Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [ClH:1].[Cl:2][CH2:3][CH2:4][CH2:5][N:6]([CH2:10][CH2:11][CH3:12])[CH2:7][CH2:8][CH3:9].[NH2:13][C:14]([NH2:16])=[S:15].C(OCC)(=O)C>C(O)C>[ClH:2].[ClH:1].[CH2:7]([N:6]([CH2:10][CH2:11][CH3:12])[CH2:5][CH2:4][CH2:3][S:15][C:14](=[NH:13])[NH2:16])[CH2:8][CH3:9]
Reactant: NC(N)=S
Reactant: CCCN(CCC)CCCCl
Agent: Cl
Solvent: CCO
Solvent: CCOC(C)=O
Product: CCCN(CCC)CCCSC(=N)N
Temperature: 25 °C
Reaction time: 24 h
Yield: 89.6 %

Procedure:
A stirred mixture of 1-chloro-3-(dipropylamino)-propane hydrochloride (42 g), thiourea (15.5 g) and ethanol (250 ml) was heated under reflux for 24 hours then allowed to cool to ambient temperature. Ethyl acetate was added until a faint opalescence was observed, then the mixture was stored at 4° C. for 24 hours. After this time it had deposited an oil which was isolated by decantation of the bulk of the solvent followed by removal of residual solvent in vacuo. The oil was triturated with ethanol, the solvent was removed by decantation, and the residue was dried in vacuo at ambient temperature for 24 hours to give a pale brown solid. The ethanol solution decanted from the oil was concentrated in vacuo, and the residue was triturated with ethanol as described above to give a second crop of pale brown solid. The ethanol solution remaining after isolation of the second crop was concentrated in vacuo and the residue was triturated with propan-2-ol to give a third crop of solid. The three crops were combined to give S-[3-(dipropylamino)propyl]isothiourea dihydrochloride as a pale brown solid (51 g), m.p 143°-145° C.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][O:16][CH2:17][C:18]([CH3:20])=[CH2:19])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ClC1C=CC=C(C(OO)=[O:29])C=1>>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:15][O:16][CH2:17][C:18]2([CH3:20])[CH2:19][O:29]2)=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C=C(C)COCc1ccc(OCc2ccccc2)cc1
Reactant: O=C(OO)c1cccc(Cl)c1
Product: CC1(COCc2ccc(OCc3ccccc3)cc2)CO1
Yield: 95 %

Procedure:
Epoxidation of alkene 122 with 3-chloroperbenzoic acid as in Example 2G for 2.5 h, followed by chromatography of the product on silica gel, eluting with 50% CH2Cl2/petroleum ether (foreruns) and then with 50-80% CH2Cl2/petroleum ether and CH2Cl2, gave 2-({[4-(benzyloxy)benzyl]oxy}methyl)-2-methyloxirane (124) (95%) as an oil: 1H NMR (CDCl3) δ 7.45-7.29 (m, 5H), 7.26 (dt, J=8.7, 2.4 Hz, 2H), 6.95 (dt, J=8.7, 2.5 Hz, 2H), 5.07 (s, 2H), 4.52 (d, J=11.6 Hz, 1H), 4.47 (d, J=11.6 Hz, 1H), 3.54 (d, J=11.0 Hz, 1H), 3.42 (d, J=11.0 Hz, 1H), 2.73 (d, J=4.9 Hz, 1H), 2.62 (d, J=4.9 Hz, 1H), 1.39 (s, 3H); HREIMS calcd for C18H20O3 m/z (M+) 284.1412. found 284.1416.
Reaction SMILES: [Cl:1][C:2]1[C:7]([C:8]([O:10]CC)=[O:9])=[CH:6][N:5]=[C:4](Cl)[CH:3]=1.S(=O)(=O)(O)[OH:15]>>[Cl:1][C:2]1[C:7]([C:8]([OH:10])=[O:9])=[CH:6][N:5]=[C:4]([OH:15])[CH:3]=1
Reactant: O=S(=O)(O)O
Reactant: CCOC(=O)c1cnc(Cl)cc1Cl
Product: O=C(O)c1cnc(O)cc1Cl

