Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[CH:5][CH:4]=1)#[N:2].[ClH:12].[NH:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1.C(N(CC)CC)C>C(O)C.C(OCC)(=O)C>[ClH:12].[NH:2]=[C:1]([N:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1)[C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[CH:5][CH:4]=1
Reactant: C1CCNC1
Reactant: N#Cc1ccc(C(=O)O)cc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Solvent: CCO
Product: N=C(c1ccc(C(=O)O)cc1)N1CCCC1
Reaction time: 120 h

Procedure:
15.2 g (103 mmol) of 4-cyano-benzoic acid was added to 200 ml of an ethyl acetate solution containing 4 N hydrogen chloride and 50 ml of ethanol, and they were stirred for 5 days. The solvent was distilled off under reduced pressure, and 100 ml of ethyl acetate was added to the resulting solid, and the mixture was stirred for 30 minutes, and the solid was collected by filtration. The resulting solid was reacted with 15.0 g (211 mmol) of pyrrolidine and 10.0 g (98.8 mmol) of triethylamine for 2 days in 100 ml ethanol as the solvent. The solvent was distilled off, and 40 ml of 6 N hydrochloric acid was added to the residue, and it was reacted at 85° C. for 4 hours. The solvent was distilled off, and 50 ml of 1 N hydrochloric acid was added to the residue which was then stilled for 30 minutes, and the solid was collected by filtration and washed with 20 ml of ice-cold water. It was dried under reduced pressure to obtain the title compound.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([OH:17])=[C:6]([C:8](=[O:16])[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:7]=1.[C:18](OC(=O)C)(=O)[CH3:19].C([O-])(=O)C.[Na+]>>[F:1][C:2]1[CH:7]=[C:6]2[C:5](=[CH:4][CH:3]=1)[O:17][C:18]([CH3:19])=[C:9]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:8]2=[O:16]
Reactant: CC(=O)OC(C)=O
Reactant: O=C(Cc1ccccc1)c1cc(F)ccc1O
Agent: CC(=O)[O-]
Agent: [Na+]
Product: Cc1oc2ccc(F)cc2c(=O)c1-c1ccccc1
Temperature: 25 °C
Yield: 80 %

Procedure:
Intermediate 50 (50 g, 0.217 moles) was taken in a RB flask and to this acetic anhydride (424 ml) and sodium acetate (124 g, 1.51 moles) were added and the mixture was refluxed for 12 h. After cooling to RT, the reaction mixture was quenched by the addition of ice cold water. The solid formed was filtered and washed with water. The product was dried under vacuum to afford the title compound as colourless solid (44 g, 80% yield). 1H-NMR (δ ppm, CDCl3, 400 MHz): δ 7.87 (dd, J=8.3, 3.0 Hz, 1H), 7.47-7.35 (m, 5H), 7.29 (m, 2H), 2.32 (s, 3H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.C(N(CC)CC)C.[CH3:18][S:19](Cl)(=[O:21])=[O:20]>O1CCCC1>[CH3:18][S:19]([NH:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2)(=[O:21])=[O:20]
Reactant: CS(=O)(=O)Cl
Reactant: Nc1ccc2[nH]ccc2c1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CS(=O)(=O)Nc1ccc2[nH]ccc2c1
Yield: 94.5 %

Procedure:
To a solution of 2.0 gm (15.1 mMol) 5-amino-1H-indole in 25 mL tetrahydrofuran were added 2.4 mL (17.2 mMol) triethylamine. The reaction mixture was cooled in an ice bath as 1.23 mL (15.9 mMol) methanesulfonyl chloride were added dropwise. After 3.5 hours the reaction mixture was partitioned between 1N sodium hydroxide and ethyl acetate. The organic phase was extracted twice with 1N sodium hydroxide. All sodium hydroxide phases were combined, adjusted to pH=5 with acid and extracted well with ethyl acetate. These organic phases were combined, washed sequentially with water and saturated aqueous sodium chloride, dried over sodium sulfate and concentrated under reduced pressure to give 3.0 gm of a purple solid. This solid was crystallized from cyclohexane/ethyl acetate to give 2.5 gm (78.6%) of the title compound as light purple crystals.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][C:13]([C:15]2[CH:20]=[CH:19][C:18]([O:21]CC=C)=[CH:17][CH:16]=2)=[O:14])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].C1(C)C=CC(S(O)(=O)=O)=CC=1>CO.O.[Pd]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][C:13]([C:15]2[CH:16]=[CH:17][C:18]([OH:21])=[CH:19][CH:20]=2)=[O:14])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
Reactant: C=CCOc1ccc(C(=O)C=Cc2ccc(OC)c(OC)c2)cc1
Agent: [Pd]
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: CO
Product: COc1ccc(C=CC(=O)c2ccc(O)cc2)cc1OC
Temperature: 80 °C
Yield: 29.3 %

