Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CS(C)=O.C(Cl)(=O)C(Cl)=O.[C:11]1([C@H:17]2[CH2:21][N:20]([C:22](=[O:27])[C:23]([F:26])([F:25])[F:24])[CH2:19][C@@H:18]2[CH2:28][OH:29])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[Cl-].[NH4+]>ClCCl.C(N(CC)CC)C>[C:11]1([C@H:17]2[CH2:21][N:20]([C:22](=[O:27])[C:23]([F:25])([F:26])[F:24])[CH2:19][C@@H:18]2[CH:28]=[O:29])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: O=C(N1C[C@H](CO)[C@@H](c2ccccc2)C1)C(F)(F)F
Agent: O=C(Cl)C(=O)Cl
Agent: [Cl-]
Agent: [NH4+]
Solvent: CS(C)=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C[C@H]1CN(C(=O)C(F)(F)F)C[C@@H]1c1ccccc1
Temperature: -25 °C
Reaction time: 0.25 h

Procedure:
A 7.18 g portion of DMSO was dissolved in 30 ml of dichloromethane, and a 10 ml dichloromethane solution of 4.0 ml oxalyl chloride was added thereto while keeping the internal temperature at −60° C. or less. After stirring for 15 minutes, a 40 ml dichloromethane solution of 6.28 g of [(3R,4S)-4-phenyl-1-(trifluoroacetyl)pyrrolidin-3-yl]methanol was added thereto while keeping the inner temperature at −60° C. and stirred for 15 minutes. A 19.3 ml portion of triethylamine was added to the reaction solution while keeping the internal temperature at −50° C. or less, and then the internal temperature was allowed to warm to −25° C. over 30 minutes or more, and this was further stirred at −25° C. for 20 minutes. Under ice-cooling, the reaction solution was added to saturated ammonium chloride aqueous solution to quench the reaction, and extracted with diethyl ether. The organic layer was washed with water and saturated brine in that order and dried with anhydrous sodium sulfate. By concentrating under a reduced pressure, (3R,4S)-4-phenyl-1-(trifluoroacetyl)pyrrolidine-3-carbaldehyde was obtained as a crude product.
Reaction SMILES: [CH3:1][N:2]1[CH:11]2[C:6]([CH3:17])([C:7]3[CH:15]=[CH:14][C:13]([SH:16])=[CH:12][C:8]=3[CH2:9][CH2:10]2)[CH2:5][CH2:4][C:3]1=[O:18].C(=O)([O-])[O-].[K+].[K+].Cl[C:26]1[N:31]=[CH:30][CH:29]=[CH:28][N:27]=1.CN(C)C=O>C(OCC)(=O)C>[CH3:1][N:2]1[C@H:11]2[C@@:6]([CH3:17])([C:7]3[CH:15]=[CH:14][C:13]([S:16][C:26]4[N:31]=[CH:30][CH:29]=[CH:28][N:27]=4)=[CH:12][C:8]=3[CH2:9][CH2:10]2)[CH2:5][CH2:4][C:3]1=[O:18]
Reactant: Clc1ncccn1
Reactant: CN1C(=O)CCC2(C)c3ccc(S)cc3CCC12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CN1C(=O)CC[C@]2(C)c3ccc(Sc4ncccn4)cc3CC[C@@H]12
Yield: 23.3 %

Procedure:
A 15 mL round bottom flask was charged with (+)-(4aR)-10bR)-4-methyl-8-mercapto-10b-methyl-1,2,3,4,4a,-5,6,10b-octahydrobenzo[f]quinolin-3-one (100 mg, 0.38 mmol), potassium carbonate (158 mg, 1.14 mmol), 2-chloropyrimidine (53 mg, 0.46 mmol) and 1 mL of anhydrous dimethylformamide, fitted with a reflux condenser, and the stirred mixture was heated at 60°, under nitrogen, for 18 h. The mixture was cooled, diluted with ethyl acetate (75 mL) and washed with brine (2×25 mL). The combined organic extracts were dried over sodium sulfate, concentrated, and purified by silica gel chromatography (ethyl acetate eluent) to give 30 mg (23%) of the title compound as an oil. FDMS: m/e=339.
