Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:17]([C:18](=O)[CH2:19][CH2:20][CH3:21])=[CH:16][CH:15]=[C:14]2[C:10]=1[CH:11]=[CH:12][N:13]2[CH3:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:24]([NH2:28])([CH3:27])([CH3:26])[CH3:25]>ClCCCl.C(Cl)Cl.Cl[Ti](Cl)(Cl)Cl>[CH2:1]([O:8][C:9]1[C:17]([C:18](=[N:28][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:19][CH2:20][CH3:21])=[CH:16][CH:15]=[C:14]2[C:10]=1[CH:11]=[CH:12][N:13]2[CH3:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCCC(=O)c1ccc2c(ccn2C)c1OCc1ccccc1
Reactant: CC(C)(C)N
Agent: Cl[Ti](Cl)(Cl)Cl
Solvent: ClCCCl
Solvent: ClCCl
Product: CCCC(=NC(C)(C)C)c1ccc2c(ccn2C)c1OCc1ccccc1
Temperature: 25 °C

Procedure:
To a solution of 1-(4-(benzyloxy)-1-methyl-1H-indol-5-yl)butan-1-one (0.260 g, 0.85 mmol) in DCE (4 mL) was added t-BuNH2 (0.40 mL, 3.79 mmol). The mixture was cooled to 0° C. before TiCl4 solution (1M DCE, 0.55 mL, 0.55 mmol) was added dropwise via syringe pump over 30 min. The reaction was allowed to warm to room temperature and then heated at 50° C. for 6 h. The mixture was then diluted with DCM (15 mL) and quenched with NaHCO3 (aqueous saturated, 5 mL). Upon vigorous shaking, the organic phase was separated using a PTFE phase separator and dried over Na2SO4. Removal of the solvent afforded N-(1-(4-(benzyloxy)-1-methyl-1H-indol-5-yl)butylidene)-2-methylpropan-2-amine as a yellow oil, which was taken directly into next step without purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([O:12][CH3:13])[CH:11]=1)[C:6](Cl)=[O:7].C[O:15][P:16]1[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[C:19]2[CH:26]=[CH:27][CH:28]=[CH:29][C:18]=2[O:17]1>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([O:12][CH3:13])[CH:11]=1)[C:6]([P:16]1(=[O:15])[C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=2[C:19]2[CH:26]=[CH:27][CH:28]=[CH:29][C:18]=2[O:17]1)=[O:7]
Reactant: COc1cc(OC)cc(C(=O)Cl)c1
Reactant: COP1Oc2ccccc2-c2ccccc21
Solvent: Cc1ccccc1
Product: COc1cc(OC)cc(C(=O)P2(=O)Oc3ccccc3-c3ccccc32)c1
Temperature: 115 °C

Procedure:
35.1 g (0.175 mol) of 3,5-dimethoxybenzoyl chloride were warmed to 80° C. under a nitrogen atmosphere. 40.3 g (0.175 mol) of 6-methoxy-(6H)-dibenz[c,e][1,2]oxaphosphorin were added dropwise over the course of one hour while stirring. At the same time, the temperature was gradually increased to 115° C. When the reaction was complete, 60 ml of toluene were added at 80° C. After crystallization, 49 g (74% of theory) of the abovementioned compound of melting point 140° to 142° C. were obtained.
Reaction SMILES: [Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][NH:8]2)=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=2)[N:3]=1.[H-].[Na+].Br[CH:24]([CH3:26])[CH3:25].O>CN(C=O)C>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:24]([CH3:26])[CH3:25])=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([N+:18]([O-:20])=[O:19])[CH:13]=2)[N:3]=1
Reactant: CC(C)Br
Reactant: O=[N+]([O-])c1cccc(Nc2nc(Cl)nc3[nH]cnc23)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)n1cnc2c(Nc3cccc([N+](=O)[O-])c3)nc(Cl)nc21
Reaction time: 1 h
Yield: 90.7 %