Procedure:
486 mg (1.5 mmol) of 3,4-dimethoxy-4′-allyloxychalcone was dissolved in a mixture of 7.5 ml of methanol and 1.5 ml of water. To the solution were added 150 mg of p-tolu-enesulfonic acid and 150 mg of palladium on carbon (10%) and the solution was heated to 80° C. for 2 h in a sealed flask. The reaction mixture was filtered and poured into a mixture of 10 ml of an aqueous 10% solution of sodium bicarbonate and 10 ml of a saturated aqueous solution of sodium chloride. The mixture was extracted with 15 ml of ethyl acetate and concentrated in vacuo. The residue was recrystallized from methanol to give 0.125 g (25%) of 3,4-dimethoxy-4′-hydroxychalcone (m.p. 193-198° C.) identical to that described by A.v.n Wacek, and E. David, Ber. 70 (1937), 190 (m.p. 208° C.
Reaction SMILES: [C:1]1([N:7]2[C:11]([NH:12][C:13]([NH2:15])=[S:14])=[CH:10][C:9]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:22][I:23]>>[IH:23].[C:1]1([N:7]2[C:11]([NH:12][C:13](=[NH:15])[S:14][CH3:22])=[CH:10][C:9]([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)=[N:8]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CI
Reactant: NC(=S)Nc1cc(-c2ccccc2)nn1-c1ccccc1
Product: CSC(=N)Nc1cc(-c2ccccc2)nn1-c1ccccc1
Product: I

Procedure:
(1,3-Diphenyl-5-pyrazolyl) thiourea (119.7 g.) and 63.9 g. methyl iodide were reacted as described in Example V to give 156.1 g. of product, mp 178°-182° C.
Reaction SMILES: [CH3:1][C:2]1([CH3:16])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[CH:11][C:12]([NH2:15])=[N:13][CH:14]=2)[O:3]1.[C:17](Cl)(=[O:22])[C:18]([CH3:21])([CH3:20])[CH3:19].C(N(CC)CC)C>N1C=CC=CC=1.C(OCC)(=O)C>[CH3:8][C:6]1([CH3:7])[C:2]([CH3:16])([CH3:1])[O:3][B:4]([C:9]2[CH:10]=[CH:11][C:12]([NH:15][C:17](=[O:22])[C:18]([CH3:21])([CH3:20])[CH3:19])=[N:13][CH:14]=2)[O:5]1
Reactant: CC(C)(C)C(=O)Cl
Reactant: CC1(C)OB(c2ccc(N)nc2)OC1(C)C
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Solvent: CCN(CC)CC
Product: CC(C)(C)C(=O)Nc1ccc(B2OC(C)(C)C(C)(C)O2)cn1
Temperature: 0 °C
Yield: 57.5 %

Procedure:
5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (0.5 g, 2.27 mmol), pivaloyl chloride (0.277 g, 2.20 mmol) and triethylamine (0.248 g, 2.45 mmol) in pyridine (10 mL) were stirred at room temperature overnight. The mixture was diluted with ethyl acetate and ice/water and the layers were separated. The aqueous phase was extracted with ethyl acetate and the combined extracts dried over sodium sulfate. Purification by chromatography (1:1 ethyl acetate in hexanes) gave the product (0.385 g, 56% yield) as a white solid. 1H-NMR (300 MHz, CDCl3) δ 8.60 (s, 1H), 8.23 (d, 1H), 8.06 (d, 2H), 1.33 (s, 12H), 1.31 (s, 9H). MS (ES+) m/z 305 (M+1).
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][C:5]([C:7]1[CH:12]=[CH:11][C:10](F)=[CH:9][CH:8]=1)=O.[CH3:14][C:15]1[NH:16][CH:17]=[CH:18][N:19]=1>>[CH3:14][C:15]1[N:19]2[CH2:2][CH2:3][CH:4]=[C:5]([C:7]3[CH:12]=[CH:11][C:10]([N:16]4[CH:17]=[CH:18][N:19]=[C:15]4[CH3:14])=[CH:9][CH:8]=3)[C:18]2=[CH:17][N:16]=1
Reactant: O=C(CCCCl)c1ccc(F)cc1
Reactant: Cc1ncc[nH]1
Product: Cc1nccn1-c1ccc(C2=CCCn3c2cnc3C)cc1
Temperature: 200 °C