Reaction SMILES: [CH3:1][CH2:2][O:3][C:4]([C:6]1[C:11]([CH3:13])([CH3:12])[CH2:10][CH2:9][CH2:8][C:7]=1[CH3:14])=[O:5].C1(=O)OC(=[O:19])C=C1.[H][H]>>[CH3:14][C:7]12[O:19][C:6]1([C:4]([O:3][CH2:2][CH3:1])=[O:5])[C:11]([CH3:13])([CH3:12])[CH2:10][CH2:9][CH2:8]2
Reactant: [H][H]
Reactant: CCOC(=O)C1=C(C)CCCC1(C)C
Reactant: O=C1C=CC(=O)O1
Product: CCOC(=O)C12OC1(C)CCCC2(C)C
Yield: 90 %

Procedure:
98.0 g (0.5 M) of ethyl β-cyclogeraniate have been treated, as described in Example 1, with maleic anhydride and hydrogen peroxyde to give the desired ester with a yield of 90%, b.p. 55°/0.1 Torr:
Reaction SMILES: C(O)C.[Br:4][C:5]1[C:6]([CH3:16])=[C:7]([N+:13]([O-:15])=[O:14])[C:8]([O:11][CH3:12])=[N:9][CH:10]=1.[C:17](OCC)(=[O:23])[C:18]([O:20][CH2:21][CH3:22])=[O:19].[O-]CC.[K+]>C(OCC)(=O)C.CCOCC>[Br:4][C:5]1[C:6](/[CH:16]=[C:17](\[OH:23])/[C:18]([O:20][CH2:21][CH3:22])=[O:19])=[C:7]([N+:13]([O-:15])=[O:14])[C:8]([O:11][CH3:12])=[N:9][CH:10]=1
Reactant: COc1ncc(Br)c(C)c1[N+](=O)[O-]
Reactant: CCOC(=O)C(=O)OCC
Agent: CC[O-]
Agent: [K+]
Solvent: CCO
Solvent: CCOC(C)=O
Solvent: CCOCC
Product: CCOC(=O)/C(O)=C/c1c(Br)cnc(OC)c1[N+](=O)[O-]
Temperature: 45 °C
Yield: 45.6 %

Procedure:
To a solution of ethanol (15 mL) and ether (150 mL) were added 5-bromo-2-methoxy-4-methyl-3-nitropyridine (14.82 g, 60 mmol), diethyl oxalate (13.15 g, 90 mmol), and potassium ethoxide (6.06 g, 72 mmol). The reaction mixture was heated at 45° C. for 24 hours. During the reaction, the flask was shaken by hand several times. After cooling, the reaction mixture was partitioned between water and ethyl acetate. The aqueous layer was extracted with additional ethyl acetate three times. The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified by flash chromatography on silica gel eluting with 10-20% ethyl acetate in hexanes to 9.5 g of the title compound (yield 46%).
Reaction SMILES: [CH2:1]([S:3][CH2:4][CH:5]([CH2:11][CH:12]([CH3:14])[CH3:13])[C:6]([O:8]CC)=[O:7])[CH3:2].O.Cl>CCCCCC.C(OCC)(=O)C.[OH-].[K+]>[CH2:1]([S:3][CH2:4][CH:5]([CH2:11][CH:12]([CH3:13])[CH3:14])[C:6]([OH:8])=[O:7])[CH3:2]
Reactant: CCOC(=O)C(CSCC)CC(C)C
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CCCCCC
Product: CCSCC(CC(C)C)C(=O)O
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 101.9 %

Procedure:
650 mg of ethyl 2-ethylthiomethyl-4-methylpentanoate was dissolved in 6 ml of an ethanol/water (10/1) solution, 8.9 ml of an ethanol/water (10/1) solution of 2N potassium hydroxide was added thereto. The solution was stirred at room temperature for 2.5 hours, and then, the reaction solution was distilled off under reduced pressure to obtain a suspension. To this suspension, 40 ml of water was added, and the reaction solution was adjusted to pH2 with 2N hydrochloric acid under cooling with ice, and extracted with ethyl acetate. The ethyl acetate layer was washed with water and then with a saturated sodium chloride aqueous solution and dried over anhydrous sodium sulfate. Then, the solvent was distilled off to obtain 577 mg of 2-ethylthiomethyl-4-methylpentanoic acid as colorless oily substance.
