Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:20])([F:19])[C:3]1[CH:4]=[C:5]([C:9]2[CH:14]=[CH:13][C:12]([C@@H:15]3[CH2:17][C@H:16]3[NH2:18])=[CH:11][CH:10]=2)[CH:6]=[CH:7][CH:8]=1.[Cl:21][CH2:22][CH:23]=O>C(Cl)Cl>[Cl:21][CH2:22][CH2:23][NH:18][C@@H:16]1[CH2:17][C@H:15]1[C:12]1[CH:13]=[CH:14][C:9]([C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:19])([F:20])[F:1])[CH:4]=2)=[CH:10][CH:11]=1
Reactant: N[C@@H]1C[C@H]1c1ccc(-c2cccc(C(F)(F)F)c2)cc1
Reactant: O=CCCl
Solvent: ClCCl
Product: FC(F)(F)c1cccc(-c2ccc([C@@H]3C[C@H]3NCCCl)cc2)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 24.6 %

Procedure:
To a solution of (trans)-2-(3′-(trifluoromethyl)biphenyl-4-yl)cyclopropanamine (3.6 g, 38.26 mmol) in DCM (36 mL), 4° A molecular sieves was added followed by chloroacetaldehyde (5.8 mL, 38.26 mmol) and then stirred at RT for 1 h. After completion, monitored by TLC, cooled the reaction mixture at −10° C. and Na(CN)BH3 (2.88 g, 45.92 mmol) was added and stirred at RT for 2 h. After completion, the reaction mixture was quenched with NH4Cl (5%) and filtered through a pad of celite. The filtrate was extracted with DCM (2×50 mL), combined extracts were washed with water (40 mL), dried over anhydrous Na2SO4, filtered and evaporated. The residue was purified by flash column chromatography by using EtOAc: Pet ether to get (trans)-N-(2-chloroethyl)-2-(3′-(trifluoromethyl)biphenyl-4-yl)cyclopropanamine (3.2 g, 72.72%) as a liquid.
Reaction SMILES: [O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][CH:2]1[CH2:11][NH2:12].Cl[CH2:14][CH2:15][CH2:16][O:17][C:18]1[CH:27]=[CH:26][CH:25]=[C:24]2[C:19]=1[CH:20]=[CH:21][C:22](=[O:28])[NH:23]2.C(N(C(C)C)CC)(C)C.[I-].[Na+]>CN(C=O)C>[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3][CH:2]1[CH2:11][NH:12][CH2:14][CH2:15][CH2:16][O:17][C:18]1[CH:27]=[CH:26][CH:25]=[C:24]2[C:19]=1[CH:20]=[CH:21][C:22](=[O:28])[NH:23]2
Reactant: NCC1COc2ccccc2O1
Reactant: O=c1ccc2c(OCCCCl)cccc2[nH]1
Agent: [I-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: O=c1ccc2c(OCCCNCC3COc4ccccc4O3)cccc2[nH]1
Temperature: 80 °C
Yield: 11 %

