 0.05 mol) was suspended in dichloroethane (50 ml) and stirred at room temperature under a nitrogen atmosphere. N,N-Dimethylformamide (0.1 ml) was added followed by dropwise addition of oxalyl chloride (6.77 g, 0.05 mol) over 20 minutes. The mixture was stirred at room temperature for 25 minutes and then at 40° C. for 20 minutes. The reaction mixture was then heated under reflux while a solution of 5-amino-4-chloro-3-methylisotiazole (7.54 g, 0.05 mol) in dichloroethane (30 ml) was added over 30 minutes. The resultant pale orange suspension was stirred at reflux for 2 hours and then cooled to room temperature, to give a precipitate, which was collected by filtration and washed with dichloromethane. The solid was suspended in water (150 ml), treated with 10% (w/v) sodium hydroxide (50 ml) and the resulting red solution was washed with dichloromethane (2×50 ml). The combined washings were extracted with water (50 ml) and the combined aqueous layers were acidified to pH4-5 by addition of concentrated hydrochloric acid (approximately 10 ml). The resultant yellow suspension was filtered and the solid was washed with water and dried under suction to give N-(4-chloro-3-methyl-5-isothiazolyl)-4-hydrox-3-nitrophenylacetamide (14.6 g) as a yellow solid.
Reaction SMILES: [C:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[N:15]([CH:21]3[CH2:23][CH2:22]3)[N:16]=[CH:17][C:18]=2[CH2:19][OH:20])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]>C1COCC1.O=[Mn]=O>[C:1]([N:8]1[CH2:9][CH2:10][CH:11]([C:14]2[N:15]([CH:21]3[CH2:23][CH2:22]3)[N:16]=[CH:17][C:18]=2[CH:19]=[O:20])[CH2:12][CH2:13]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]
Reactant: CC(C)(C)OC(=O)N1CCC(c2c(CO)cnn2C2CC2)CC1
Agent: O=[Mn]=O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC(c2c(C=O)cnn2C2CC2)CC1
Yield: 70.7 %

Procedure:
The above acid (300 mg, 0.894 mmol) was dissolved in 5 mL of THF. To this solution was added 3.58 mL (3.58 mmol) of 1M borane in THF. After stirring for 5 h, the mixture was poured into 15 mL of 5% HCl. The solution was extracted with 200 mL of EtOAc, and the extract was washed with saturated NaHCO3 and brine, dried over MgSO4, filtered, concentrated, and chromatographed (10-100 EtOAc in hexanes) to give 120 mg of N-Boc-4-(2-cyclopropyl-4-hydroxymethyl-2H-pyrazol-3-yl)-piperidine. This alcohol (100 mg, 0.31 mmol) was stirred overnight in 10 mL of THF with 270 mg (3.1 mmol) of activated MnO2. The mixture was filtered and concentrated to provide 70 mg of N-Boc-4-(2-cyclopropyl-4-formyl-2H-pyrazol-3-yl)-piperidine.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[C:9]2[C:19]2[CH:24]=[CH:23][C:22](/[CH:25]=[CH:26]/[N:27](C)C)=[C:21]([N+]([O-])=O)[CH:20]=2)=[CH:4][CH:3]=1>CCO.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[C:9]2[C:19]2[CH:24]=[C:23]3[C:22]([CH:25]=[CH:26][NH:27]3)=[CH:21][CH:20]=2)=[CH:6][CH:7]=1
Reactant: CN(C)/C=C/c1ccc(-c2nc3ccccc3c(=O)n2-c2ccc(Cl)cc2)cc1[N+](=O)[O-]
Solvent: CN(C)C=O
Solvent: CCO
Product: O=c1c2ccccc2nc(-c2ccc3cc[nH]c3c2)n1-c1ccc(Cl)cc1
Yield: 37.2 %