Reaction SMILES: [Br:1][C:2]1[C:11]([NH:12][C:13]2[NH:14][CH2:15][CH2:16][N:17]=2)=[CH:10][CH:9]=[C:8]2[C:3]=1[NH:4][C:5](=O)[C:6]([CH3:19])([CH3:18])[NH:7]2>O1CCCC1>[Br:1][C:2]1[C:11]([NH:12][C:13]2[NH:14][CH2:15][CH2:16][N:17]=2)=[CH:10][CH:9]=[C:8]2[C:3]=1[NH:4][CH2:5][C:6]([CH3:19])([CH3:18])[NH:7]2
Reactant: CC1(C)Nc2ccc(NC3=NCCN3)c(Br)c2NC1=O
Solvent: C1CCOC1
Product: CC1(C)CNc2c(ccc(NC3=NCCN3)c2Br)N1
Temperature: 0 °C

Procedure:
A suspension of 5-bromo-1,2-dihydro-2,2-dimethyl-6-(2-imidazolin-2-ylamino)-3-(4H)-quinoxalinone (150 mg, 0.45 mmol) and LiALH4 (17 mg, 0.45 mmol) in tetrahydrofuran (3 ml) is heated and maintained at a temperature of 50°-80° C. until the starting material is consumed. The mixture is cooled to 0° C., 2-3 drops of H2O is added and the mixture is filtered. The solution is concentrated in vacuo to yield a residue which is chromatographed on silica gel with CHCl3 : CH3OH saturated with NH3 (g) elution to produce the title compound.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]#[C:18][C:19]([OH:27])([C:21]4[N:26]=[CH:25][CH:24]=[CH:23][N:22]=4)[CH3:20])[CH:15]=3)[C:10]([C:28]([OH:30])=O)=[N:9]2)[CH:5]=[CH:4][N:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(O)(=O)C(O)=O.[CH2:61]1[C:64]2([CH2:67][NH:66][CH2:65]2)[CH2:63][O:62]1.C(N(CC)CC)C>CN(C=O)C.O>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]#[C:18][C:19]([C:21]4[N:26]=[CH:25][CH:24]=[CH:23][N:22]=4)([OH:27])[CH3:20])[CH:15]=3)[C:10]([C:28]([N:66]3[CH2:67][C:64]4([CH2:61][O:62][CH2:63]4)[CH2:65]3)=[O:30])=[N:9]2)[CH:5]=[CH:4][N:3]=1
Reactant: C1NCC12COC2
Reactant: CC(O)(C#Cc1ccc2c(C(=O)O)nn(-c3ccnc(N)n3)c2c1)c1ncccn1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Agent: O=C(O)C(=O)O
Solvent: O
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CC(O)(C#Cc1ccc2c(C(=O)N3CC4(COC4)C3)nn(-c3ccnc(N)n3)c2c1)c1ncccn1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of 1-(2-aminopyrimidin-4-yl)-6-[3-hydroxy-3-(pyrimidin-2-yl)but-1-yn-1-yl]indazole-3-carboxylic acid (100 mg, 0.25 mmol) in DMF (2 ml) was added HATU (189.46 mg, 0.5 mmol) followed by 2-oxa-6-azaspiro[3.3]heptane oxalate (94.26 mg, 0.5 mmol) and triethylamine (0.1 ml, 0.75 mmol). The reaction mixture was stirred at RT for 16 hr. Water (2 ml) was added to the reaction mixture and the product extracted into EtOAc (2×5 ml). The combined organics were washed with water (3 mL) and brine (3 mL) and concentrated in vacuo. The crude product was purified twice by flash chromatography (Biotage, 2-12% methanol in DCM) to give the title compound: 1H NMR (500 MHz, DMSO) delta 1.93 (3H, s), 4.31 (2H, s), 4.74 (4H, q, J=6.9 Hz), 4.87 (2H, s), 6.26 (1H, s), 7.02-7.32 (3H, m), 7.41 (1H, dd, J=8.4, 1.2 Hz), 7.51 (1H, t, J=4.9 Hz), 8.23 (1H, d, J=8.0 Hz), 8.39 (1H, d, J=5.5 Hz), 8.75-9.10 (3H, m); LC-MS: m/z=+483.10 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[NH:9][C:10]2[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=2[N:12]=1.C(=O)([O-])[O-].[K+].[K+].[C:23](Cl)(=[O:26])[CH2:24][CH3:25]>C(#N)C>[NH:12]1[C:11]2[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=2[N:9]=[C:8]1[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[NH:1][C:23](=[O:26])[CH2:24][CH3:25]
Reactant: Nc1ccccc1-c1nc2ccccc2[nH]1
Reactant: CCC(=O)Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCC(=O)Nc1ccccc1-c1nc2ccccc2[nH]1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution/suspension of 2-(2-aminophenyl) benzimidazole (5.0 g, 23.0 mmol), potassium carbonate (9.5 g, 69.0 mmol) in acetonitrile (300 mL) at 0° C. was added propionyl chloride (2.3 g, 23.0 mmol). The reaction mixture was allowed to warm to room temperature, stir overnight, followed by filtration to remove the white solid. This was washed thoroughly with acetonitrile. The acetonitrile was concentrated in vacuo, the residue extracted into methylene chloride, washed with potassium carbonate (saturated solution) and the organic layer was dried over anhydrous magnesium sulfate. The methylene chloride was removed in vacuo and the resulting solid was recrystallized from methanol, m.p. >200° C. 1H NMR (300 MHz, DMSO-d6) δ13.14 (bs, 1H), 13.00 (s, 1H), 8.70 (d, J=8.4 Hz, 1H), 8.10 (d, J=8.0 Hz, 1H), 7.71 (d, J=7.2 Hz, 1H), 7.57 (d, J=8.3 Hz, 1H), 7.46 (t, J=8.0 Hz, 1H), 7.31-7.20 (m, 3H), 2.53 (q, J=7.5 Hz, 2H), 1.23 (t, J=7.5 Hz, 313C NMR (75 MHz, DMSO-d6) δ172.2, 150.9, 172.1, 138.4, 133.4, 130.7, 127.3, 123.5, 122.7, 122.3, 119.8, 118.6, 115.2, 111.5, 31.1, 9.6; IR (KBr)3262, 1662 cm-1 ; MS (DCI) m/e MH+ =266; Analysis calc'd for C16H15N3O1 /0.4H2O1 : C, 70.53; H, 5.64; N, 15.37; H2O1, 2.40; found: C, 70.52; H, 5.84; N, 15.42; H2O1, 2.64.