Procedure:
2,3-Dihydro-1,4-benzodioxin-2-methanamine (0.56 g, 4.0 mmole), 5-(3-chloropropoxy)carbostyril (0.70 g, 3.1 mmole), diisopropylethylamine (0.65 g, 5.0 mmole) and sodium iodide (1.0 g, 6.5 mmole) were combined in 50 ml of DMF and heated at 80° C. for 24 hours under a nitrogen atmosphere. The solvent was then removed and replaced with 250 ml of dichloromethane. The mixture was washed with an equal volume of saturated aqueous sodium bicarbonate, with saturated aqueous sodium chloride, dried over sodium sulfate, filtered, and concentrated in vacuum. The residue was column chromatographed on 50 g of silica gel with a gradient elution commencing with chloroform and ending with 2% methanol in chloroform. The product-containing fractions were combined and concentrated in vacuum and the residue crystallized from isopropanol with the addition of 4N isopropanolic HCl to give 125 mg of title compound as a tan solid, monohydrochloride, quarter hydrate, m.p. 242°-244° C.
Reaction SMILES: [CH2:1]([O:7][C:8]1[CH:35]=[CH:34][C:11]([NH:12][C:13](=[S:33])[C:14]2[CH:19]=[CH:18][C:17]([CH2:20][O:21][CH:22]([C:29]([F:32])([F:31])[F:30])[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])=[CH:16][CH:15]=2)=[CH:10][CH:9]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[OH-].[Na+].O>CO.[Fe-3](C#N)(C#N)(C#N)(C#N)(C#N)C#N.[K+].[K+].[K+]>[F:31][C:29]([F:32])([F:30])[CH:22]([O:21][CH2:20][C:17]1[CH:18]=[CH:19][C:14]([C:13]2[S:33][C:10]3[CH:9]=[C:8]([O:7][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])[CH:35]=[CH:34][C:11]=3[N:12]=2)=[CH:15][CH:16]=1)[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28]
Reactant: CCCCCCOc1ccc(NC(=S)c2ccc(COC(CCCCCC)C(F)(F)F)cc2)cc1
Agent: N#C[Fe-3](C#N)(C#N)(C#N)(C#N)C#N
Agent: [K+]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: CCCCCCOc1ccc2nc(-c3ccc(COC(CCCCCC)C(F)(F)F)cc3)sc2c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 49 %

Procedure:
1.0 g (1.96 mM) of optically active 4'- hexyloxy-4-(1-trifluoromethylheptyloxymethyl)thiobenzanilide and 1.70 g (3.9 mM) of 90%-sodium hydroxide were dissolved in 15 ml of methanol. To the solution, 5 ml of an aqueous solution of 1.61 g (4.9 mM) of potassium ferricyanide was added dropwise, followed by stirring for 1 hour at room temperature. After the reaction, water was added to the reaction mixture, followed by filtration to obtain a crude crystal. The crude crystal was purified by silica gel column chromatography (eluent: toluene/hexane=1/2) and recrystallized two times from ethanol to obtain 0.49 g (0.97 mM) of optically active 2-[4-(1-trifluoromethylheptyloxymethyl)phenyl]-6-hexyloxybenzothiazole (Yield: 49%, m.p.=69.1° C.).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6](/[C:9](/[C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)=[CH:10]/[CH:11]=[CH:12]/[C:13]([OH:15])=[O:14])=[CH:5][CH:4]=1.[N+:22]([C:25]1[CH:30]=[CH:29][C:28](O)=[CH:27][CH:26]=1)([O-:24])=[O:23].C1(N=C=NC2CCCCC2)CCCCC1>ClCCl>[N+:22]([C:25]1[CH:30]=[CH:29][C:28]([O:14][C:13](=[O:15])/[CH:12]=[CH:11]/[CH:10]=[C:9](\[C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)/[C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)=[CH:27][CH:26]=1)([O-:24])=[O:23]
Reactant: COc1ccc(/C(=C/C=C/C(=O)O)c2cccnc2)cc1
Reactant: O=[N+]([O-])c1ccc(O)cc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: ClCCl
Product: COc1ccc(/C(=C\C=C\C(=O)Oc2ccc([N+](=O)[O-])cc2)c2cccnc2)cc1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
As in Example 115, (2E,4Z)-5-(4-methoxyphenyl)-5-(3-pyridinyl) -2,4-pentadienoic acid (5.7q) and 4-nitrophenol (306 g) in 80 mL of dichloromethane was treated with 1,3-dicyclohexylcarbodiimide (4.2 g) and the mixture was stirred at room temperature for 18 hours. After the usual work up, the ester was crystallized from 2-propanol to give 7.3 g of (E,E)-5-(4-methoxyphenyl)-5-(3-pyridinyl)-2,4-pentadienoic acid 4-nitrophenyl ester 129.5°-131° C. The analytical specimen was obtained from the same solvent, mp 130°-131° C.
Reaction SMILES: [OH:1][CH:2]1[CH:7]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][O:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[O:26][CH3:27])=[CH:10][CH:9]=2)[CH2:6][CH2:5][N:4]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:3]1.Br[CH2:36][C:37]1[CH:46]=[C:45]2[C:40]([CH:41]=[CH:42][N:43]=[CH:44]2)=[CH:39][CH:38]=1>>[CH:44]1[C:45]2[C:40](=[CH:39][CH:38]=[C:37]([CH2:36][O:1][CH:2]3[CH:7]([C:8]4[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][O:18][CH2:19][C:20]5[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=5[O:26][CH3:27])=[CH:10][CH:9]=4)[CH2:6][CH2:5][N:4]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:3]3)[CH:46]=2)[CH:41]=[CH:42][N:43]=1
Reactant: BrCc1ccc2ccncc2c1
Reactant: COc1ccccc1COCCCOc1ccc(C2CCN(C(=O)OC(C)(C)C)CC2O)cc1
Product: COc1ccccc1COCCCOc1ccc(C2CCN(C(=O)OC(C)(C)C)CC2OCc2ccc3ccncc3c2)cc1