Procedure:
(2-Chloro-9H-purin-6-yl)-(3-nitro-phenyl)-amine (872 mg, 3 mmol) was dissolved in dry DMF (10 mL). NaH (122 mg, 5.1 mmol) was added in portions and the resulting mixture was stirred for 1 h. 2-Bromopropane (480 mg, 3.9 mmol) was then added and the reaction was stirred overnight at 80° C. under N2. After cooling, H2O (50 mL) was added slowly with stirring and cooling. After 1 h, precipitated product was filtered, washed with more cold H2O, and dried in vacuo to afford the title compound as a lemon-yellow powder (905 mg, 90.7%). TLC (95:5 CH2Cl2/MeOH): RF=0.46.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8]O)=[CH:4][C:3]=1[S:10]([CH3:13])(=[O:12])=[O:11].C1(P([N:28]=[N+:29]=[N-:30])(C2C=CC=CC=2)=O)C=CC=CC=1.N12CCCN=C1CCCCC2>C1(C)C=CC=CC=1>[N:28]([CH2:8][C:5]1[CH:6]=[CH:7][C:2]([CH3:1])=[C:3]([S:10]([CH3:13])(=[O:12])=[O:11])[CH:4]=1)=[N+:29]=[N-:30]
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Reactant: Cc1ccc(CO)cc1S(C)(=O)=O
Solvent: Cc1ccccc1
Solvent: C1CCC2=NCCCN2CC1
Product: Cc1ccc(CN=[N+]=[N-])cc1S(C)(=O)=O
Temperature: 25 °C
Yield: 58.9 %

Procedure:
A round bottom flask was charged with (4-methyl-3-(methylsulfonyl)phenyl)methanol (6.0 g, 30.14 mmol), toluene (70 mL). Diphenyl phosphoryl azide (7.8 mL, 36.1 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (5.3 mL, 36.1 mmol) were added at 0° C. and the reaction mixture was stirred over night at room temperature. The solvent was removed under reduced pressure and the residue was diluted with water and extracted with EtOAc. The combined organic phases were concentrated under reduced pressure and the residue was purified by column chromatography to get the title compound (4 g, 62% yield).
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][C:4]=1[CH:10]1[C:15](=[O:16])[C:14]([CH3:18])([CH3:17])[O:13][C:12]([CH3:20])([CH3:19])[C:11]1=[O:21])[CH3:2].[Cl:22][C:23]1[CH:28]=[C:27](F)[CH:26]=[CH:25][C:24]=1[N+:30]([O-:32])=[O:31].C(=O)([O-])[O-].[K+].[K+].Cl>CN(C)C=O>[Cl:22][C:23]1[CH:28]=[C:27]([CH:26]=[CH:25][C:24]=1[N+:30]([O-:32])=[O:31])[O:9][C:6]1[CH:7]=[CH:8][C:3]([CH2:1][CH3:2])=[C:4]([CH:10]2[C:15](=[O:16])[C:14]([CH3:18])([CH3:17])[O:13][C:12]([CH3:20])([CH3:19])[C:11]2=[O:21])[CH:5]=1
Reactant: CCc1ccc(O)cc1C1C(=O)C(C)(C)OC(C)(C)C1=O
Reactant: O=[N+]([O-])c1ccc(F)cc1Cl
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCc1ccc(Oc2ccc([N+](=O)[O-])c(Cl)c2)cc1C1C(=O)C(C)(C)OC(C)(C)C1=O
Temperature: 140 °C