Procedure:
A solution of (E)-3-(4-chlorophenyl)-2-(4-(2-(dimethylamino)vinyl)-3-nitrophenyl)quinazolin-4(3H)-one (0.340 g, 0.76 mmol) in a 3:1 mixture of EtOH/DMF (50 mL) was flushed with N2. Pd/C (0.034 g, 10 wt %) was added the reaction was flushed with H2 for 1.5 hours. After filtering through diatomaceous earth, the filtrate was concentrated. Purification by flash chromatography on silica gel, eluting with 5% to 70% EtOAc in heptane, afforded the title compound as a white solid (0.105 g, 37%). 1H-NMR (300 MHz, DMSO-d6, mixture of rotamers): δ11.34 (s, 0.5H), 11.25 (s, 0.5H), 8.16-8.29 (m, 1H), 7.86-8.00 (m, 1H), 7.71-7.82 (m, 1H), 7.49-7.67 (m, 3H), 7.29-7.48 (m, 5H), 6.87-7.05 (m, 1H), 6.37-6.42 (m, 0.5H), 6.25-6.26 (m, 0.5H). MS (APCI) m/z: 372 (M+H)+.
Reaction SMILES: [N-]1C=CN=C1.CO.[C:8]([C:15]1NC=CN=1)([C:10]1NC=CN=1)=[O:9].ClCCl.[O:23]1[CH2:27][CH2:26][CH2:25][CH2:24]1>>[OH:9][C:8]1[CH:10]=[C:25]([CH:26]=[CH:27][CH:15]=1)[CH2:24][OH:23]
Reactant: O=C(c1ncc[nH]1)c1ncc[nH]1
Reactant: C1CCOC1
Agent: c1c[n-]cn1
Solvent: ClCCl
Solvent: CO
Product: OCc1cccc(O)c1

Procedure:
Scheme 20 Example 4 illustrates the preparation of carbamates in which an alkyloxycarbonylimidazole 20.8 is employed. In this procedure, a carbinol 20.5 is reacted with an equimolar amount of carbonyl diimidazole 20.11 to prepare the intermediate 20.8. The reaction is conducted in an aprotic organic solvent such as dichloromethane or tetrahydrofuran. The acyloxyimidazole 20.8 is then reacted with an equimolar amount of the amine R′NH2 to afford the carbamate 20.7. The reaction is performed in an aprotic organic solvent such as dichloromethane, as described in Tet. Lett., 42, 2001, 5227, to afford the carbamate 20.7.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:11]1[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]1.[O:18]1[C:22]([C:23](Cl)=[O:24])=[CH:21][CH:20]=[N:19]1>>[O:18]1[C:22]([C:23]([NH:1][C:2]2[CH:3]=[C:4]3[C:8](=[CH:9][CH:10]=2)[NH:7][CH:6]=[C:5]3[CH:11]2[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]2)=[O:24])=[CH:21][CH:20]=[N:19]1
Reactant: CN1CCC(c2c[nH]c3ccc(N)cc23)CC1
Reactant: O=C(Cl)c1ccno1
Product: CN1CCC(c2c[nH]c3ccc(NC(=O)c4ccno4)cc23)CC1
Yield: 57.3 %

Procedure:
Beginning with 13 mg (0.056 mMol) 5-amino-3-(1-methylpiperidin-4-yl)-1H-indole and 8.21 mg (0.062 mMol) isoxazole-5-carbonyl chloride, 10.4 mg (57%) of the title compound were recovered.
Reaction SMILES: [NH2:1][C:2]1[CH:28]=[CH:27][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]([N:16]3[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][N:24]([CH3:26])[CH3:25])[CH2:18][CH2:17]3)=[O:15])[CH:8]=2)=[CH:4][CH:3]=1.[C:29]1([CH2:35][C:36]([N:38]=[C:39]=[O:40])=[O:37])[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>O1CCCC1.CCCCCC>[CH3:26][N:24]([CH3:25])[CH2:23][CH2:22][N:19]1[CH2:18][CH2:17][N:16]([C:14]([NH:13][C:9]2[CH:8]=[C:7]([O:6][C:5]3[CH:4]=[CH:3][C:2]([NH:1][C:39]([NH:38][C:36](=[O:37])[CH2:35][C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)=[O:40])=[CH:28][CH:27]=3)[CH:12]=[CH:11][N:10]=2)=[O:15])[CH2:21][CH2:20]1
Reactant: O=C=NC(=O)Cc1ccccc1
Reactant: CN(C)CCN1CCN(C(=O)Nc2cc(Oc3ccc(N)cc3)ccn2)CC1
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CN(C)CCN1CCN(C(=O)Nc2cc(Oc3ccc(NC(=O)NC(=O)Cc4ccccc4)cc3)ccn2)CC1
Reaction time: 8 h
Yield: 72 %