Procedure:
ethyl 4,6-dichloronicotinate (17 g) is boiled for 4 hours with 24% sulfuric acid (400 ml). The white crystals that separate are filtered from the boiling solution and 4-chloro-6-hydroxynicotinic acid (6 g, m.p. 299°-300° C.) is obtained; the acidic solution is left overnight in the refrigerator. The crystallized solid is collected by filtration and dried under vacuum, thus obtaining 6-chloro-4-hydroxynicotinic acid (4.6 g) m.p. 231°-233° C.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[CH:6][C:7]([NH:24][CH2:25][CH3:26])=[C:8]([N:10]=[C:11]2[N:15]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C:14](=[O:23])[CH2:13][S:12]2)[CH:9]=1)(=[O:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:37](Br)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>C1COCC1>[C:1]([C:4]1[CH:5]=[CH:6][C:7]([NH:24][CH2:25][CH3:26])=[C:8]([N:10]=[C:11]2[N:15]([CH2:16][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:14](=[O:23])[CH:13]([CH2:37][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[S:12]2)[CH:9]=1)(=[O:3])[CH3:2]
Reactant: CCNc1ccc(C(C)=O)cc1N=C1SCC(=O)N1Cc1ccccc1
Reactant: BrCc1ccccc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: CCNc1ccc(C(C)=O)cc1N=C1SC(Cc2ccccc2)C(=O)N1Cc1ccccc1
Temperature: 0 °C
Reaction time: 2 h
Yield: 8 %

Procedure:
To a stirred solution of 2-(5-acetyl-2-ethylamino-phenylimino)-3-benzyl-thiazolidin-4-one (0.11 g, 0.30 mmol) in THF (3 mL, anhyd) chilled to 0° C. was added dropwise 1.0 M solution of lithium bis(trimethylsilyl)amide in THF (0.30 mL, 0.30 mmol). After 5 min benzyl bromide (36 μL, 0.30 mmol) was added to the reaction mixture, which was stirred at 0° C. for 2 h and then allowed to warm to ambient temperature. After 1 h the reaction mixture was quenched with satd NH4Cl and extracted with EtOAc. The organic layer was isolated, washed with brine, dried over anhyd Na2SO4, concentrated and chromatographed (silica gel, 0:100 to 20:80 EtOAc-Hex) to yield the title product (11 mg) as a white solid. 1H-NMR (CDCl3): δ 7.66 (1H, dd, J=8.5 Hz, 2.0 Hz), 7.49 (1H, d, J=2.0 Hz), 7.19-7.35 (10H, m), 6.48 (1H, d, J=8.5 Hz), 5.00 (2H, m), 4.48 (1H, dd, J=9.0 Hz, 3.8 Hz), 3.92 (1H, hr t), 3.53 (1H, dd, J=14.1 Hz, 3.8 Hz), 3.17 (1H, dd, J=14.1 Hz, 9.0 Hz), 3.02 (2H, m), 2.47 (3H, s), 1.02 (3H, t); MS (ESI): 458 (MH+).
Reaction SMILES: [OH2:1].C.[Se](=O)=O.C([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH:15][S:16]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)(=[O:18])=[O:17])(=O)C.[O:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1>>[CH2:26]([O:25][CH:30]([OH:1])[C:29]([C:12]1[CH:11]=[C:10]([NH:15][S:16]([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)(=[O:17])=[O:18])[CH:9]=[CH:14][CH:13]=1)=[O:28])[CH3:27]
Reactant: CC(=O)c1ccccc1NS(=O)(=O)c1ccccc1
Reactant: O
Reactant: C1COCCO1
Agent: O=[Se]=O
Product: CCOC(O)C(=O)c1cccc(NS(=O)(=O)c2ccccc2)c1
Temperature: 80 °C
Reaction time: 96 h
Yield: 46 %