Procedure:
In an analogous manner to that described in Example 1 (g), by alkylating tert-butyl (3RS,4RS)-3-hydroxy-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylate [Example 120 (g) (a)] with 7-bromomethyl-isoquinoline (WO 9,319,059) there was obtained tert-butyl (3RS,4RS)-3-(isoquinolin-7-ylmethoxy)-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylate as a light yellow resin; MS: 613 (M+H)+.
Reaction SMILES: [CH3:1][S:2][C:3]1[O:4][C:5]2[CH:11]=[C:10]([O:12][C:13]3[CH:18]=[CH:17][N:16]=[C:15]([C:19]([NH:21][CH3:22])=[O:20])[CH:14]=3)[CH:9]=[CH:8][C:6]=2[N:7]=1.ClC1C=C(C=CC=1)C(OO)=[O:28]>C(Cl)Cl>[CH3:1][S:2]([C:3]1[O:4][C:5]2[CH:11]=[C:10]([O:12][C:13]3[CH:18]=[CH:17][N:16]=[C:15]([C:19]([NH:21][CH3:22])=[O:20])[CH:14]=3)[CH:9]=[CH:8][C:6]=2[N:7]=1)=[O:28]
Reactant: CNC(=O)c1cc(Oc2ccc3nc(SC)oc3c2)ccn1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: CNC(=O)c1cc(Oc2ccc3nc(S(C)=O)oc3c2)ccn1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
To a solution of the 4-(2-(methylthio)benzo[d]oxazol-6-yloxy)-N-methylpyridine-2-carboxamide (1.26 g, 4.0 mmol, 1.0 eq) in 40 mL of methylene chloride was added 3-chloroperoxybenzoic acid (70%, 989 mg, 4.4 mmol, 1.1 eq). The reaction mixture was stirred at room temperature for 5 hours and then was diluted with 200 mL of methylene chloride. The resulting mixture was washed with aqueous sodium bicarbonate and brine then dried over MgSO4, filtered, and evaporated under reduced pressure to give crude product, which was used to next step without further purification. MH+=332.
Reaction SMILES: [NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[NH2:12])[CH:5]=[CH:4][CH:3]=1.[C:13](O)(=O)[CH:14]([CH3:16])[OH:15]>Cl>[CH3:13][CH:14]([C:16]1[NH:1][C:2]2[CH:3]=[CH:4][CH:5]=[C:6]3[C:11]=2[C:10]([N:12]=1)=[CH:9][CH:8]=[CH:7]3)[OH:15]
Reactant: CC(O)C(=O)O
Reactant: Nc1cccc2cccc(N)c12
Agent: Cl
Product: CC(O)C1=Nc2cccc3cccc(c23)N1
Reaction time: 2 h