Procedure:
50 g (0.25 mol) of 4-chloro-4'-fluorobutyrophenone are combined with 130 g (1.58 mol) of 2-methylimidazole and heated to 200° C. under nitrogen for 18 hr. Crystallization from ethyl acetate provides the title compound.
Reaction SMILES: [F:1][C:2]([F:11])([F:10])[C:3]1[CH:4]=[C:5]([CH:7]=[CH:8][CH:9]=1)[NH2:6].C(N(CC)CC)C.Cl[C:20](=[O:27])[CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23]>CC(C)=O>[O:27]=[C:20]([NH:6][C:5]1[CH:7]=[CH:8][CH:9]=[C:3]([C:2]([F:10])([F:11])[F:1])[CH:4]=1)[CH2:21][C:22]([O:24][CH2:25][CH3:26])=[O:23]
Reactant: CCOC(=O)CC(=O)Cl
Reactant: Nc1cccc(C(F)(F)F)c1
Solvent: CCN(CC)CC
Solvent: CC(C)=O
Product: CCOC(=O)CC(=O)Nc1cccc(C(F)(F)F)c1
Temperature: 0 °C
Reaction time: 8 h
Yield: 99 %

Procedure:
To an ice-cooled solution of 3-(trifluoromethyl)aniline (64.5 g, 0.40 mol) and triethylamine (60 ml) in acetone (700 ml) was added dropwise, ethyl 3-chloro-3-oxopropanoate (63.6 g, 0.42 mol) in acetone (50 ml). After the addition (approx. 30 minutes) stirring was continued at room temperature overnight. The solvents were removed and water (1200 ml) was added. The resulting precipitate was filtered off, thoroughly washed twice with water and then dried to afford the title compound as yellow powder (109 g, 99%).
Reaction SMILES: [Cl:1][C:2]1[N:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:3]=1[C:4](O)=[O:5].C(Cl)(=O)C(Cl)=O.C[N:19](C=O)C.[NH4+].[OH-]>C(Cl)Cl>[Cl:1][C:2]1[N:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:3]=1[C:4]([NH2:19])=[O:5]
Reactant: O=C(O)c1ccc(Cl)nc1Cl
Reactant: CN(C)C=O
Agent: O=C(Cl)C(=O)Cl
Agent: [NH4+]
Agent: [OH-]
Solvent: ClCCl
Product: NC(=O)c1ccc(Cl)nc1Cl
Temperature: 25 °C

Procedure:
A suspension of 2,6-dichloronicotinic acid (5 g, 26.0 mmol) in CH2Cl2 (20 mL) was treated with oxalyl dichloride (3.97 g, 31.3 mmol) and few drops of DMF, and stirred at rt. The generation of bubbles was observed and the reaction mixture gradually became clear. The resulting clear solution was concentrated on a rotary evaporator to remove traces of oxalyl chloride, dissolved in CH2Cl2 (20 mL), treated with aqueous NH4OH (3.47 mL, 52.1 mmol) added drop-wise, and stirred at rt for 1 h. The resulting mixture was diluted with CH2Cl2 (white precipitate doesn't all dissolve), washed with satd. NaHCO3, and concentrated to obtain 2.97 g of 2,6-dichloronicotinamide as a white solid. LCMS: (M+H)+=190.96 (100%) 192.93 (70%) 194.93 (20%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:17][CH2:16][C:11]3(OCC[O:12]3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Cl.C(O)C.S(=O)(=O)(O)O>O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:9][CH2:10][C:11](=[O:12])[CH2:16][CH2:17]2)=[CH:6][CH:7]=1
Reactant: Fc1ccc(C2CCC3(CC2)OCCO3)cc1
Agent: Cl
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CCO
Product: O=C1CCC(c2ccc(F)cc2)CC1