Procedure:
1 ml of water, 1 g activated charcoal and 2.66 g (24 mmol) selenium dioxide was added to a solution of 1.65 g (6.00 mmol) N-(acetylphenyl)benzenesulphonamide in about 10 mL dioxane. The reaction mixture was stirred for approx. 4 d at 80° C. and then the solvent was eliminated using the rotary evaporator. The residue was dissolved in about 30 ml of ethanol and refluxed for approx. 4 h. The solvent was eliminated from the reaction mixture using the rotary evaporator, the residue was dissolved in about 100 mL ethyl acetate, washed about three times with 30 ml saturated aqueous sodium hydrogen carbonate solution, dried over sodium sulphate and the solvent was eliminated using the rotary evaporator. 0.917 g (2.73 mmol, 46%) N-[3-(2-ethoxy-2-hydroxyacetyl)-phenyl]-benzenesulphonamide were obtained as a yellow solid.
Reaction SMILES: [CH3:1][Si:2]([CH3:16])([CH3:15])[CH2:3][CH2:4][O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)=[O:7].C([O-])=O.[NH4+:20]>[Pd].O.CO>[CH3:1][Si:2]([CH3:16])([CH3:15])[CH2:3][CH2:4][O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH2:20])[CH2:10][CH2:9]1)=[O:7]
Reactant: [NH4+]
Reactant: C[Si](C)(C)CCOC(=O)N1CCC(=O)CC1
Agent: [Pd]
Agent: O=C[O-]
Solvent: O
Solvent: CO
Product: C[Si](C)(C)CCOC(=O)N1CCC(N)CC1
Reaction time: 8 h
Yield: 40.1 %

Procedure:
A slurry of 10% palladium on carbon (200 mg) in water was added to 4-oxo-piperidine-1-carboxylic acid-2-trimethylsilanyl-ethyl ester (2.42 g, 10 mmol) in 100 mL of methanol. Ammonium formate (6.0 g, 95 mmol) in water was added dropwise, and the mixture stirred vigorously overnight. The mixture was filtered and the filtrate concentrated in vacuo to leave the crude product. Chromatography (elution with methanol-dichloromethane) provided 0.98 g of product.
Reaction SMILES: O[CH2:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[C:8]([CH2:13][CH:14]([CH3:16])[CH3:15])[C:7]([CH2:17][NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[C:6]2[C:26]1[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.[CH3:45][CH2:46][O:47][C:48]([CH2:50][SH:51])=[O:49].[H-].[Na+]>CN(C)C=O.O1CCCC1>[C:21]([O:20][C:19]([NH:18][CH2:17][C:7]1[C:8]([CH2:13][CH:14]([CH3:16])[CH3:15])=[N:9][C:10]2[C:5]([C:6]=1[C:26]1[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=1)=[CH:4][C:3]([CH2:2][S:51][CH2:50][C:48]([O:47][CH2:46][CH3:45])=[O:49])=[CH:12][CH:11]=2)=[O:25])([CH3:24])([CH3:23])[CH3:22]
Reactant: Cc1ccc(-c2c(CNC(=O)OC(C)(C)C)c(CC(C)C)nc3ccc(CO)cc23)cc1
Reactant: CCOC(=O)CS
Agent: CS(=O)(=O)Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCOC(=O)CSCc1ccc2nc(CC(C)C)c(CNC(=O)OC(C)(C)C)c(-c3ccc(C)cc3)c2c1
Reaction time: 0.5 h
Yield: 82 %