Procedure:
To a solution of 4-(4-aminophenoxy)-2-{[4-(2-dimethylaminoethyl)piperazin-1-yl]carbonylamino}pyridine (97.2 mg) in tetrahydrofuran (5 ml) was added a solution of 2-phenylacetyl isocyanate in hexane (0.25 M, 2.6 ml) at room temperature, followed by stirring overnight. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=95:5) to provide the titled compound (100 mg, 72%) as white powder.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([C:13]1[CH:14]=[C:15]([CH2:19][C:20](O)=[O:21])[CH:16]=[N:17][CH:18]=1)[CH2:6][CH2:5]2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC.[NH:54]1[CH2:59][CH2:58][O:57][CH2:56][CH2:55]1>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([C:13]1[CH:18]=[N:17][CH:16]=[C:15]([CH2:19][C:20]([N:54]3[CH2:59][CH2:58][O:57][CH2:56][CH2:55]3)=[O:21])[CH:14]=1)[CH2:6][CH2:5]2
Reactant: O=C(O)Cc1cncc(N2CCc3cc(Cl)ccc3C2=O)c1
Reactant: C1COCCN1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(Cc1cncc(N2CCc3cc(Cl)ccc3C2=O)c1)N1CCOCC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 13.8 %

Procedure:
[5-(6-Chloro-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl)-pyridin-3-yl]-acetic acid (50 mg, 0.16 mmol), HATU (122 mg, 0.32 mmol), Et3N (64 mg, 0.64 mmol) and morpholine (56 mg, 0.64 mmol) were dissolved in DCM (4.0 mL) and the resulting reaction mixture was stirred at room temperature overnight. After evaporating off the DCM, the residue was re-dissolved in EtOAc and was washed with brine. The organic layer was dried over anhy. Na2SO4, filtered and concentrated in vacuo to give a crude product which was then purified by prep-HPLC to give the title compound (8.5 mg, 13.9%) as light yellow oil. MS: 386.1 (M+H+).
Reaction SMILES: CS[C:3]1[N:8]=[C:7]2[N:9]=[C:10]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[O:20][CH2:21][CH2:22][CH3:23])[NH:11][C:12](=[O:13])[C:6]2=[CH:5][N:4]=1.[CH:24]1([NH2:27])[CH2:26][CH2:25]1.C>C(O)C.[OH-].[Na+]>[CH:24]1([NH:27][C:3]2[N:8]=[C:7]3[N:9]=[C:10]([C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=4[O:20][CH2:21][CH2:22][CH3:23])[NH:11][C:12](=[O:13])[C:6]3=[CH:5][N:4]=2)[CH2:26][CH2:25]1
Reactant: CCCOc1ccccc1-c1nc2nc(SC)ncc2c(=O)[nH]1
Reactant: NC1CC1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CCCOc1ccccc1-c1nc2nc(NC3CC3)ncc2c(=O)[nH]1
Temperature: 90 °C
Reaction time: 18 h

Procedure:
A stirred mixture of 7-methylthio-4-oxo-2-(2-propoxyphenyl)-3,4-dihydropyrimido[4,5-d]pyrimidine (0.60 g) and cyclopropylamine (1.2 ml) in ethanol (20 ml) was heated for 18 hours at 90° C. in a pressure vessel. Further cyclopropylamine (1 ml) was added and the reaction mixture was stirred in a pressure vessel for 18 hours at 100° C. and then for 20 hours at 120° C. The cooled reaction mixture was evaporated under reduced pressure to yield a residue which was dissolved in 1 Normal sodium hydroxide. The resultant solution was treated with charcoal, filtered and the filtrate neutralised by the addition of concentrated hydrochloric acid which caused the precipitation of a crude product. The crude product was eluted from a silica column with chloroform as eluant, and the combined fractions containing product were evaporated under reduced pressure to yield a residue. This was twice recrystallised from methanol to yield the title compound, 0.23 g, m.p. 207.5°-208.5° C.
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][CH2:16][C:17]([OH:19])=[O:18].[CH3:20][S:21](Cl)(=[O:23])=[O:22]>N1C=CC=CC=1>[CH3:20][S:21]([O: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][CH2:16][C:17]([OH:19])=[O:18])(=[O:23])=[O:22]
Reactant: CS(=O)(=O)Cl
Reactant: O=C(O)CCCCCCCCCCCCCCCO
Solvent: c1ccncc1
Product: CS(=O)(=O)OCCCCCCCCCCCCCCCC(=O)O
Reaction time: 8 h