Procedure:
A mixture of 32 g (0.2 mole) of 1,8-diaminonaphthalene and 32 g (0.3 mole) of 85% lactic acid in 400 ml of 4N hydrochloric acid is refluxed for 18 hr. The separated solid is filtered and converted to the free base by treatment with dilute ammonia for 2 hr. The new solid is filtered and recrystallized twice from 95% ethanol to give the product, α-methyl-2-perimidinemethanol, as yellow crystals, m.p. 205°-206° dec.
Reaction SMILES: C([S:4][C@@H:5]1[CH2:9][N:8]([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=2)=[O:11])[C@H:7]([CH:23]2[O:27][CH:26]([CH2:28]Br)[CH2:25][O:24]2)[CH2:6]1)(=O)C.[N-:30]=[N+:31]=[N-:32].[Na+].O.C(OCC)(=O)C>CN(C)C=O>[N:30]([CH2:28][CH:26]1[CH2:25][O:24][CH:23]([C@@H:7]2[CH2:6][C@H:5]([SH:4])[CH2:9][N:8]2[C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=2)=[O:11])[O:27]1)=[N+:31]=[N-:32]
Reactant: [N-]=[N+]=[N-]
Reactant: CC(=O)S[C@H]1C[C@@H](C2OCC(CBr)O2)N(C(=O)OCc2ccc([N+](=O)[O-])cc2)C1
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: [N-]=[N+]=NCC1COC([C@@H]2C[C@H](S)CN2C(=O)OCc2ccc([N+](=O)[O-])cc2)O1
Yield: 70.9 %

Procedure:
A solution of (2S,4S)-4-acetylthio-2-(4-bromomethyl-1,3-dioxolan-2-yl)-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (1.67 g) and sodium azide (0.24 g) in N,N-dimethylformamide (25 ml) was stirred at 60° C. for 1.5 hours, and the mixture was poured into a mixture of water (250 ml) and ethyl acetate (200 ml). The organic layer was separated, washed with brine, dried over magnesium sulfate and evaporated. The residue was dissolved in a mixture of methanol (8 ml) and tetrahydrofuran (8 ml), and then deacetylated by reacting the resultant product with 28% solution of sodium methoxide in methanol (0.7 ml) to give (2S,4S)-2-(4-azidomethyl-1,3-dioxolan-2-yl)-4-mercapto-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (0.99 g) in substantially the same manner as that of Preparation 7-(1).
Reaction SMILES: C(O[C:6]([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][O:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[CH2:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([O:30][CH3:31])[CH:25]=2)[CH2:9]1)=O)(C)(C)C.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[O:30]([C:26]1[CH:25]=[C:24]([CH2:23][CH2:22][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=2[O:15][CH2:14][C@H:10]2[O:11][CH2:12][CH2:13][N:8]([CH3:6])[CH2:9]2)[CH:29]=[CH:28][CH:27]=1)[CH3:31]
Reactant: COc1cccc(CCc2ccccc2OC[C@@H]2CN(C(=O)OC(C)(C)C)CCO2)c1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: COc1cccc(CCc2ccccc2OC[C@@H]2CN(C)CCO2)c1
Yield: 86.8 %

Procedure:
Following a procedure similar to that described in Example 38(a), 1.50 g of (S)-4-t-butoxycarbonyl-2-{2-[2-(3-methoxyphenyl)ethyl]phenoxymethyl}morpholine [prepared as described in Example 71(a)] were reacted with 167 mg of lithium aluminum hydride dispersed in 20 ml of tetrahydrofuran. The mixture was then worked up as described in Example 38(a), and the crude product thus obtained was purified by column chromatography through silica gel, using a 20:1 by volume mixture of methylene chloride and methanol as the eluent, to give 1.04 g (yield 87%) of the title compound as a colorless oil.
Reaction SMILES: [C:1]([NH:4][C:5]1[C:13]2[C:8](=[CH:9][C:10]([Cl:14])=[CH:11][CH:12]=2)[N:7](C(OCC)=O)[C:6]=1[C:20](=[O:28])[C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH3:27])[CH:22]=1)(=[O:3])[CH3:2].[CH2:29](O)C.C(OCC)C>>[C:1]([N:4]([C:5]1[C:13]2[C:8](=[CH:9][C:10]([Cl:14])=[CH:11][CH:12]=2)[NH:7][C:6]=1[C:20](=[O:28])[C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH3:27])[CH:22]=1)[CH3:29])(=[O:3])[CH3:2]
Reactant: CCOC(=O)n1c(C(=O)c2cccc(C)c2)c(NC(C)=O)c2ccc(Cl)cc21
Reactant: CCO
Solvent: CCOCC
Product: CC(=O)N(C)c1c(C(=O)c2cccc(C)c2)[nH]c2cc(Cl)ccc12