Reaction SMILES: [CH2:1]=[C:2]1[CH2:5][CH:4]([C:6]([OH:8])=[O:7])[CH2:3]1.C([N:11](CC)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.[CH2:33](O)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1>C1(C)C=CC=CC=1.CCOCC>[CH2:33]([O:7][C:6]([C:4]1([NH2:11])[CH2:5][C:2](=[CH2:1])[CH2:3]1)=[O:8])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1
Reactant: C=C1CC(C(=O)O)C1
Reactant: CCN(CC)CC
Reactant: OCc1ccccc1
Agent: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Solvent: Cc1ccccc1
Solvent: CCOCC
Product: C=C1CC(N)(C(=O)OCc2ccccc2)C1
Temperature: 80 °C
Reaction time: 1 h
Yield: 68.5 %

Procedure:
To a stirred solution of 26.7 g (238 mmol) of 3-methylenecyclobutane carboxylic acid (Cripps, H. N.; Williams, J. K.; Sharkey, W. H. J. Am. Chem. Soc. 1959, 81, 2723-2728) in 100 mL of toluene at 0° C. was added 36.4 mL (262 mmol) of triethylamine and then 72.1 g (262 mmol) of diphenylphosphoryl azide. The reaction mixture was then heated at 80° C., and after 1 h, 28.33 g (262 mmol) of benzyl alcohol was added. After 15 h at 85° C., the cooled reaction mixture was poured into 1 L of ether, washed with saturated aqueous NaHCO3, and then saturated aqueous NaCl, dried over MgSO4, and then concentrated under reduced pressure. Chromatography of the residue in three portions on 1400 g of silica gel with 80:20/hexane:EtOAc afforded 35.4 g (63%) of the desired compound.
Reaction SMILES: [Cl-].[Cl-].[Cl-].[Al+3].C([N:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]([C:21]([NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([CH:32]3[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]3)=[O:31])[N:25]=2)=[O:22])=[CH:13]1)C1C=CC=CC=1>C1C=CC=CC=1.C(OCC)(=O)C>[NH:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]([C:21]([NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([CH:32]3[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]3)=[O:31])[N:25]=2)=[O:22])=[CH:13]1
Reactant: CN1CCC(C(=O)c2cccc(NC(=O)c3cn(Cc4ccccc4)c4ccccc34)n2)CC1
Agent: [Al+3]
Agent: [Cl-]
Solvent: CCOC(C)=O
Solvent: c1ccccc1
Product: CN1CCC(C(=O)c2cccc(NC(=O)c3c[nH]c4ccccc34)n2)CC1
Temperature: 25 °C
Yield: 66.6 %

Procedure:
Add aluminum trichloride (106 mg, 0.795 mmol) to a suspension of 1-benzylindol-3-yl-N-[6-(1-methylpiperidin-4-ylcarbonyl)-pyridin-2-yl]-carboxamide (180 mg, 0.398 mmol) in benzene (6 mL) and heat the mixture at reflux for 1.25 hr. Then add another 2 equivalents of aluminum trichloride (108 mg) and continue heating at reflux for an additional 5.5 hr. Cool the reaction mixture to room temperature. Then pour the reaction into ice cold H2O (50 mL) and then dilute with ethyl acetate. Adjusted the pH of the solution to 11 with saturated Na2CO3, separate the layers and extract the aqueous layer with ethyl acetate (3×50 mL). Combined the organic fractions, dry with Na2SO4, filter and concentrate in vacuo. Purify the intermediate by flash chromatography on a silica gel column, eluting with CHCl3/methanol/NH4OH (93:7:1) to obtain the sub-title compound (96 mg, 67%). 