Procedure:
16-Hydroxyhexadecanoic acid (1 g) dissolved in a 10% hydrochloric acid-methanol solution was stirred at room temperature for 1 hour. The mixture was then concentrated and distributed into chloroform and water, and the chloroform layer was washed with a 1% aqueous sodium hydrogen carbonate solution and water, dried with anhydrous sodium sulfate and concentrated to give the methyl ester of 16-hydroxyhexadecanoic acid (1.02 g). To the methyl ester of 16-hydroxyhexadecanoic acid dissolved in pyridine (20 ml) was added methanesulfonyl chloride (0.50 g), and the mixture was stirred for 8 hours. Then, the pyridine was removed by distillation, and the residue was distributed into chloroform and water. The chloroform layer was dried with anhydrous sodium sulfate, concentrated and subjected to chromatography on a silica gel column with an eluent system of n-hexane-ethyl acetate (50:1) to give the methyl ester of 16-methanesulfonyloxy hexadecanoic acid (1.02 g).
Reaction SMILES: C([O:8][C@H:9]1[C@H:15]([O:16]CC2C=CC=CC=2)[C@@H:14]([O:24]CC2C=CC=CC=2)[C@:13]2([C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([CH2:40][C:41]4[CH:46]=[CH:45][C:44]([O:47][CH2:48][CH3:49])=[CH:43][CH:42]=4)[CH:34]=3)[O:32][C@@:10]1([CH:50]([OH:53])[CH2:51][OH:52])[CH2:11][O:12]2)C1C=CC=CC=1.ClC1C=CC=CC=1Cl>[Pd].CO.O1CCCC1>[Cl:39][C:36]1[CH:37]=[CH:38][C:33]([C@@:13]23[O:32][C@@:10]([CH:50]([OH:53])[CH2:51][OH:52])([CH2:11][O:12]2)[C@@H:9]([OH:8])[C@H:15]([OH:16])[C@H:14]3[OH:24])=[CH:34][C:35]=1[CH2:40][C:41]1[CH:42]=[CH:43][C:44]([O:47][CH2:48][CH3:49])=[CH:45][CH:46]=1
Reactant: CCOc1ccc(Cc2cc([C@]34OC[C@](C(O)CO)(O3)[C@@H](OCc3ccccc3)[C@H](OCc3ccccc3)[C@H]4OCc3ccccc3)ccc2Cl)cc1
Agent: [Pd]
Solvent: C1CCOC1
Solvent: Clc1ccccc1Cl
Solvent: CO
Product: CCOc1ccc(Cc2cc([C@]34OC[C@](C(O)CO)(O3)[C@@H](O)[C@H](O)[C@H]4O)ccc2Cl)cc1
Temperature: 25 °C
Reaction time: 5 h
Yield: 16.5 %

Procedure:
To a solution of 1-[(1R,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octan-1-yl]ethane-1,2-diol 7b (0.9 g, 1.22 mmol) in a methanol/tetrahydrofuran mixture (v/v=4/1, 15 mL) were added o-dichlorobenzene (0.82 mL, 6.1 mmol) and 10% Pd/C (36 mg, 0.12 mmol) in turn. The mixture was stirred at room temperature under H2 for 5 hours and filtered. The filter cake was washed with a methanol/tetrahydrofuran mixture (v/v=4/1, 10 mL×2). The combined filtrates were concentrated in vacuo. The residue was purified by prep-HPLC to give the title compound 7 as a white solid (94 mg, 9.43%, HPLC: 99.2%). The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 467.3[M+H]+; and 1H NMR (400 MHz, DMSO-d6) δ (ppm): 7.40 (m, 2H), 7.29 (dd, 1H), 7.09 (d, 2H), 6.83 (m, 2H), 5.27 (d, 1H), 4.95 (d, 1H), 4.89 (d, 1H), 4.88 (d, 1H), 4.55 (t, 1H), 4.00 (m, 5H), 3.66 (m, 3H), 3.45 (m, 2H), 3.37 (m, 2H), 1.30 (t, 3H).
Reaction SMILES: [S:1](Cl)([CH3:4])(=[O:3])=[O:2].[CH:6]1[C:16]2[CH:15]=[CH:14][C:13]3[CH:17]=[CH:18][CH:19]=[CH:20][C:12]=3[CH:11]([CH:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)[C:10]=2[CH:9]=[CH:8][CH:7]=1.C(N(CC)CC)C>C(Cl)Cl>[CH:17]1[C:13]2[CH:14]=[CH:15][C:16]3[CH:6]=[CH:7][CH:8]=[CH:9][C:10]=3[CH:11]([CH:21]3[CH2:22][CH2:23][N:24]([S:1]([CH3:4])(=[O:3])=[O:2])[CH2:25][CH2:26]3)[C:12]=2[CH:20]=[CH:19][CH:18]=1
Reactant: C1=Cc2ccccc2C(C2CCNCC2)c2ccccc21
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)N1CCC(C2c3ccccc3C=Cc3ccccc32)CC1