Procedure:
A mixture of 4-(2-ethyl-5-hydroxyphenyl)-2,2,6,6-tetramethylpyran-3,5-dione (100 mg, 0.34 mmol), 2-chloro-4-fluoro-1-nitrobenzene (72 mg, 0.41 mmol), and potassium carbonate (110 mg, 0.69 mmol) in N,N-dimethylformamide (2 ml) is heated to 140° C. under microwave irradiation for 40 minutes. The mixture is cooled to room temperature, poured into 2M aqueous hydrochloric acid and extracted with ethyl acetate. The organic extract is washed with brine, dried over anhydrous magnesium sulfate, filtered and the filtrate is evaporated under reduced pressure. The residue is purified by column chromatography on silica gel to give 4-[5-(3-chloro-4-nitrophenoxy)-2-ethylphenyl]-2,2,6,6-tetramethylpyran-3,5-dione.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]2[N:12]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)[N:13]=[C:14]([CH3:15])[C:3]=12.Cl.C([OH:25])C>>[CH3:15][C:14]1[C:3]2[C:2](=[O:25])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[NH:5][C:4]=2[N:12]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)[N:13]=1
Reactant: CCO
Reactant: Cc1nn(-c2ccccn2)c2nc3ccccc3c(Cl)c12
Agent: Cl
Product: Cc1nn(-c2ccccn2)c2[nH]c3ccccc3c(=O)c12
Temperature: 25 °C
Yield: 79 %

Procedure:
To a solution of 4-chloro-3-methyl-1-(2-pyridinyl)-1H-pyrazolo[3,4-b]quinoline (34.9 g, 0.12 mol) in ethanol (500 mL) was added 6N hydrochloric acid (50 mL, 0.30 mol), and the mixture was heated under reflux for 2 hours. The solution was cooled to room temperature, and concentrated under reduced pressure. The residue was made basic by the addition of an aqueous sodium hydroxide solution, and the organic matter was extracted with chloroform. The extract was washed with saturated brine and water, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol=95:5) to give the title compound (25.8 g, 79% yield).
Reaction SMILES: [F:1][C:2]1[CH:19]=[CH:18][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][NH2:17])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.[Cl:20][C:21]1[CH:22]=[C:23]2[C:28](=O)[O:27][C:25](=[O:26])[C:24]2=[CH:30][C:31]=1[Cl:32]>C(Cl)Cl>[F:1][C:2]1[CH:19]=[CH:18][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][N:17]4[C:25](=[O:26])[C:24]5=[CH:30][C:31]([Cl:32])=[C:21]([Cl:20])[CH:22]=[C:23]5[C:28]4=[O:27])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1
Reactant: O=C1OC(=O)c2cc(Cl)c(Cl)cc21
Reactant: NCCN1CCC(c2noc3cc(F)ccc23)CC1
Solvent: ClCCl
Product: O=C1c2cc(Cl)c(Cl)cc2C(=O)N1CCN1CCC(c2noc3cc(F)ccc23)CC1
Reaction time: 2 h

Procedure:
A mixture of 2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethylamine (2.83 gm, 10.7 mmol) and 4,5-dichlorophthalic anhydride (2.56 gm, 11.93 mmol, 1.1 eq) in methylene chloride (100 ml, DCM) was stirred for 2 h, white solids precipitated and the TLC showed disappearance of the starting material. The solvent was removed, and the crude solid was loaded onto a flash chromatography column (28 gm, SiO2, sorbsil C-30, eluted with 1% MeOH in DCM; 0.5% of NH4OH was added towards the end of elution). The material thus purified weighed 2.26 gm as white crystals. Recrystallization twice from a large volume of hot ethanol (400 ml) yielded 1.57 gm of white shining crystals, m.p.=132°-134° C.
Reaction SMILES: [CH2:1]([N:6]([CH2:28][CH2:29][CH:30]([CH3:32])[CH3:31])[C:7]([C:9]1[CH:14]=[CH:13][N:12]2[N:15]=[C:16]([C:23]([O:25]CC)=[O:24])[C:17](C(OCC)=O)=[C:11]2[CH:10]=1)=[O:8])[CH2:2][CH:3]([CH3:5])[CH3:4].S(=O)(=O)(O)O>>[CH2:28]([N:6]([CH2:1][CH2:2][CH:3]([CH3:5])[CH3:4])[C:7]([C:9]1[CH:14]=[CH:13][N:12]2[N:15]=[C:16]([C:23]([OH:25])=[O:24])[CH:17]=[C:11]2[CH:10]=1)=[O:8])[CH2:29][CH:30]([CH3:32])[CH3:31]
Reactant: CCOC(=O)c1nn2ccc(C(=O)N(CCC(C)C)CCC(C)C)cc2c1C(=O)OCC
Agent: O=S(=O)(O)O
Product: CC(C)CCN(CCC(C)C)C(=O)c1ccn2nc(C(=O)O)cc2c1
Yield: 106.8 %