1H NMR (CD3OD) 8.45 (d, J=8 Hz, 1H), 8.25 (s, 1H), 8.21 (m, 1H), 7.96 (t, J=8 Hz, 1H), 7.72 (d, J=8 Hz, 1H), 7.48 (m, 1H), 7.18-7.27 (m, 2H), 3.90 (m, 1H), 2.94-3.01 (m, 2H), 2.31 (s, 3H), 2.19-2.28 (m, 2H), 1.92-2.02 (m, 2H), 1.71-1.84 (m, 2H). CIMS (Methane) m/z 363 [C21H22N4O2+H]+.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:19])[C:4]1[CH:13]=[C:12]([O:14][CH:15]([CH3:17])[CH3:16])[CH:11]=[C:6]([C:7]([O:9][CH3:10])=[O:8])[C:5]=1[CH3:18].C1C(=O)N([Br:27])C(=O)C1.CC(N=NC(C#N)(C)C)(C#N)C>C(Cl)(Cl)(Cl)Cl>[CH3:10][O:9][C:7](=[O:8])[C:6]1[CH:11]=[C:12]([O:14][CH:15]([CH3:16])[CH3:17])[CH:13]=[C:4]([C:3]([O:2][CH3:1])=[O:19])[C:5]=1[CH2:18][Br:27]
Reactant: O=C1CCC(=O)N1Br
Reactant: COC(=O)c1cc(OC(C)C)cc(C(=O)OC)c1C
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: ClC(Cl)(Cl)Cl
Product: COC(=O)c1cc(OC(C)C)cc(C(=O)OC)c1CBr
Temperature: 85 °C
Reaction time: 0.08 h
Yield: 93 %

Procedure:
To a solution of 5-isopropoxy-2-methyl-isophthalic acid dimethyl ester (Cpd B, 14.5 g, 54.5 mmol) in CCl4 (250 mL) was added NBS (11.2 g, 60.0 mmol). After stirring the mixture at 85° C. for 5 minutes, AIBN (2.69 g, 16.4 mmol) was added. The resulting reaction mixture was stirred at 85° C. for 1 hour. The reaction mixture was chilled in an ice bath and the precipitates were filtered and discarded. The resulting filtrate was concentrated under vacuum and purified by column chromatography (0-40%, EtOAc/heptanes) to give 2-bromomethyl-5-isopropoxy-isophthalic acid dimethyl ester (Cpd C, 17.5 g, 93% yield) as a clear oil which solidified upon standing.
Reaction SMILES: [Na].Cl[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:9]1([Na])[CH:14]=CC=[CH:11][CH:10]=1.C(Cl)C=C>C1(C)C=CC=CC=1.O>[C:3]1([CH2:11][CH2:10][CH:9]=[CH2:14])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: [Na]c1ccccc1
Reactant: Clc1ccccc1
Agent: [Na]
Solvent: Cc1ccccc1
Solvent: O
Solvent: C=CCCl
Product: C=CCCc1ccccc1
Reaction time: 0.5 h
Yield: 72.2 %

Procedure:
In 220 g of toluene, 20.3 g (0.883 mol) of sodium dispersion was reacted with 46.5 g (0.413 mol) of chlorobenzene, to prepare phenyl sodium. The resultant toluene slurry was stirred for 2.5 hours under heat reflux. The thus-obtained black slurry was cooled, and then a toluene (40 g) solution containing 31.6 g (0.413 mol) of allyl chloride was added to the cooled slurry, keeping the reaction temperature in the range of from -10° C. to 0° C., and then the reaction mixture was allowed to stand, for aging, for 30 minutes at room temperature. After the reaction was completed, the reaction mixture was subjected to hydrolysis with 350 ml of water in the range of 5 to 20° C., and then the resultant organic layer was washed with 300 ml of water twice, according to a usual manner. Toluene was removed therefrom by atomospheric distillation, and the residual orange oil was subjected to distillation under reduced pressure in the same manner as in Example 7. As a result, 39.4 g (0.298 mol, yield 72.2%) of 4-phenyl-1-butene was given (purity 98.3%), and 6.3 g of a residue remained.