Procedure:
0.59 gram (5.17 millimoles) of mesyl chloride was added neat and in a dropwise manner over a 5 minute period to a stirred solution of 1.00 gram (3.62 millimoles) of 4-(5H-dibenzo[a,d]cyclohepten-5-yl)-piperidine and 1.45 grams (14.35 millimoles) of triethylamine in 10 milliliters of methylene chloride. The resulting solution was stirred an additional one-half hour and then diluted with 100 milliliters of methylene chloride. Thereafter the solution was washed with saturated sodium bicarbonate solution, then with brine and dried over magnesium sulfate. The drying agent was filtered off and the solvent vaporized in vacuo to obtain the desired 4-(5H-dibenzo[a,d]cyclohepten-5-yl)-1-(methylsulfonyl)piperidine product as a yellow solid residue. The product after recrystallization from ethyl acetate had a melting point of 260°-268° C. and elemental analyses as follows:
Reaction SMILES: [CH2:1]([NH2:5])[CH2:2][CH2:3][CH3:4].[C:6]([C@@H:11]([C@H:13]([C:15]([O:17]CC)=O)[OH:14])[OH:12])([O:8]CC)=O.O>CO>[CH2:1]([NH:5][C:6](=[O:8])[C@@H:11]([C@H:13]([C:15]([NH:5][CH2:1][CH2:2][CH2:3][CH3:4])=[O:17])[OH:14])[OH:12])[CH2:2][CH2:3][CH3:4]
Reactant: CCOC(=O)[C@H](O)[C@@H](O)C(=O)OCC
Reactant: CCCCN
Solvent: O
Solvent: CO
Product: CCCCNC(=O)[C@H](O)[C@@H](O)C(=O)NCCCC
Reaction time: 0.5 h
Yield: 56 %

Procedure:
N,N′-Di-n-butyl L-tartaramide was prepared by the reaction of n-butyl amine with diethyl L-tartrate. Diethyl L-tartrate (20.010 g, 1.0 eq) and HPLC grade methanol (40 mL) were weighed into a 250 mL round-bottomed flask equipped with a teflon coated magnetic stir bar. n-Butyl amine (14.906 g, 2.0 eq) was slowly poured into the stirring diethyl L-tartrate solution. Some fuming and a color change from water-white to pale yellow were observed. Additional methanol (10 mL) was used to rinse all of the amine into the reaction flask. After stirring the solution for 30 min, the flask was stoppered and refrigerated at approximately 45° F. (7° C.). The product crystallized out after 30 min of refrigeration; however, it was allowed to remain in the refrigerator for 3 days. The white needle-like crystals were filtered, washed with methanol (˜150 mL), washed with diethyl ether (2×30 mL), and dried under vacuum. The product was obtained in 56% yield (14.275 g, 54.8 mmole).
Reaction SMILES: [CH3:1][C:2]1[C:8]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[CH3:15])=[C:7]([S:16][CH3:17])[CH:6]=[CH:5][C:3]=1N.Cl.N([O-])=O.[Na+].[I-:23].[K+].S([O-])([O-])=O.[Na+].[Na+]>ClCCl.O>[I:23][C:3]1[CH:5]=[CH:6][C:7]([S:16][CH3:17])=[C:8]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[CH3:15])[C:2]=1[CH3:1]
Reactant: [I-]
Reactant: CSc1ccc(N)c(C)c1-c1ccccc1C
Agent: Cl
Agent: O=N[O-]
Agent: O=S([O-])[O-]
Solvent: ClCCl
Solvent: O
Product: CSc1ccc(I)c(C)c1-c1ccccc1C
Temperature: 5 °C
Reaction time: 1 h