Procedure:
A mixture of 160 parts of 8-(4-fluorophenyl)-1,4-dioxaspiro[4,5]decane, 72 parts of hydrochloric acid, 800 parts of ethanol and 800 parts of water is stirred and refluxed for 2 h. 30. Then there are added dropwise 72 parts of sulfuric acid. Upon completion, stirring is continued at reflux temperature for one hour. The reaction mixture is cooled, poured onto water and the product is extracted with trichloromethane. The extract is washed with water, dried, filtered and evaporated. The residue is fractionated, yielding 68.5 parts of 4-(4-fluorophenyl)cyclohexanone; b.p. 110° C. at 1 mm. pressure.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][C:3]=1[CH3:11].[Cl:12][C:13]1[CH:14]=[C:15]([CH2:19][N:20]2[CH:24]=[CH:23][N:22]=[C:21]2[CH3:25])[N:16]=[N:17][CH:18]=1>>[ClH:12].[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:13]2[CH:14]=[C:15]([CH2:19][N:20]3[CH:24]=[CH:23][N:22]=[C:21]3[CH3:25])[N:16]=[N:17][CH:18]=2)=[CH:4][C:3]=1[CH3:11]
Reactant: Cc1cc(B(O)O)ccc1F
Reactant: Cc1nccn1Cc1cc(Cl)cnn1
Product: Cc1cc(-c2cnnc(Cn3ccnc3C)c2)ccc1F
Product: Cl

Procedure:
The title compound, MS: m/e=283.1 (M+H+), was prepared from 4-fluoro-3-methylphenylboronic acid (commercially available) and 5-chloro-3-(2-methyl-imidazol-1-yl-methyl)-pyridazine.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[O:12])[O:10][C:8](=O)[C:7]2=[CH:13][CH:14]=1)([O-:3])=[O:2].[NH2:15][CH2:16][C:17]([OH:19])=[O:18].O.C(O)C>CN(C)C=O>[N+:1]([C:4]1[CH:5]=[C:6]2[C:11](=[O:12])[N:15]([CH2:16][C:17]([OH:19])=[O:18])[C:8](=[O:10])[C:7]2=[CH:13][CH:14]=1)([O-:3])=[O:2]
Reactant: O=C1OC(=O)c2cc([N+](=O)[O-])ccc21
Reactant: NCC(=O)O
Solvent: CCO
Solvent: CN(C)C=O
Solvent: O
Product: O=C(O)CN1C(=O)c2ccc([N+](=O)[O-])cc2C1=O
Yield: 77.5 %

Procedure:
A solution of 4-nitrophthalic anhydride (9.66 g, 50 mmol) and glycine (3.75 g, 50 mmol) in N,N-dimethylformamide was stirred for 30 minutes at 140° C. The reaction mixture was poured into water (150 mL). Resulting precipitate was collected by filtration and washed with water, which was collected by filtration and washed with water, which was recrystallized from ethanol to give 9.69 g (yield 77%) of the titled compound, m.p. 195.5°-196.5° C. (ethanol).
Reaction SMILES: [C:1]1([CH3:16])[CH:6]=[C:5]([CH3:7])[CH:4]=[C:3]([CH3:8])[C:2]=1[C:9]1[C:14]([NH2:15])=[CH:13][CH:12]=[CH:11][N:10]=1.[C:17]([CH:20]1[CH2:25][CH2:24][O:23][C:21]1=[O:22])(=O)[CH3:18]>C1(C)C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[C:1]1([CH3:16])[CH:6]=[C:5]([CH3:7])[CH:4]=[C:3]([CH3:8])[C:2]=1[C:9]1[C:14]([NH:15][C:17](=[C:20]2[CH2:25][CH2:24][O:23][C:21]2=[O:22])[CH3:18])=[CH:13][CH:12]=[CH:11][N:10]=1
Reactant: CC(=O)C1CCOC1=O
Reactant: Cc1cc(C)c(-c2ncccc2N)c(C)c1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: Cc1ccccc1
Product: CC(Nc1cccnc1-c1c(C)cc(C)cc1C)=C1CCOC1=O
Yield: 64.4 %