Reaction SMILES: [N:1]([C:4]1[CH2:5][C@@H:6]2[CH2:23][C:22](=[O:24])[N:7]2[C:8]=1[C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[CH:15][CH:14]=1)=[O:10])=[N+:2]=[N-:3].[CH2:25]([N:27]([CH2:31][CH3:32])[C:28]#[C:29][CH3:30])[CH3:26]>ClCCl>[CH2:25]([N:27]([CH2:31][CH3:32])[C:28]1[N:1]([C:4]2[CH2:5][C@@H:6]3[CH2:23][C:22](=[O:24])[N:7]3[C:8]=2[C:9]([O:11][CH2:12][C:13]2[CH:14]=[CH:15][C:16]([N+:19]([O-:21])=[O:20])=[CH:17][CH:18]=2)=[O:10])[N:2]=[N:3][C:29]=1[CH3:30])[CH3:26]
Reactant: [N-]=[N+]=NC1=C(C(=O)OCc2ccc([N+](=O)[O-])cc2)N2C(=O)C[C@H]2C1
Reactant: CC#CN(CC)CC
Solvent: ClCCl
Product: CCN(CC)c1c(C)nnn1C1=C(C(=O)OCc2ccc([N+](=O)[O-])cc2)N2C(=O)C[C@H]2C1
Yield: 15.1 %

Procedure:
A stirred, 0° C. solution of p-nitrobenzyl 2-azido-carbapen-2-em-3-carboxylate (5.9 mg, 18 micromol) in dry dichloromethane (0.30 ml) was treated with 1-diethylaminopropyne (2.5 microliter, 2.0 mg, 18 micromol). After 1.25 hours the mixture was filtered through a 6 cm×4 mm column of florisil and the eluate was evaporated under vacuum. The residue was chromatographed on one 5 cm×20 cm 250 micron silica gel thin layer chromatography plate developed with 5:1 (v/v) dichloromethane-ethyl acetate, and the band centered at Rf 0.30 was eluted with ethyl acetate. The elutate was evaporated under vacuum to provide 1.2 mg (15%) p-nitrobenzyl 2-(5-diethylamino-4-methyl-1,2,3-triazol-1-yl)carbapen-2-em-3-carboxylate; IR (CH2Cl2): 1785, 1730 cm-1 ; NMR (CDCl3): δ 0.92 t (J=7 Hz, 6H), 2.30 s (3H), 2.97 q (J=7 Hz, 4H), 3.18 dd (J1 =4 Hz, J2 =17 Hz, 1H), 3.24 dd (J1 =10 Hz, J2 =18 Hz, 1H), 3.40 dd (J1 =8 Hz, J2 =18 Hz, 1H), 3.65 dd (J1 =6 Hz, J2 =17 Hz, 1H), 4.25 m (1H), 5.22 d (J=14 Hz, 1H), 5.32 d (J=14 Hz, 1H), 7.45 d (J=9 Hz, 2H), 8.22 d (J=9 Hz); MS (m/e): 440, 414, 412, 398, 384, 369, 357, 355, 341, 333.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[CH:18][CH:17]=1.ClC(Cl)(O[C:27](=[O:33])OC(Cl)(Cl)Cl)Cl.Cl.[CH2:36]([NH2:38])[CH3:37].CO>C(Cl)(Cl)Cl.C(N(CC)CC)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[N:9]=[CH:8][N:7]=[C:6]2[O:15][C:16]1[CH:22]=[CH:21][C:19]([NH:20][C:27]([NH:38][CH2:36][CH3:37])=[O:33])=[CH:18][CH:17]=1
Reactant: CCN
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: COc1cc2ncnc(Oc3ccc(N)cc3)c2cc1OC
Agent: Cl
Solvent: CO
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Product: CCNC(=O)Nc1ccc(Oc2ncnc3cc(OC)c(OC)cc23)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 16.1 %

Procedure:
4-[(6,7-Dimethoxy-4-quinazolinyl)oxy]aniline (50 mg) was dissolved in chloroform (3 ml) and triethylamine (0.2 ml), and a solution of triphosgene (50 mg) in chloroform was then added to the solution. The mixture was stirred at room temperature for 30 min. Next, ethylamine hydrochloride (69 mg) was added to the reaction solution, and the mixture was further stirred at room temperature overnight. Methanol was added to the reaction solution, and the solution was purified by HPLC by development with chloroform/methanol to give 10 mg (yield 16%) of the title compound.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([Br:9])[C:3]=1[OH:10].[Br:11][CH2:12][CH2:13]Br.[OH-].[K+]>C(O)C>[Br:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([Br:9])[C:3]=1[O:10][CH2:13][CH2:12][Br:11]