Procedure:
A solution of 2.0 g (8.2 mmol) of 85 percent purity 2-methyl-3-(2-methylphenyl)-4-methylthioaniline in 3 mL of dichloromethane was combined with 60 mL of concentrated aqueous hydrochloric acid and the mixture was stirred for 1 hour. It was then cooled to 5° C. A solution of 850 mg (12 mmol) of sodium nitrite in 10 mL of water was added in portions with stirring and cooling. After 45 min, this mixture was poured with stirring into a mixture of a solution of 2.0 g (12 mmol) of potassium iodide in 100 mL of water and 75 mL of dichloromethane and the combination was stirred for 30 min. Five mL of saturated sodium sulfite solution was then added with stirring and after 20 min reaction time, the phases were separated. The organic phase was washed with water and with saturated aqueous sodium chloride solution, dried over sodium sulfate, and concentrated under reduced pressure. The 2.4 g (83 percent of theory) of oily residue obtained was the title compound in impure form.
Reaction SMILES: Cl[C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1.[N+:17]([C:20]1[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=1)([O-:19])=[O:18].C1N2CCN(CC2)C1.C(N(CC)CC)C>ClCCCl.C(Cl)Cl>[N+:17]([C:20]1[CH:25]=[CH:24][C:23]([O:26][C:2]2[N:10]=[CH:9][N:8]=[C:7]3[C:3]=2[N:4]=[CH:5][N:6]3[CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)=[CH:22][CH:21]=1)([O-:19])=[O:18]
Reactant: Clc1ncnc2c1ncn2C1CCCCO1
Reactant: O=[N+]([O-])c1ccc(O)cc1
Agent: C1CN2CCN1CC2
Solvent: ClCCCl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=[N+]([O-])c1ccc(Oc2ncnc3c2ncn3C2CCCCO2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 117.2 %

Procedure:
To a stirred slurry of 6-chloro-9-(tetrahydro-pyran-2-yl)-9H-purine (2.3 g, 10 mmol, 3 equiv) in anhydrous 1,2-dichloroethane (60 mL) was added a solution of 4-nitrophenol (2.3 g, 10 mmol, 3 equiv), DABCO (1.12 g, 1 mmol, 1 equiv) and triethylamine (3.03 g, 4.18 mL, 3 mmol, 3 equiv) in anhydrous 1,2-dichloroethane (5 mL). The mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with DCM (25 mL), washed with saturated solution of NaHCO3. The aqueous layer was re-extracted with DCM. The combined organic extracts were dried over MgSO4, filtered followed by solvent evaporation, giving 6-(4-nitro-phenoxy)-9-(tetrahydro-pyran-2-yl)-9H-purine (4 g, >99% yield). 1H NMR (400 MHz, CDCl3): δ 8.6 (s, 1H), 8.3 (m, 2H), 8.25 (s, 1H), 7.60 (m, 2H), 5.8 (m, 1H), 4.20 (m, 1H), 3.8 (m, 1H), 2.20 (m, 3H), 1.80 (m, 3H). MS (ESI) for C16H15N5O4: 342 (MH+).
Reaction SMILES: [F:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([OH:17])=[C:7]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:8]=[N:9]2)=[CH:4][CH:3]=1.[C:18](=O)([O-])[O-].[K+].[K+].S(OC)(OC)(=O)=O>CC(=O)CC>[F:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:17])[C:7]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:8][N:9]2[CH3:18])=[CH:4][CH:3]=1
Reactant: O=C([O-])[O-]
Reactant: CCOC(=O)c1cnc2cc(F)ccc2c1O
Agent: [K+]
Solvent: COS(=O)(=O)OC
Solvent: CCC(C)=O
Product: CCOC(=O)c1cn(C)c2cc(F)ccc2c1=O