Procedure:
The title compound was prepared from 3-acetylamino-6-chloro-1-ethoxycarbonyl-2-(3-methylbenzoyl)indole (Example 22, step 1) according to the procedure described in Example 146. m.p.: 166-171° C. (ethanol/diethyl ether)
Reaction SMILES: [CH2:1]([O:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10])[CH:2]1[O:4][CH2:3]1.[OH-:11].[Na+]>C(O)(=O)CCCCC(O)=O.[OH-].[Na+].O>[CH2:1]([O:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10])[CH:2]([CH2:3][OH:11])[OH:4]
Reactant: [OH-]
Reactant: CCCCCOCC1CO1
Agent: O=C(O)CCCCC(=O)O
Agent: [Na+]
Solvent: O
Product: CCCCCOCC(O)CO
Temperature: 200 °C
Yield: 277.4 %

Procedure:
In an autoclave, 163 g of the crude pentyl glycidyl ether, 108 g of water, 7.3 g of adipic acid and 10.4 g of sodium hydroxide were charged. The resulting mixture was heated to 200° C. while stirring. After stirring for 2 hours, 1.6 g of sodium hydroxide was added. The resulting reaction mixture was dehydrated at 100° C. under reduced pressure (5.32 kPa), followed by purification by distillation under reduced pressure (133 to 266 Pa, 114 to 115° C.) , whereby 117 g of monopentyl glyceryl ether was obtained. As a result of GLC, it was found that the resulting compound had a purity not less than 99% and the content of organochlorine compounds was not greater than 100 ppm.
Reaction SMILES: [CH:1]1([OH:6])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:7]1[O:9][CH2:8]1.[Na]>>[CH:1]1([O:6][CH2:7][CH2:8][OH:9])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: OC1CCCC1
Reactant: C1CO1
Agent: [Na]
Product: OCCOC1CCCC1
Temperature: 75 °C

Procedure:
200 g (2.32 mols) of cyclopentanol, 38.5 cc (0.77 mol) of ethylene oxide and 2.3 g (0.1 g atom) of sodium metal are introduced at 0° C. into a 500 ml autoclave. The mixture is then heated for 4 hours at 75° C. The autoclave is left to cool and the reaction mixture is then distilled. This gives the title compound, which boils at 90°-92° C. under a pressure of 15 mm Hg.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]([C:12]1[CH:13]=[C:14]([NH2:18])[CH:15]=[CH:16][CH:17]=1)[CH2:6][C:5]2([CH3:20])[CH3:19].[CH2:21]([S:23](Cl)(=[O:25])=[O:24])[CH3:22]>N1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]([C:12]1[CH:13]=[C:14]([NH:18][S:23]([CH2:21][CH3:22])(=[O:25])=[O:24])[CH:15]=[CH:16][CH:17]=1)[CH2:6][C:5]2([CH3:20])[CH3:19]
Reactant: CCS(=O)(=O)Cl
Reactant: CC1(C)CC(c2cccc(N)c2)Nc2ccc(Cl)cc21
Solvent: c1ccncc1
Product: CCS(=O)(=O)Nc1cccc(C2CC(C)(C)c3cc(Cl)ccc3N2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 70.7 %