Procedure:
p-Toluenesulfonic acid monohydrate (39 mg, 0.20 mmol) was added to a solution of 2-mesityl-3-pyridinamine (3.9 g, 18 mmol) and α-acetyl-γ-butyrolactone (4.7 g, 37 mmol) in toluene (80 mL). The mixture was heated under reflux for seven days while removing water using Dean-Stark apparatus. The mixture was evaporated, and the resulting crystals were washed with 60% diethyl ether/ethyl acetate, to give the title compound (3.74 g) as white crystals.
Reaction SMILES: Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]([OH:14])=[O:13])=[CH:4][CH:3]=1.[Cu]C#N.[OH-:18].[Na+].Cl.CN(C)[CH:23]=[O:24]>>[C:2]1([C:23]([OH:24])=[O:18])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]([OH:14])=[O:13])=[CH:4][CH:3]=1
Reactant: [OH-]
Reactant: O=C(O)c1ccc(Br)c2ccccc12
Reactant: CN(C)C=O
Agent: N#C[Cu]
Agent: Cl
Agent: [Na+]
Product: O=C(O)c1ccc(C(=O)O)c2ccccc12

Procedure:
125.6 parts by weight of 4-bromo-1-naphthoic acid with a melting point of 219°-220° and 51 parts by weight of copper-(I) cyanide (67-71% copper) are introduced into 330 parts by weight of dimethylformamide. The mixture is then heated under reflux for 4 hours, whilst stirring, to 150°-160° C., whereby, after some time, the solid materials go into solution, but then the 4-cyano-1-naphthoic acid copper bromide complex is gradually precipitated. After cooling to about 100°, the reaction mixture is diluted with 330 parts by weight of water and stirred for approximately one hour at room temperature, and the precipitate is filtered off by suction and rinsed with about 400 parts by weight of water. The 4-cyanonaphthoic acid/copper bromide complex thus isolated is introduced into 550 parts by weight of 20% sodium hydroxide solution and heated under reflux for 5 hours. The mixture is then adjusted to pH 7.0-7.5 with about 220 parts by weight of concentrated hydrochloric acid, the solution is filtered off by suction from the copper oxide slurry deposited and this slurry is rinsed with about 500 parts by weight of water, in portions. The naphthalene-1,4-dicarboxylic acid is precipitated from the filtrate at pH 2 by the addition of about 100 parts by weight of concentrated hydrochloric acid, and the precipitate is filtered off under suction and is washed with water until free of chloride ions. After drying, 92 parts by weight of a practically colorless naphthalene-1,4-dicarboxylic acid with a melting point of 315°-320° are obtained.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N+:20]([O-])=O)[CH:5]=[C:6]2[C:11]=1[N:10]([CH2:12][CH2:13][CH:14]1[CH2:18][CH2:17][CH2:16][N:15]1[CH3:19])[CH2:9][CH2:8][CH2:7]2.[H][H]>O1CCCC1.C(O)C.[Pd]>[F:1][C:2]1[CH:3]=[C:4]([NH2:20])[CH:5]=[C:6]2[C:11]=1[N:10]([CH2:12][CH2:13][CH:14]1[CH2:18][CH2:17][CH2:16][N:15]1[CH3:19])[CH2:9][CH2:8][CH2:7]2
Reactant: [H][H]
Reactant: CN1CCCC1CCN1CCCc2cc([N+](=O)[O-])cc(F)c21
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CCO
Product: CN1CCCC1CCN1CCCc2cc(N)cc(F)c21
Reaction time: 4 h
Yield: 99.1 %

Procedure:
To a stirred solution of 8-fluoro-1-(2-(1-methylpyrrolidin-2-yl)ethyl)-6-nitro-1,2,3,4-tetrahydroquinoline (660 mg, 2.147 mmol) in tetrahydrofuran (6 ml) and ethanol (6.00 ml) was added palladium on carbon, 10 wt % (229 mg, 0.215 mmol). The suspension was stirred under balloon pressure of hydrogen and monitored by TLC. After 4 h, the reaction was complete. The mixture was then filtered through a pad of celite which was washed with methanol. The filtrate was then concentrated and dried on a high vacuum pump. The residue (8-fluoro-1-(2-(1-methylpyrrolidin-2-yl)ethyl)-1,2,3,4-tetrahydroquinolin-6-amine (590 mg, 2.127 mmol, 99% yield)) was used directly in the subsequent reaction. 1H NMR (DMSO-d6) δ 6.16 (dd, J=14.7, 2.4 Hz, 1H); 6.04 (m, 1H), 4.70 (brs, 1H), 2.99-2.93 (m, 3H), 2.88-2.82 (m, 2H), 2.57-2.53 (m, 2H), 2.24 (s, 3H), 2.15-2.05 (m, 2H); 1.93-1.87 (m, 2H), 1.69-1.60 (m, 4H), 1.44-1.35 (m, 2H).
Reaction SMILES: C(O[CH:4](OCC)[CH2:5][O:6][C@H:7]([CH2:17][CH:18]=[CH2:19])[CH2:8][O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)C.Cl.[NH2:24][OH:25]>C(O)(=O)C.O.COC(C)(C)C>[CH2:10]([O:9][CH2:8][C@H:7]([O:6][CH2:5][CH:4]=[N:24][OH:25])[CH2:17][CH:18]=[CH2:19])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: C=CC[C@H](COCc1ccccc1)OCC(OCC)OCC
Reactant: NO
Agent: Cl
Solvent: CC(=O)O
Solvent: O
Solvent: COC(C)(C)C
Product: C=CC[C@H](COCc1ccccc1)OCC=NO
Reaction time: 1 h