Procedure:
Diethyl 5-(diisopentylcarbamoyl)pyrazolo[1,5-a]pyridine-2,3-dicarboxylate (0.35 g, 0.786 mmol) was added to 40% aqueous sulphuric acid (5 ml) and stirred at reflux for 3 h. The resulting suspension was cooled in an ice bath then extracted with ethyl acetate (3×25 ml). The combined organic layers were washed with brine and concentrated to afford, 0.29 g (98%) of the title compound as a white solid. LCMS m/z 346.2 (M+H)+. ret. time=2.57 min.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[C:8]([O:10][CH3:11])[C:5]([CH:6]=O)=[C:4]([OH:12])[CH:3]=1.CN(C)C=O.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:25][C:26](=[O:28])[CH3:27]>>[Cl:1][C:2]1[CH:9]=[C:8]([O:10][CH3:11])[C:5]2[CH:6]=[C:25]([C:26](=[O:28])[CH3:27])[O:12][C:4]=2[CH:3]=1
Reactant: CC(=O)CCl
Reactant: COc1cc(Cl)cc(O)c1C=O
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: COc1cc(Cl)cc2oc(C(C)=O)cc12
Temperature: 65 °C
Yield: 66.4 %

Procedure:
A stirred solution of 4-chloro-2-hydroxy-6-methoxybenzaldehyde (Example 37B, 1.79 g, 9.59 mmol) in N,N-dimethylformamide (15 mL, 9.59 mmol) was charged with cesium carbonate (3.75 g, 11.51 mmol) and 1-chloropropan-2-one (0.975 mL, 11.51 mmol). The reaction mixture was heated in a sealable vessel at 65° C. for 7 hours, was filtered over a Whatman filter paper to remove insolubles rinsing with DCM then washed with sat. NaHCO3. The organic phase was dried (MgSO4), filtered and concentrated to dryness. The residue was purified by ISCO using hexanes/EtOAc as eluent. Fractions containing the desired product were concentrated to give the title material (1.43 g, 6.37 mmol, 66% yield) as a light yellow solid. LC (Method A): 1.952 min. LCMS (APCI) calcd for C11H10ClO3 [M+H]+ m/z 225.03. found 225.0. 1H NMR (CDCl3, 400 MHz) δ ppm: 7.94 (d, J=0.8 Hz, 1H), 7.49 (dd, J=0.8, 1.6 Hz, 1H), 6.97 (d, J=1.6 Hz, 1H), 3.97 (s, 3H).
Reaction SMILES: P(Br)(Br)([Br:3])=O.CN(C=O)C.[Br:11][C:12]1[CH:19]=[C:18]([CH2:20]O)[CH:17]=[CH:16][C:13]=1[CH:14]=[O:15].C([O-])(O)=O.[Na+]>C(Cl)Cl>[Br:11][C:12]1[CH:19]=[C:18]([CH2:20][Br:3])[CH:17]=[CH:16][C:13]=1[CH:14]=[O:15]
Reactant: O=Cc1ccc(CO)cc1Br
Reactant: O=P(Br)(Br)Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CN(C)C=O
Product: O=Cc1ccc(CBr)cc1Br
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 113.1 %