Procedure:
3-(6-Chloro-4,4-dimethyl-1,2,3,4-tetrahydro-quinolin-2-yl)-phenylamine (150 mg, 0.53 mmol) and ethanesulfonyl chloride (67 mg, 0.63 mmol) were dissolved in pyridine (5 mL). The mixture was stirred at room temperature overnight. The solvent was removed and the residue was purified on column chromatography using petroleum ether/ethyl acetate=5:1 as eluent to afford ethanesulfonic acid [3-(6-chloro-4,4-dimethyl-1,2,3,4-tetrahydro-quinolin-2-yl)-phenyl]-amide (142 mg, yield: 54%) as yellow solid. MS (ESI+APCI) M+1=445.1.
Reaction SMILES: N([O-])=O.[Na+].[N+:5]([C:8]1[CH:14]=[CH:13][C:11]([NH2:12])=[CH:10][CH:9]=1)([O-:7])=[O:6].[N-:15]=[N+:16]=[N-].[Na+]>O.FC(F)(F)C(O)=O>[N:12]([C:11]1[CH:13]=[CH:14][C:8]([N+:5]([O-:7])=[O:6])=[CH:9][CH:10]=1)=[N+:15]=[N-:16]
Reactant: [N-]=[N+]=[N-]
Reactant: Nc1ccc([N+](=O)[O-])cc1
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: [N-]=[N+]=Nc1ccc([N+](=O)[O-])cc1
Reaction time: 0.17 h
Yield: 99.3 %

Procedure:
A solution of sodium nitrite (761 mg, 11 mmol) in water (5 mL) was added dropwise to a 0° C. solution of 4-nitroaniline (508 mg, 3.68 mmol) in trifluoroacetic acid (5 mL). After stirring for 10 minutes, a solution of sodium azide (1.55 g, 23.9 mmol) was added slowly. The resulting yellow suspension was stirred at room temperature for 5 hours. The reaction mixture was partitioned between water and ethyl acetate. The organic layer was dried over sodium sulfate, filtered and concentrated. Purification by column chromatography gave 1-azido-4-nitrobenzene (600 mg, 99%). 1H NMR (400 MHz, CDCl3, δ): 8.16-8.19 (m, 2H), 7.05-7.09 (m, 2H).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[CH:7]2)([O-:3])=[O:2].Br[CH2:14][C:15]1[CH:22]=[CH:21][C:18]([C:19]#[N:20])=[CH:17][C:16]=1[O:23][CH3:24]>O1CCOCC1.[Ag-]=O.[Ag]=O>[C:19]([C:18]1[CH:21]=[CH:22][C:15]([CH2:14][C:7]2[C:6]3[C:10](=[CH:11][CH:12]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)[NH:9][CH:8]=2)=[C:16]([O:23][CH3:24])[CH:17]=1)#[N:20]
Reactant: O=[N+]([O-])c1ccc2[nH]ccc2c1
Reactant: COc1cc(C#N)ccc1CBr
Agent: O=[Ag-]
Agent: O=[Ag]
Solvent: C1COCCO1
Product: COc1cc(C#N)ccc1Cc1c[nH]c2ccc([N+](=O)[O-])cc12
Temperature: 100 °C
Reaction time: 1 h
Yield: 30.5 %