Procedure:
To a mixture of tert-butyl [6-(hydroxymethyl)-2-isobutyl-4-(4-methylphenyl)quinolin-3-yl]methylcarbamate (1.1 g, 2.5 mmol), triethylamine (0.53 ml, 3.8 mmol) and tetrahydrofuran (50 ml) was added methanesulfonyl chloride (0.3 ml, 3.8 mmol) under ice-cooling, and the mixture was stirred for 30 min. A mixture of ethyl thioglycollate (0.42 ml, 3.8 mmol), sodium hydride (60% in oil, 0.15 g, 3.8 mmol) and N,N-dimethylformamide (3 ml) were added to the reaction mixture and the mixture was stirred at room temperature for 15 min. The reaction mixture was partitioned between ethyl acetate and water and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give ethyl ({[3-{[(tert-butoxycarbonyl)amino]methyl}-2-isobutyl-4-(4-methylphenyl)quinolin-6-yl]methyl}thio)acetate (1.1 g, yield 83%) as a white powder.
Reaction SMILES: Cl[C:2]1[C:7]([CH:8]=O)=[C:6]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([CH3:20])([CH3:19])[C:17]#[N:18])[N:11]=2)[CH:5]=[CH:4][N:3]=1.[NH2:21][NH2:22]>O1CCCC1.C(O)C.O.NN>[NH:21]1[C:2]2=[N:3][CH:4]=[CH:5][C:6]([C:10]3[N:11]=[C:12]([C:16]([CH3:20])([CH3:19])[C:17]#[N:18])[CH:13]=[CH:14][CH:15]=3)=[C:7]2[CH:8]=[N:22]1
Reactant: NN
Reactant: CC(C)(C#N)c1cccc(-c2ccnc(Cl)c2C=O)n1
Solvent: O
Solvent: C1CCOC1
Solvent: CCO
Product: CC(C)(C#N)c1cccc(-c2ccnc3[nH]ncc23)n1
Temperature: 140 °C
Yield: 22 %

Procedure:
A mixture of 2-(2′-chloro-3′-formyl-2,4′-bipyridin-6-yl)-2-methylpropanenitrile (71 mg, 0.25 mmol) and 1M solution of hydrazine in tetrahydrofuran (3 ml) was heated under microwave irradiation at 140° C. for 20 minutes. The mixture was cooled down to room temperature, diluted with ethanol (1 ml) and hydrazine hydrate (1 ml) was added. The reaction mixture was heated under microwave irradiation at 160° C. for 30 minutes. The mixture was cooled down to room temperature, partitioned between ethyl acetate and water. The organic phase was dried over magnesium sulfate, filtered and evaporated to dryness. The residue was purified on silica gel by flash column chromatography to afford the title compound as a white solid (14.6 mg, 22% yield).
Reaction SMILES: C(OC(O[CH2:8][CH3:9])CBr)C.Cl.[C:11]1([C:17]2[CH:22]=[CH:21][N:20]=[C:19]([NH2:23])[CH:18]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C([O-])(O)=O.[Na+]>O.O1CCOCC1.CO>[C:11]1([C:17]2[CH:22]=[CH:21][N:20]3[CH:8]=[CH:9][N:23]=[C:19]3[CH:18]=2)[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: CCOC(CBr)OCC
Reactant: Nc1cc(-c2ccccc2)ccn1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: O
Solvent: C1COCCO1
Product: c1ccc(-c2ccn3ccnc3c2)cc1
Temperature: 23 °C
Reaction time: 2 h