Procedure:
({[(2R)-2-(2,2-Diethoxyethoxy)pent-4-en-1-yl]oxy}methyl)benzene (C2) (12.4 g, 40.2 mmol) was dissolved in acetic acid (28 mL) and water (12 mL). Hydroxylamine hydrochloride (2.84 g, 40.9 mmol) was added as a solid. After 1 hour, additional hydroxylamine hydrochloride (2.84 g, 40.9 mmol) was added. After 1 more hour, the reaction mixture was diluted with tert-butyl methyl ether (100 mL) and washed with water (3×50 mL), then washed with aqueous potassium carbonate solution (0.5 M, 100 mL). The organic layer was concentrated to provide the product as a pale yellow oil, which consisted of a roughly equimolar mixture of oxime isomers, as assessed by 1H NMR. Yield: 9.60 g, 38.5 mmol, 96%. 1H NMR (400 MHz, CDCl3) δ 7.98 and 7.67 (2 br s, total 1H), [7.50 (t, J=5.6 Hz) and 6.95 (t, J=3.6 Hz), total 1H], 7.28-7.39 (m, 5H), 5.74-5.87 (m, 1H), 5.04-5.14 (m, 2H), 4.55 and 4.56 (2 s, total 2H), 4.47-4.49 (m, 1H), 4.18-4.28 (m, 1H), 3.47-3.65 (m, 3H), 2.30-2.37 (m, 2H).
Reaction SMILES: [Cl:1][C:2]1[N:7]([CH3:8])[C:6](=[O:9])[N:5]([CH3:10])[C:4](=[O:11])[CH:3]=1.[N+:12]([O-])([OH:14])=[O:13]>>[Cl:1][C:2]1[N:7]([CH3:8])[C:6](=[O:9])[N:5]([CH3:10])[C:4](=[O:11])[C:3]=1[N+:12]([O-:14])=[O:13]
Reactant: O=[N+]([O-])O
Reactant: Cn1c(Cl)cc(=O)n(C)c1=O
Product: Cn1c(Cl)c([N+](=O)[O-])c(=O)n(C)c1=O

Procedure:
To 25 ml of surfuric acid was gradually added 8.5 g (0.049 mol) of 6-chloro-1,3-dimethyluracil as described in Synthesis Example 1. To the solution was gradually added at 0° to 5° C. 8.5 ml of fuming nitric acid and the mixture was stirred for 5 minutes. The reaction solution was poured onto ice and extracted twice with chloroform. The organic layer was dried with anhydrous magnesium sulfate, concentrated and the crystals thus-obtained were recrystallized from a solvent mixture of ethyl acetate and hexane to obtain 7.5 g of 6-chloro-1,3-dimethyl-5-nitrouracil.
Reaction SMILES: [CH3:1][C:2]1([CH3:20])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=2)[NH:5][CH:4]([C:13]2[CH:14]=[C:15]([NH2:19])[CH:16]=[CH:17][CH:18]=2)[CH2:3]1.N1C=CC=CC=1.[F:27][C:28]1[CH:29]=[C:30]([S:34](Cl)(=[O:36])=[O:35])[CH:31]=[CH:32][CH:33]=1>ClCCl>[F:27][C:28]1[CH:29]=[C:30]([S:34]([NH:19][C:15]2[CH:16]=[CH:17][CH:18]=[C:13]([CH:4]3[CH2:3][C:2]([CH3:20])([CH3:1])[C:11]4[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=4)[NH:5]3)[CH:14]=2)(=[O:36])=[O:35])[CH:31]=[CH:32][CH:33]=1
Reactant: O=S(=O)(Cl)c1cccc(F)c1
Reactant: Cc1ccc2c(c1)C(C)(C)CC(c1cccc(N)c1)N2
Solvent: ClCCl
Solvent: c1ccncc1
Product: Cc1ccc2c(c1)C(C)(C)CC(c1cccc(NS(=O)(=O)c3cccc(F)c3)c1)N2
Yield: 37.7 %