Procedure:
An efficiently stirred mixture of 5-nitroindole (3.24 g.), bromide (W) (4.57 g.) and silver (I) oxide (4.87 g.) in dry dioxane (90 ml.) was heated at 100° C. for 5 hours. Additional silver oxide (2 g.) was added, and heating continued for 1 hour. The cooled mixture was evaporated, the residue diluted with dichloromethane, filtered, washing the filter cake with dichloromethane until the washings were colorless, and the combined filtrate evaporated. The product was purified by flash chromatography on silica gel, eluting with 3:7 v/v ethyl acetate:hexane, giving a product which was crystallized from a mixture of ethyl acetate and hexane to give 3-(4-cyano-2-methoxybenzyl)-5-nitroindole (1.87 g., 30%) as a yellow powder, m.p. 204°-206° C.; partial NMR (80 MHz, DMSO-d6): 3.92(s,3H, OMe); 4.12(s,2H, ArCH2).
Reaction SMILES: [CH2:1]([C@:3]12[CH2:11][CH2:10][C@@H:9]3[C:12]4[CH:13]=[CH:14][C:15]([O:20]C)=[CH:16][C:17]=4[CH2:18][CH2:19][C@H:8]3[C@@H:7]1[CH2:6][CH2:5][C@@H:4]2[OH:22])[CH3:2].N.[Li]>O.O1CCCC1.C(O)C>[CH2:1]([C@:3]12[CH2:11][CH2:10][C@@H:9]3[C@@H:12]4[C:17]([CH2:18][CH2:19][C@H:8]3[C@@H:7]1[CH2:6][CH2:5][C@@H:4]2[OH:22])=[CH:16][C:15](=[O:20])[CH2:14][CH2:13]4)[CH3:2]
Reactant: CC[C@]12CC[C@@H]3c4ccc(OC)cc4CC[C@H]3[C@@H]1CC[C@@H]2O
Agent: N
Agent: [Li]
Solvent: CCO
Solvent: C1CCOC1
Solvent: O
Product: CC[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@@H]43)[C@@H]1CC[C@@H]2O

Procedure:
Add 13β-ethyl-3-methoxy-gona-1,3,5(10)-trien-17β-ol (0.5 g.) in 100 ml. of tetrahydrofuran to 150 ml. of liquid ammonia, followed by 0.5 g. of lithium foil, and stir the mixture for 10 minutes. Add ethanol (6 ml.) and tetrahydrofuran (10 ml.) over a period of 20 minutes. After disappearance of the blue color add water, extract the mixture well with ether and evaporate the washed and dried ether extract. Dissolve the crystalline residue in 50 ml. of methanol and reflux for 30 minutes with 30 ml. of 3N HCL. Remove most of the methanol under reduced pressure, and extract the residue with ether. Chromatograph the ether extract on alumina. Use benzene-ether (1:1) to elute 13-β-ethyl-17β-hydroxy-gon-4-en-3-one; m.p. 152°-55° C.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[NH:9][C:10]([CH2:12]Cl)=[O:11].[CH3:14][C:15]1[NH:19][CH2:18][CH2:17][N:16]=1>[N+](C)([O-])=O>[CH3:14][C:15]1[N:19]([CH2:12][C:10](=[O:11])[NH:9][C:3]2[C:2]([CH3:1])=[CH:7][CH:6]=[CH:5][C:4]=2[CH3:8])[CH2:18][CH2:17][N:16]=1
Reactant: CC1=NCCN1
Reactant: Cc1cccc(C)c1NC(=O)CCl
Solvent: C[N+](=O)[O-]
Product: CC1=NCCN1CC(=O)Nc1c(C)cccc1C
Temperature: 25 °C
Reaction time: 17 h

Procedure:
To a solution of 10.0 gm. (0.05 M) of 2-chloro-2',6'-acetoxylidide in 100 ml. of nitromethane add 21.35 gm (0.254 M) of lysidine. Stir the solution at room temperature for about 17 hours. Follow the progress of the reaction by thin layer chromatography on silica gel (acetonitrile:ammonium hydroxide:methanol, 85:10:5). At the completion of the reaction, remove the solvent in vacuo, to the residue add 150 ml. of water, adjust the pH to about 7.0 with conc. hydrochloric acid. Extract the resultant solution with 3×100 ml. methylene chloride and discard. Adjust the pH of the water layer to about 11-11.5 with 50% sodium hydroxide. Extract with 4×200 ml. of methylene chloride. Take the combined latter extracts and wash 3×50 ml. of water. Dry the methylene chloride extracts over Na2SO4. Evaporate the solvents to provide the title compound.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([O:9]COC)[C:6]([O:13][CH3:14])=[C:5]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]/[CH:20]=[CH:21]\[CH2:22][CH2:23][CH2:24][CH3:25])[C:4]=1[O:26]COC.Cl.C1C=CC=CC=1.C(=O)([O-])O.[Na+]>C(O)(C)C.O1CCCC1.CO.C(OCC)(=O)C.C1C=CC=CC=1>[CH3:14][O:13][C:6]1[C:7](=[O:9])[CH:8]=[C:3]([O:2][CH3:1])[C:4](=[O:26])[C:5]=1[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]/[CH:20]=[CH:21]\[CH2:22][CH2:23][CH2:24][CH3:25]
Reactant: CCCC/C=C\CCCCCc1c(OC)c(OCOC)cc(OC)c1OCOC
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CC(C)O
Solvent: c1ccccc1
Product: CCCC/C=C\CCCCCC1=C(OC)C(=O)C=C(OC)C1=O
Reaction time: 3 h