Procedure:
A mixture of bromoacetaldehyde diethyl acetal (0.88 mL, 5.9 mmol, 2.0 equiv) and concentrated HCl (0.1 mL, 0.4 equiv) in water (15 mL) was stirred at 23° C. for 2 h, then heated at 80° C. for 30 min. The mixture was allowed to cool to 23° C., and 4-phenylpyridin-2-amine (1-3, 0.50 g, 2.9 mmol, 1 equiv) and NaHCO3 (0.59 g, 7.1 mmol, 2.4 equiv) were added. The resulting mixture was then heated to 50° C. where MeOH (2 mL) and dioxane (3 mL) were added to increase solubility. The reaction mixture was stirred at 50° C. for 18 h, then concentrated. The residue was partitioned between EtOAc (200 mL) and brine (200 mL). The organic layer was concentrated to provide 7-phenylimidazo[1,2-a]pyridine (1-4) as a brown solid. 1H NMR (300 MHz, CDCl3) δ 8.18 (d, 1H, J=7.3 Hz), 7.84 (s, 1H), 7.67 (s, 1H), 7.66 (s, 2H, J=7.3 Hz), 7.60 (s, 1H), 7.49 (t, 2H, J=7.5 Hz), 7.40 (t, 1H, J=7.3 Hz), 7.09 (dd, 1H, J=7.0, 1.2 Hz).
Reaction SMILES: Cl.[NH2:2][C@@H:3]([CH2:15][O:16][C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]#[N:24])[CH:18]=1)[CH2:4][C:5]([O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:6].C(N(CC)CC)C.[C:32]1([C:38]2[CH:46]=[CH:45][C:41]([C:42](Cl)=[O:43])=[CH:40][CH:39]=2)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>CN(C)C=O.O>[C:38]1([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH:39]=[CH:40][C:41]([C:42]([NH:2][C@@H:3]([CH2:15][O:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([C:23]#[N:24])[CH:18]=2)[CH2:4][C:5]([O:7][CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[O:6])=[O:43])=[CH:45][CH:46]=1
Reactant: O=C(Cl)c1ccc(-c2ccccc2)cc1
Reactant: N#Cc1cccc(OC[C@H](N)CC(=O)OCc2ccccc2)c1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: O
Solvent: CN(C)C=O
Product: N#Cc1cccc(OC[C@@H](CC(=O)OCc2ccccc2)NC(=O)c2ccc(-c3ccccc3)cc2)c1
Reaction time: 0.5 h

Procedure:
310 mg (1.0 mmol) of benzyl (3R)-3-amino-4-(3-cyanophenoxy)butyrate hydrochloride was dissolved in 10 ml of dimethylformamide. 0.18 ml (1.3 mmol) of triethylamine was added to the solution. 282 mg (1.3 mmol) of 4-phenylbenzoyl chloride was added to the resultant mixture under cooling with ice, and they were stirred for 30 minutes. The temperature was elevated to room temperature, and the reaction mixture was stirred for additional 2 hours. The reaction liquid was diluted with water. After the extraction with ethyl acetate, the organic layer was successively washed with water, 1 N hydrochloric acid, saturated aqueous sodium hydrogencarbonate solution and saturated aqueous NaCl solution, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by the silica gel column chromatography to obtain the title compound.
Reaction SMILES: [CH2:1]([C:3]([CH:12]([C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=1)[CH2:13][C:14]1[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=1[N+:21]([O-])=O)([C:8]([O:10][CH3:11])=[O:9])[C:4]([O:6][CH3:7])=[O:5])[CH3:2].Cl.C(OCC)(=O)C.C(=O)([O-])[O-].[K+].[K+]>CO>[CH2:1]([C:3]([CH:12]([C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=1)[CH2:13][C:14]1[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=1[NH2:21])([C:8]([O:10][CH3:11])=[O:9])[C:4]([O:6][CH3:7])=[O:5])[CH3:2]
Reactant: CCC(C(=O)OC)(C(=O)OC)C(Cc1cc(Cl)ccc1[N+](=O)[O-])c1ccc(OC)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CO
Product: CCC(C(=O)OC)(C(=O)OC)C(Cc1cc(Cl)ccc1N)c1ccc(OC)cc1
Reaction time: 2 h