Procedure:
To a stirring cold (0° C.) solution of POBr3 (0.6 mol, 171 g) in CH2Cl2 (1.6 L) was added dropwise DMF (0.75 L) over a period of 1 h. A solution of 2-bromo-4-hydroxymethyl-benzaldehyde (0.49 mol, 107 g) in CH2Cl2 (0.75 L) was then added dropwise over a period of 0.5 h. The resulting mixture was stirred at 0° C. for another 0.5 h and was then transferred via a cannula to a cold (0° C.) stirring aqueous solution of NaHCO3 (3 L, 1M) while maintaining the temperature of the aqueous solution below 10° C. After the transfer was completed, the mixture was extracted with CH2Cl2 (2 L). The organic extract was separated and washed with H2O (3 L) and brine (3 L), dried with MgSO4 (anhyd.) and concentrated to give an oil . The residue was extracted with 10% EtOAc/hexane (2 L). The organic extract was washed with H2O (2×1 L), dried with MgSO4 (anhyd.) and concentrated to a solid which was swished with hexane to give 154 g (˜100%) of the title compound as a beige solid.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[C:5]([CH3:14])=[C:4]([CH3:15])[N:3]=1.[NH3:16].C(O)C>>[NH2:16][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[C:5]([CH3:14])=[C:4]([CH3:15])[N:3]=1
Reactant: N
Reactant: CCCCCNc1nc(Cl)nc(C)c1C
Solvent: CCO
Product: CCCCCNc1nc(N)nc(C)c1C
Reaction time: 10 h
Yield: 3.5 %

Procedure:
A mixture of N-(2-chloro-5,6-dimethylpyrimidine-4-yl)-N-pentylamine (131 mg, 0.575 mmol) and 5M ammonia-ethanol (40 ml) was kept at 170° C. for 10 hours. The reaction mixture was concentrated in vacuo, purified by preparative TLC (20% MeOH/CHCl3) to give the object compound (4.2 mg, 3.5%).
Reaction SMILES: C([Sn](CCCC)(CCCC)[C:6]1[CH:7]=[C:8]([CH:15]2[O:20][CH2:19][CH2:18][CH2:17][O:16]2)[C:9]2[O:13][CH:12]=[CH:11][C:10]=2[CH:14]=1)CCC.Br[C:30]1[N:34]([CH3:35])[N:33]=[CH:32][N:31]=1>C1(C)C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[O:20]1[CH2:19][CH2:18][CH2:17][O:16][CH:15]1[C:8]1[C:9]2[O:13][CH:12]=[CH:11][C:10]=2[CH:14]=[C:6]([C:30]2[N:34]([CH3:35])[N:33]=[CH:32][N:31]=2)[CH:7]=1
Reactant: CCCC[Sn](CCCC)(CCCC)c1cc(C2OCCCO2)c2occc2c1
Reactant: Cn1ncnc1Br
Agent: Cl[Pd]Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Product: Cn1ncnc1-c1cc(C2OCCCO2)c2occc2c1
Yield: 35.2 %

Procedure:
A mixture of tributyl-(7-[1,3]dioxan-2-ylbenzofuran-5-yl)stannane (839 mg), 5-bromo-1-methyl-1H-[1,2,4]triazole (396 mg), bis(triphenylphosphine)palladium (II) chloride (59 mg) in dry toluene (10 ml) was heated at reflux for 42 h. The cooled solution was then filtered through Hyflo and the filtrate washed with 10% potassium fluoride solution (30 ml). The organic layer was washed with brine (30 ml), dried, and evaporated in vacuo to give a yellow oil. The crude material was purified by FCC eluting with hexane:ethyl acetate (1:1→1:3) to give the title compound as a yellow oil (171 mg,).
Reaction SMILES: [Li]CCCC.Br[C:7]1[CH:28]=[CH:27][CH:26]=[CH:25][C:8]=1[CH:9]=[C:10]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[CH2:14][CH2:13][C:12]2[CH:21]=[CH:22][CH:23]=[CH:24][C:11]1=2.[B:29](OC(C)C)([O:34]C(C)C)[O:30]C(C)C.Cl>C1COCC1>[CH:21]1[C:12]2[CH2:13][CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[C:10](=[CH:9][C:8]3[CH:25]=[CH:26][CH:27]=[CH:28][C:7]=3[B:29]([OH:34])[OH:30])[C:11]=2[CH:24]=[CH:23][CH:22]=1
Reactant: Brc1ccccc1C=C1c2ccccc2CCc2ccccc21
Reactant: CC(C)OB(OC(C)C)OC(C)C
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: OB(O)c1ccccc1C=C1c2ccccc2CCc2ccccc21
Temperature: -78 °C
Reaction time: 0.5 h