Procedure:
500 Milligrams of 1,4-dimethoxy-2,5-bis(methoxymethoxy)-3-(Z-6-undecenyl)benzene was dissolved in 10 ml of a mixed solvent of isopropanol-tetrahydrofuran, and at room temperature, under nitrogen gas stream conditions, 2 ml of isopropanol-tetrahydrofuran (1:1) solution containing 20% of hydrogen chloride was added thereto and the whole mixture was stirred for 3 hours. The solvent was removed by evaporating under reduced pressure on a water bath at below 20° C. The residue obtained was further treated by evaporation under reduced pressure with adding 20 ml of benzene so as to remove hydrogen chloride. The residue obtained was dissolved in 20 ml of methanol, and a small amount of sodium hydrogen carbonate was added, and the mixture was stirred for 1 hour under oxygen gas stream conditions. The color of the reaction mixture turned yellow, and the solvent was removed by evaporation under reduced pressure. The residue obtained was treated by means of a separative silica gel thin layer chromatography (F254, thickness: 2 mm, developer: 10% ethyl acetate-benzene) to obtain 320 mg of 2,5-dimethoxy-3(Z-6-undecenyl)-1,4-benzoquinone. Yellow oily substance.
Reaction SMILES: [Si]([O:8][C@@H:9]1[CH2:13][CH:12]([CH:14]2[CH2:16][CH2:15]2)[N:11]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C@H:10]1[CH:24]1[CH2:26][CH2:25]1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C1COCC1>[CH:24]1([C@H:10]2[C:9](=[O:8])[CH2:13][CH:12]([CH:14]3[CH2:16][CH2:15]3)[N:11]2[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:25][CH2:26]1
Reactant: CC(C)(C)OC(=O)N1C(C2CC2)C[C@@H](O[Si](C)(C)C(C)(C)C)[C@@H]1C1CC1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1C(C2CC2)CC(=O)[C@@H]1C1CC1
Reaction time: 2 h
Yield: 44.7 %

Procedure:
(2S,3R)-tert-Butyl 3-(tert-butyldimethylsilyloxy)-2,5-dicyclopropylpyrrolidine-1-carboxylate (19) (412 mg, 1.08 mmol) was dissolved in THF (1 mL) and placed under nitrogen. TBAF (IM THF, 1.29 mL) was added and the reaction stirred for 2 hr. The reaction was concentrated in vacuo and used without further purification. This material was dissolved in CH2Cl2 (2 mL) and placed under nitrogen. Dess-Martin reagent (788 mg, 1.86 mmol) was added and the reaction quenched with sat. aq. NaHCO3 (2 mL) followed by sat. Na2S2O3 (2 mL) when complete as indicated by TLC monitoring. The organic layer was isolated and concentrated in vacuo. The resulting crude product was purified by column chromatography using EtOAc/hexane gradients to yield (2S)-tert-butyl 2,5-dicyclopropyl-3-oxopyrrolidine-1-carboxylate (20) (128 mg, 45% over two steps) as a yellow oil.