Procedure:
α -Ethyl-[2-(5-chloro-2-nitrophenyl)-1-(4-methoxyphenyl) ethyl]propanedioic acid, dimethyl ester (12.64 g, 28.10 mmole) was dissolved in methanol (600 ml) under argon at room temperature. Powdered stannous chloride dihydrate (32.98 g, 146.2 mmole, 5.2 eq) was added followed by concentrated hydrochloric acid (36 ml) with stirring. The solution turned clear and homogeneous. After 2 hours, Celite, ethyl acetate and saturated potassium carbonate solution were added with stirring. (The potassium carbonate solution was added portionwise). The suspension was filtered though a pad of Celite and the Celite pad was rinsed with ethyl acetate (3 times). The filtrate was concentrated to remove most of the organic solvents, and the residue was collected by suction-filtration. The crude material was used without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[O:11][CH3:12])/[C:7](=[C:13](\[C:19]#[N:20])/C(OCC)=O)/[CH2:6][CH2:5]2.[C-:21]#[N:22].[K+]>C(O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[O:11][CH3:12])[C:7]([CH2:13][C:19]#[N:20])([C:21]#[N:22])[CH2:6][CH2:5]2
Reactant: CCOC(=O)/C(C#N)=C1\CCc2cc(Cl)c(OC)cc21
Reactant: [C-]#N
Agent: [K+]
Solvent: CCO
Solvent: O
Product: COc1cc2c(cc1Cl)CCC2(C#N)CC#N
Temperature: 67.5 °C
Reaction time: 24 h
Yield: 13.3 %

Procedure:
To a solution of (E)-ethyl 2-(5-chloro-6-methoxy-2,3-dihydro-1H-inden-1-ylidene)-2-cyanoacetate (Prep16, 6.02 g, 24.4 mmol) in ethanol (25 ml) was added a solution of KCN (3.61 g, 60 mmol) in water. The mixture was stirred for one day at 65-70° C. Water was added and extracted with ethyl acetate twice. The organic phases were combined and dried over anhydrous Na2SO4, concentrated and purified by FC to afford the title compound (800 mg, y=16%).
Reaction SMILES: [CH2:1]([OH:10])[CH2:2][O:3][CH2:4][CH2:5][O:6][CH2:7][CH2:8][OH:9].[N+:11]([C:14]1[CH:22]=[CH:21][C:17]([C:18](Cl)=[O:19])=[CH:16][CH:15]=1)([O-:13])=[O:12].[C:23](=[O:26])(O)[O-].[Na+]>>[N+:11]([C:14]1[CH:22]=[CH:21][C:17]([C:18]([C:1]([OH:10])([C:23](=[O:26])[C:17]2[CH:21]=[CH:22][C:14]([N+:11]([O-:13])=[O:12])=[CH:15][CH:16]=2)[CH2:2][O:3][CH2:4][CH2:5][O:6][CH2:7][CH2:8][OH:9])=[O:19])=[CH:16][CH:15]=1)([O-:13])=[O:12]
Reactant: OCCOCCOCCO
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])cc1
Reactant: O=C([O-])O
Agent: [Na+]
Product: O=C(c1ccc([N+](=O)[O-])cc1)C(O)(COCCOCCO)C(=O)c1ccc([N+](=O)[O-])cc1

Procedure:
Triethylene glycol (45 g, 0.3 mole) was treated with excess p-nitrobenzoyl chloride (116 g, 0.62 mole), following the general procedure outlined in Example 1, Part A. After treating with aqueous sodium bicarbonate to remove excess acid chloride, the product was recrystallized from ethyl acetate to give bis-(4-nitrobenzoyl)-triethylene glycol (115 g) as a pale yellow solid, m.p. 104°-105° C. The product was homogeneous by TLC.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([OH:18])=[O:17])[CH:11]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2].C(Cl)(=O)C(Cl)=O.[C:25](O)([CH3:28])([CH3:27])[CH3:26].[Li]CCCC>C(Cl)Cl.CN(C=O)C.C1COCC1>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([C:16]([O:18][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:17])[CH:11]=2)=[CH:8][CH:9]=1)([O-:3])=[O:2]
Reactant: O=C(O)c1cccc(-c2ccc([N+](=O)[O-])cc2)c1
Reactant: CC(C)(C)O
Agent: O=C(Cl)C(=O)Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC(C)(C)OC(=O)c1cccc(-c2ccc([N+](=O)[O-])cc2)c1
Yield: 57 %