Procedure:
To a stirred mixture of 3-(4,4,6-trimethyl-1,2,3,4-tetrahydro-quinolin-2-yl)-phenylamine (135 mg, 0.5 mmol) in dichloromethane (3 mL) was added pyridine (60 mg, 0.75 mmol) in dichloromethane (2 mL) and 3-fluoro-benzenesulfonyl chloride (108 mg, 0.56 mmol) under nitrogen. The resultant mixture was stirred for 4 h. The reaction mixture was diluted with dichloromethane, washed with water (twice), saturated brine, and dried over magnesium sulfate. Magnesium sulfate was removed by filtration, and after evaporation, the residue was purified on chromatography column (silica gel, petroleum ether: Ethyl acetate=12:1) to afford 80 mg of 3-fluoro-N-[3-(4,4,6-trimethyl-1,2,3,4-tetrahydro-quinolin-2-yl)-phenyl]-benzenesulfonamide as yellow solid (Yield: 38%). MS (ESI+APCI) M+1=425.2.
Reaction SMILES: [CH2:1]1[CH2:5][O:4][CH:3](N2C(=O)NC(=O)C(F)=C2)[CH2:2]1.[CH2:15]=[CH:16][CH3:17].[CH3:18]O>[Ti]>[CH3:18][CH:5]([OH:4])[C:1]1[CH:2]=[CH:3][CH:17]=[CH:16][CH:15]=1
Reactant: C=CC
Reactant: CO
Reactant: O=c1[nH]c(=O)n(C2CCCO2)cc1F
Agent: [Ti]
Product: CC(O)c1ccccc1
Temperature: 37 °C

Procedure:
A 300 ml glass-lined autoclave equipped with a Teflon stir shaft and blade and thermowell was charged with methanol (25 ml) and "TS-1" titanium silicalite catalyst (0.73g), followed by liquid propylene (16 mL; 0.20 mole). The autoclave was heated to 37° C. by means of an external coil attached to a circulating bath. A crude oxidant mixture (100 mL) obtained by air oxidation of alpha-methyl benzyl alcohol and containing 5.15 weight percent hydrogen peroxide was charged to an Isco pump and added to the contents of the autoclave over a 1 hour period. The reaction mixture exothermed to 45° C. and was stirred at this temperature for an additional 2 hours after addition was completed. The pressure dropped from 120 psia to ca. 42 psia during the reaction. The external heating cord was replaced with an ice bath and the liquid contents of the autoclave cooled to 20° C. The autoclave was vented and the head removed for product sampling. The reaction product was analyzed by iodometric titration (residual hydrogen peroxide) and gas chromatography (organic products). The results are shown in Table I below (Example 6). Epoxide selectivity with respect to olefin was over 99%, with no detectable amount of propylene glycol and less than 1% of 2-methoxy-1-propanol and 1-methoxy-2-propanol being produced.
Reaction SMILES: Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][CH3:12])=[C:4]([NH2:13])[N:3]=1.[OH-].[Na+].[CH2:16]([OH:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>>[CH2:16]([O:23][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH2:11][CH3:12])=[C:4]([NH2:13])[N:3]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: OCc1ccccc1
Reactant: CCn1cnc2c(N)nc(Cl)nc21
Agent: [Na+]
Agent: [OH-]
Product: CCn1cnc2c(N)nc(OCc3ccccc3)nc21
Temperature: 85 °C

Procedure:
To a mixture of 2-chloro-9-ethyl-9H-purin-6-ylamine (0.2 g, 1.01 mmol), a compound of formula (3), and dry sodium hydroxide (5 mmol) was added benzyl alcohol (9.0 mmol). This mixture was heated at 85° C. for 3 hours. The solvent was then removed under reduced pressure and the residue was neutralized with 2N HCl and extracted with CHCl3. The organic layer was dried (Na2SO4) and concentrated in vacuo. The residue was chromatographed on a silica gel column eluting with a mixture of ethyl acetate/cyclohexane/methanol (60/33/5) to give 2-benzyloxy-9-ethyl-9H-purin-6-ylamine as a chromatographically pure solid.