Procedure:
Add n-BuLi (1.6M in hexanes, 12.98 Ml, 20.76 mmol) portionwise (exothermic) to a solution of 5-(2-bromo-benzylidene)-10,11-dihydro-5H-dibenzo[a,d]cycloheptene (5.00 g, 13.84 mmol) in dry THF (50 Ml) at −78° C. under N2. Let stir at −78° C. for 30 min, then add triisopropyl borate (5.21 g, 27.68 mmol) and warm up to room temperature overnight. Add 50 Ml 1.00N HCl and stir for 15 min. Extract into ethyl acetate, dry (MgSO4) and concentrate organics to a brown foam. Recrystallize from boiling hexanes, then chromatograph on silica gel (40 g), eluting with 20% to 50% ethyl acetate/hexanes to afford the title compound as a white foam, mp 134.1° C. MS (ES) 325 (M−H); HPLC shows 82% purity.
Reaction SMILES: [C:1]([O:4][CH2:5][C:6]1[NH:15][C:14](=[O:16])[C:13]2[C:8](=[CH:9][C:10]([Cl:18])=[C:11]([CH3:17])[CH:12]=2)[N:7]=1)(=[O:3])[CH3:2].[H-].[Na+].I[CH3:22]>CN(C=O)C.ClCCl>[C:1]([O:4][CH2:5][C:6]1[N:15]([CH3:22])[C:14](=[O:16])[C:13]2[C:8](=[CH:9][C:10]([Cl:18])=[C:11]([CH3:17])[CH:12]=2)[N:7]=1)(=[O:3])[CH3:2]
Reactant: CI
Reactant: CC(=O)OCc1nc2cc(Cl)c(C)cc2c(=O)[nH]1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: CC(=O)OCc1nc2cc(Cl)c(C)cc2c(=O)n1C
Reaction time: 0.02 h
Yield: 66.8 %

Procedure:
To a suspension of 2-acetoxymethyl-7-chloro-6-methyl-3,4-dihydroquinazolin-4-one 0.428 g, 1.6 mmol) in anhydrous DMF (13 ml) was added sodium hydride (60% dispersion, 0.070 g, 1.76 mmol) under argon. Stirring was continued at room temperature for 1 min and then iodomethane (0.20 ml, 3.2 mmol) was added into the reaction mixture with a syringe via a septum. Stirring was continued at room temperature for 1 hour and the reaction mixture was then partitioned between ethyl acetate (130 ml) and brine (80 ml). The organic layer was washed with dilute brine (80 ml), dried (Na2SO4) and concentrated in vacuo to leave an orange residue. This orange residue was dissolved in dichloromethane and to this solution silica gel (Art 7734, 1.7 g) was added. The solvent was removed in vacuo and the orange free running powder was placed on a silica gel column made up in 5% ethyl acetate in dichloromethane. The column was eluted with 5% ethyl acetate in dichloromethane to afford a pale yellow solid (0.300 g, 67%), mp 110-112° C.; 1H-NMR (DMSO-d6) 2.17 (s, 3H, CH3CO), 2.47 (s, 3H, 6-CH3), 3.54 (s, 3H, N3—CH3), 5.23 (s, 2H, 2-CH2O), 7.71, 8.09 (2×s, 2H, 5-H, 8-H).
Reaction SMILES: [C:1]1([C:7]2[C:8](=[O:18])[O:9][C:10]3[C:15]([C:16]=2[OH:17])=[CH:14][CH:13]=[CH:12][CH:11]=3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N:19]1([CH2:25][CH:26]([CH3:29])[CH2:27]Cl)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1>CCCCCC>[N:19]1([CH2:25][CH:26]([CH3:29])[CH2:27][O:17][C:16]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[O:9][C:8](=[O:18])[C:7]=2[C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1
Reactant: CC(CCl)CN1CCCCC1
Reactant: O=c1oc2ccccc2c(O)c1-c1ccccc1
Solvent: CCCCCC
Product: CC(COc1c(-c2ccccc2)c(=O)oc2ccccc12)CN1CCCCC1
Yield: 77.5 %