Procedure:
To a solution of 15 (1.215 g, 5 mmol) in 30 mL of methylene chloride was added oxalyl chloride (0.65 mL, 7.45 mmol) and one drop of DMF. The mixture was stirred until no further bubbling was observed. The clear solution was exaporated to dryness to give the crude acid chloride. To another flask containing 7.0 mL of tert-butanol was added n-BuLi (1.8 M in hexane, 2.8 mL, 5.04 mmol) under a water bath. The turbid solution was stirred for 5 min at room temperature and then the above acid chloride in 20 mL of THF was added through a dropping funnel. The mixture was stirred overnight before the solvents were evaporated. The residue was dissolved into methylene chloride and washed with 0.5 N NaOH. The organic layer was dried over MgSO4 and evaporated. The residue was recrystallized from methanol to give pale yellow crystals (851 mg, 57%). m.p. 110.5-111.0° C. 1H NMR (CDCl3) δ 8.32 (d, 7.8 Hz, 2H), 8.24 (s, 1H), 8.06 (d, 7.7 Hz, 1H), 7.77 (m, 3H), 7.56 (t, 7.7 Hz, 1H), 1.63 (s, 9H). 13C NMR (CDCl3) δ 165.1, 147.1, 146.5, 138.7, 132.8, 131.0, 129.6, 129.0, 128.2, 127.8, 124.0, 81.4, 28.0, LRMS (EI) for C17H17O4N 299 (M+, 20), 243 (70), 266 (30), 152 (25; HRMS (EI) calcd 299.1157, obsd 299.1192. Anal. (C17H17NO4) C, H, N.
Reaction SMILES: B1(C)[O:8][C:7]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17]C=2)([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C@@H]2N1CCC2.B.C1COCC1.C1(=O)C2=C3C(=CC=C2)C=CC=C3C1.Cl>ClCCl.CO>[C@@H:7]1([OH:8])[C:9]2=[C:10]3[C:11](=[CH:12][CH:13]=[CH:14]2)[CH:17]=[CH:18][CH:19]=[C:20]3[CH2:15]1
Reactant: CB1OC(c2ccccc2)(c2ccccc2)[C@H]2CCCN12
Agent: B
Agent: Cl
Agent: O=C1Cc2cccc3cccc1c23
Solvent: CO
Solvent: ClCCl
Solvent: C1CCOC1
Product: O[C@H]1Cc2cccc3cccc1c23
Temperature: -30 °C
Reaction time: 0.75 h
Yield: 20.6 %

Procedure:
(R)-2-Methyl-CBS-oxazaboro-lidine (50 ml, 1 mol toluene solution) was cooled to −30° C., and a borane-THF complex (250 ml, 1 mol THF solution) was added. The mixture was stirred for 45 min. Acenaphthen-1-one (40 g, 240 mmol) was dissolved in dichloromethane (500 ml) and the solution was added dropwise. The mixture was stirred under cooling (−30° C.) for 2 hr. Then, methanol (80 ml) and 1N-hydrochloric acid (100 ml) were added under ice-cooling, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated aqueous ammonium chloride solution, dried over magnesium sulfate, and concentrated to give (S)-1-acenaphthenol (35 g) as pale-yellow crystals.
Reaction SMILES: [S:1]1[C:5]([C:6]2([OH:19])[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[C:12]3[C:7]2=[CH:8][CH:9]=[CH:10][CH:11]=3)=[CH:4][C:3]2C=CC=[CH:23][C:2]1=2.S1C=CC2C=CC=CC1=2.C1C2C(=O)C3C(=CC=CC=3)C=2C=CC=1>>[CH3:23][C:2]1[S:1][C:5]([C:6]2([OH:19])[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[C:12]3[C:7]2=[CH:8][CH:9]=[CH:10][CH:11]=3)=[CH:4][CH:3]=1
Reactant: OC1(c2cc3ccccc3s2)c2ccccc2-c2ccccc21
Agent: O=C1c2ccccc2-c2ccccc21
Agent: c1ccc2sccc2c1
Product: Cc1ccc(C2(O)c3ccccc3-c3ccccc32)s1