Procedure:
A mixture of ethyl 7-fluoro-4-hydroxyquinoline-3-carboxylate (4.7 g), anhydrous potassium carbonate (3.0 g), dimethyl sulphate (2.52 g) and butanone (200 ml) can be boiled under reflux for 14 hours. The solvent can be evaporated and the residue can be triturated with dichloromethane (150 ml). The mixture can be filtered and the filtrate evaporated to a-small volume. Diethyl ether can be added, causing a solid to precipitate. The solid can be collected, washed with ether, dried and recrystallized from industrial methylated spirit to give the compound ethyl 7-fluoro-1-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylate, m.p. 164-166° C.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[C:7]1([C:13]2[O:14][CH:15]=[C:16]([CH2:18][O:19][C:20]3[CH:41]=[CH:40][C:23]([CH2:24][N:25]4[CH:29]=[C:28]([C:30](OCC)=[O:31])[C:27]([C:35]5[S:36][CH:37]=[CH:38][CH:39]=5)=[N:26]4)=[CH:22][CH:21]=3)[N:17]=2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.O.O.O.O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Na+].[Na+]>O1CCCC1>[C:7]1([C:13]2[O:14][CH:15]=[C:16]([CH2:18][O:19][C:20]3[CH:41]=[CH:40][C:23]([CH2:24][N:25]4[CH:29]=[C:28]([CH2:30][OH:31])[C:27]([C:35]5[S:36][CH:37]=[CH:38][CH:39]=5)=[N:26]4)=[CH:22][CH:21]=3)[N:17]=2)[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1
Reactant: CCOC(=O)c1cn(Cc2ccc(OCc3coc(-c4ccccc4)n3)cc2)nc1-c1cccs1
Agent: O=S(=O)([O-])[O-]
Agent: [Al+3]
Agent: [H-]
Solvent: O
Solvent: C1CCOC1
Product: OCc1cn(Cc2ccc(OCc3coc(-c4ccccc4)n3)cc2)nc1-c1cccs1
Reaction time: 0.5 h
Yield: 93.4 %

Procedure:
Lithium aluminium hydride (210 mg) was added portionwise to a solution of ethyl 1-[4-(2-phenyl-4-oxazolylmethoxy)benzyl]-3-(2-thienyl)-1H-pyrazole-4-carboxylate (2.73 g) in tetrahydrofuran (50 ml) at 0° C., which was stirred for 30 minutes. After sodium sulfate decahydrate (1.80 g) was added to the reaction mixture, and the precipitate was removed by filtration, the filtrate was concentrated. The residue was subjected to silica gel column chromatography to obtain [1-[4-(2-phenyl-4-oxazolylmethoxy)benzyl]-3-(2-thienyl)-1H-pyrazol-4-yl]methanol (2.33 g, yield: 94%) as colorless crystals from the fraction eluted with ethyl acetate-hexane (1:1, volume ratio). This was recrystallized from ethyl acetate-hexane. Melting point: 155˜156° C.
Reaction SMILES: [C:1]1([C:6]2[NH:7][C:8]3[C:13]([CH:14]=2)=[CH:12][CH:11]=[CH:10][CH:9]=3)[CH2:5][CH2:4][CH2:3][CH:2]=1.[C:15](/[CH:17]=[CH:18]\[C:19]([O:21][CH2:22][CH3:23])=[O:20])#[N:16]>CCOCC>[C:15]([CH:17]1[CH:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:14]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[NH:7][C:6]=2[C:1]2[CH2:5][CH2:4][CH2:3][C:2]1=2)#[N:16]
Reactant: CCOC(=O)/C=C\C#N
Reactant: C1=C(c2cc3ccccc3[nH]2)CCC1
Solvent: CCOCC
Product: CCOC(=O)C1c2c([nH]c3ccccc23)C2=C(CCC2)C1C#N
Yield: 8.3 %

Procedure:
2-(Cyclopenten-1-yl)indole (13.6 g, 74 mmol), ethyl cis-3-cyanoacrylate (17.8 g, 142 mmol) and BHT (70 mg) were heated to 180° C. under nitrogen for 30 min. The volatiles were removed by kugelrohr distillation at 110° C. and 0.8 mm to afford 19.7 g of an amber-brown tar. Addition of ether (50 mL) afforded a precipitate of a single isomer of white crystalline ethyl 4-cyano-1,2,3,4,5,10-hexahydrocyclopenta[a]carbazole-5-carboxylate (1.89 g, 8.2% yield); mp 192–195° C. NMR (CDCl3) δ 7.91 (s, 1H), 7.46 (d, 1H), 7.34 (d, 1H), 7.12 (m, 2H), 4.31 (d, 1H0, 4.32 (m, 2H), 4.20 (d, 1H), 3.46 (t, 1H), 3.30 (q, 1H), 2.80 (m, 1H), 2.3–1.4 (m, 6H), 1.34 (t, 3H). Anal. Calcd for C19H20N2O2: C, 74.00; H, 6.54; N, 9.08. Found: C, 73.84; H, 6.53; N, 9.03.