Procedure:
Prepared from 3-phenyl-4-hydroxy-coumarin and 3-piperidino-2-methyl-1-chloropropane, according to the method of Example 8. A light yellow solid is obtained. M.P. 86°-87° C. (hexane). Yield 77.5%.
Reaction SMILES: [CH3:1][O:2][N:3]=[CH:4]/[C:5](/[CH3:16])=[CH:6]/[C@@H:7]1[C@@H:9]([C:10]([O:12]C)=[O:11])[C:8]1([CH3:15])[CH3:14].[OH-].[Na+].CO>O>[CH3:1][O:2][N:3]=[CH:4]/[C:5](/[CH3:16])=[CH:6]/[C@@H:7]1[C@@H:9]([C:10]([OH:12])=[O:11])[C:8]1([CH3:15])[CH3:14]
Reactant: CON=C/C(C)=C/[C@@H]1[C@@H](C(=O)OC)C1(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: CON=C/C(C)=C/[C@@H]1[C@@H](C(=O)O)C1(C)C
Temperature: 60 °C
Reaction time: 3 h
Yield: 59.9 %

Procedure:
Under nitrogen atmosphere, a mixture of 0.57 g of methyl (1R)-trans-3-[(E)-3-methoxyimino-2-methyl-1-propenyl]-2,2-dimethylcyclopropanecarboxylate, 7.5 ml of 1 mol/L sodium hydroxide aqueous solution and 7.5 ml of methanol was stirred at 60° C. for 3 hours. Then, water was added to the reaction mixture, and the mixture was washed with diethyl ether. 1 mol/L hydrochloric acid was added to the resultant aqueous layer to make the layer acidic, and extraction with diethyl ether was performed, then, the organic layer was dried over anhydrous magnesium sulfate, then, filtrated. The filtrate was concentrated under reduced pressure, then, the residue was subjected to silica gel column chromatography to obtain 0.32 g of (1R)-trans-3-[(E)-3-methoxyimino-2-methyl-1-propenyl]-2,2-dimethylcyclopropanecarboxylic acid:
Reaction SMILES: [C:1]([O:5][C:6]1[C:11]([F:12])=[C:10]([F:13])[N:9]=[C:8]([F:14])[C:7]=1Cl)([CH3:4])([CH3:3])[CH3:2].[H][H]>CO.[OH-].[OH-].[Pd+2]>[C:1]([O:5][C:6]1[CH:7]=[C:8]([F:14])[N:9]=[C:10]([F:13])[C:11]=1[F:12])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)Oc1c(F)c(F)nc(F)c1Cl
Reactant: [H][H]
Agent: [Pd+2]
Agent: [OH-]
Solvent: CO
Product: CC(C)(C)Oc1cc(F)nc(F)c1F
Reaction time: 22 h
Yield: 56470.9 %

Procedure:
To 4-t-butoxy-3-chloro-2,5,6-trifluoropyridine (24.92 g, 0.104 mmol) in 100 mL of methanol was added 2.5 g of Pearlman's catalyst (Aldrich Chemical Co.), and the mixture was stirred at ambient temperature for 14 hours under and atmosphere of hydrogen. An additional 2.5 g of catalyst was added, and the mixture was stirred for another 22 hours. The mixture was filtered, the filtrate was concentrated, and the residue was extracted with hexane/ether. After filtration, the solvent was removed by evaporation, and the residue was purified by flash chromatography (ethyl acetate:hexane 1:16) to yield 12.05 g of 4-t-butoxy-2,3,6-trifluoropyridine. MS 206 (M+H)+, 233 (M+18)+ ; 1H NMR (CDCl3)∂: 1.52 (s, 9H), 6.5 (m, 1H); 19F NMR (CDCl3, CFCl3 as reference)∂: 72.60 (dd, J1 =14.3, J2 =21.0 Hz), 89.74 (dd, J1 =14.3, J2 =21.0 Hz), 164.68 (dt, J1 =4.2, J2 =21.0 Hz).
Reaction SMILES: [H-].[Na+].[NH:3]1[CH:7]=[N:6][CH:5]=[N:4]1.[O:8]1[CH2:13][CH2:12][CH2:11][CH2:10][CH:9]1[O:14][CH:15]([C:17]1([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=2[F:27])[CH2:19][O:18]1)[CH3:16]>CN(C)C=O>[F:27][C:21]1[CH:22]=[C:23]([F:26])[CH:24]=[CH:25][C:20]=1[C:17]([OH:18])([CH:15]([O:14][CH:9]1[CH2:10][CH2:11][CH2:12][CH2:13][O:8]1)[CH3:16])[CH2:19][N:3]1[CH:7]=[N:6][CH:5]=[N:4]1
Reactant: c1nc[nH]n1
Reactant: CC(OC1CCCCO1)C1(c2ccc(F)cc2F)CO1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(OC1CCCCO1)C(O)(Cn1cncn1)c1ccc(F)cc1F
Temperature: 0 °C
Yield: 49.6 %