Procedure:
9-(Benzo[b]thien-2-yl)-9H-fluoren-9-ol: from benzo[b]thiophene (thianaphthene) and 9-fluorenone;
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][CH:3]=[N:2]1.Cl[C:7]1[C:15]2[C:14]([NH:16][CH2:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22]4[O:25][CH2:26][O:27][C:21]=4[CH:20]=3)=[N:13][CH:12]=[N:11][C:10]=2[S:9][C:8]=1[CH3:28]>>[N:1]1([C:12]2[N:13]=[C:14]([NH:16][CH2:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22]4[O:25][CH2:26][O:27][C:21]=4[CH:20]=3)[C:15]3[CH:7]=[C:8]([CH3:28])[S:9][C:10]=3[N:11]=2)[CH:5]=[CH:4][CH:3]=[N:2]1
Reactant: Cc1sc2ncnc(NCCc3ccc4c(c3)OCO4)c2c1Cl
Reactant: c1cn[nH]c1
Product: Cc1cc2c(NCCc3ccc4c(c3)OCO4)nc(-n3cccn3)nc2s1

Procedure:
Following the procedure of Example 97, the reaction of pyrazole with 5-chloro-6-methyl-4-(3,4-methylenedioxyphenethylamino)-thieno-[2,3-d]-pyrimidine gives 2-(pyrazol-1-yl)-6-methyl-4-(3,4-methylenedioxyphenethylamino)-thieno-[2,3-d]-pyrimidine.
Reaction SMILES: [C:1]([O:5][C:6](=[O:28])[CH2:7][C@H:8]([C:18]1[O:22][N:21]=[C:20]([C:23](OCC)=[O:24])[N:19]=1)[CH2:9][CH2:10][CH2:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(O)C>[CH:12]1([CH2:11][CH2:10][CH2:9][C@@H:8]([C:18]2[O:22][N:21]=[C:20]([CH2:23][OH:24])[N:19]=2)[CH2:7][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:28])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]1
Reactant: CCOC(=O)c1noc([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)n1
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: CC(C)(C)OC(=O)C[C@@H](CCCC1CCCCC1)c1nc(CO)no1
Temperature: 25 °C
Reaction time: 5 h
Yield: 98.7 %

Procedure:
A solution of ethyl 5-{(1R)-1-[2-(tert-butoxy)-2-oxoethyl]-4-cyclohexylbutyl}-1,2,4-oxadiazol-3-carboxylate (Preparation 3) (15.2 g, 38.50 mmol) in ethanol (120 ml) was treated with portions of sodium borohydride (1.46 g, 38.50 mmol) and the resulting mixture was was stirred at room temperature under a nitrogen atmosphere for 5 hours. Aqueous citric acid (5% w/v solution) was added slowly and the mixture was stirred at room temperature for a further 30 minutes. The organic solvent was removed under reduced pressure. The aqueous layer was diluted with water and extracted with ethyl acetate giving an emulsion. Anhydrous sodium chloride was added to break up the emulsion. The combined organic layers were washed with saturated sodium hydrogen carbonate solution and brine, dried over anhydrous sodium sulphate, filtered and the solvent removed under reduced pressure to afford the title compound as a colourless oil (13.4 g).