Procedure:
To N,N-dimethylformamide (700 ml) was added, at room temperature while stirring, 60% sodium hydride in oil (35.2 g) by portions during 10 minutes. The mixture was stirred for 5 minutes at room temperature, to which was added 1H-1,2,4-triazole (25 g) by portions at room temperature during 20 minutes. The reaction mixture was cooled with ice, to which was added 1H-1,2,4-triazole (44.6 g) during 30 minutes with stirring, followed by stirring at room temperature for further 10 minutes. To the resultant mixture was added dropwise 2-[1-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)ethyl]-2-(2,4-difluorophenyl)oxirane (83.4 g) during 5 minutes, which was stirred for 4 hours at 90° C. The reaction mixture was cooled and poured into ice-water (1.5 l), which was subjected to extraction with ethyl acetate (500 ml) for 4 times. The ethyl acetate layer was washed with water (300 ml) 3 times and dried over anhydrous magnesium sulfate. Then the solvent was distilled off to leave a pale yellow oily product. This product was purified by means of a silica gel column chromatography (hexane:acetone=4:1~1:1). The resultant oily product was crystallized from hexane to give 2-(2,4-difluorophenyl)-3-(3,4,5,6-tetrahydro-2H-pyran-2-yl)oxy-1-(1H-1,2,4-triazol-1-yl)-2-butanol (51.4 g) as colorless powder, m.p. 93°-95° C. Elemental Analysis for C17H21F2N3O3 : Calcd.: C, 57.78; H, 5.99; N, 11.89 Found: C, 57.82; H, 6.04; N, 11.77.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:22])[CH2:4][CH2:5][C:6]1[CH:11]=[C:10]([C:12](=[O:14])[CH3:13])[CH:9]=[CH:8][C:7]=1OCCCCCO.C(N(CC)CC)C.CS(Cl)(=O)=O>C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:22])[CH2:4][CH2:5][C:6]1[CH:11]=[C:10]([C:12](=[O:14])[CH3:13])[CH:9]=[CH:8][CH:7]=1
Reactant: COC(=O)CCc1cc(C(C)=O)ccc1OCCCCCO
Agent: CS(=O)(=O)Cl
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: COC(=O)CCc1cccc(C(C)=O)c1
Temperature: 0 °C
Reaction time: 1.33 h

Procedure:
A solution of 0.62 g (2 mmol) of 2-[(5-hydroxypentyl)oxy]-5-acetylbenzenepropanoic acid methyl ester and 2 mL of triethylamine, in 6 mL of ethyl acetate was stirred with ice-bath cooling while 0.6 mL of methanesulfonyl chloride was added dropwise. The resulting mixture was stirred at 0°-5° C. for 1.33 hr and then poured into ice--3N HCl. Work-up with ethyl acetate in the usual manner gave 0.96 g of 2-[[5-(methylsulfonyl)oxy]pentyl]oxy]-5-acetylbenzenepropanoic acid methyl ester as an oil which was used without further purification.