Reactant: BrCCBr
Reactant: Cc1cc(Br)c(O)c(Br)c1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: Cc1cc(Br)c(OCCBr)c(Br)c1
Yield: 65.7 %

Procedure:
A mixture of 2,6-dibromo-4-methylphenol (18) (26.59 g, 0.1 mol), 1,2-dibromoethane (11.2 ml, 0.13 mol) and potassium hydroxide (8.42 g, 0.15 mol) in 200 ml of absolute ethanol was heated under reflux for 24 hours. The inorganic salt was collected on a filter and the filtrate taken to dryness The resulting mixture was treated with ethyl ether, chilled, and the solid, which proved to be recovered phenol, collected on a filter. The filtrate was evaporated to afford the ether 19 (24.5 g, 65.7%) as a liquid. This was purified by distillation (0.5 torr, 120°-124° C.) to yield 19.79 g (53.0%) of product. NMR (CDCl3) δ 7.25 (s, 2H, aromatic protons), 3.55-4.38 (m, 4H, 2CH2), and 2.27 (s, 3H, CH3).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:16]=[C:15](Cl)[N:14]=[C:13]([Cl:18])[N:12]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[CH:19]1([CH2:25][NH2:26])[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1.[OH-].[Na+].Cl>CC(C)=O>[Cl:18][C:13]1[N:12]=[C:11]([NH:10][C:4]2[CH:5]=[CH:6][C:7]([O:8][CH3:9])=[C:2]([Cl:1])[CH:3]=2)[N:16]=[C:15]([NH:26][CH2:25][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[N:14]=1
Reactant: NCC1CCCCC1
Reactant: COc1ccc(Nc2nc(Cl)nc(Cl)n2)cc1Cl
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)=O
Product: COc1ccc(Nc2nc(Cl)nc(NCC3CCCCC3)n2)cc1Cl
Yield: 75.9 %

Procedure:
To a sample of 101 (0.3004 g, 1.0 mmol, prepared as indicated herein) dissolved in acetone (4 mL) was added a solution of cyclohexanemethylamine (0.13 mL, 1.0 mmol) in acetone (1 mL) followed by addition of a NaOH solution (0.0448 g, 1.0 mmol dissolved in 1 mL of H2O). The reaction mixture was allowed to stir at reflux for about 3 hours. The reaction mixture was then poured over crushed ice and neutralized with 10% HCl (aq) and 5% NaOH (aq). The resulting solid was collected by vacuum filtration, washed with water and dried overnight under vacuum to afford compound 102 (0.29 g, 76% recovery).
Reaction SMILES: OC(CCCCC)/C=C/[CH:5]1[CH2:7][C:6]1([C:12]([O:14][CH3:15])=O)C(OC)=O.O1CCCCC1OC1CCCCO1.[C:34]([O:37][CH2:38][C@@H:39]1[C:41]([C:47]([O:49][CH2:50][CH3:51])=[O:48])([C:42]([O:44][CH2:45][CH3:46])=[O:43])[C@H:40]1[CH:52]=[CH:53][CH:54]([OH:60])[CH2:55][CH2:56][CH2:57][CH2:58][CH3:59])(=[O:36])[CH3:35]>>[C:34]([O:37][CH2:38][C@@H:39]1[C:41]([C:47]([O:49][CH2:50][CH3:51])=[O:48])([C:42]([O:44][CH2:45][CH3:46])=[O:43])[C@H:40]1[CH:52]=[CH:53][CH:54]([O:60][CH:12]1[CH2:6][CH2:7][CH2:5][CH2:15][O:14]1)[CH2:55][CH2:56][CH2:57][CH2:58][CH3:59])(=[O:36])[CH3:35].[CH3:38][C@@H:39]1[C:41]([C:42]([O:44][CH3:45])=[O:43])([C:47]([O:49][CH3:50])=[O:48])[C@H:40]1[CH:52]=[CH:53][CH:54]([OH:60])[CH2:55][CH:56]=[CH:57][CH3:58]
Reactant: CCCCCC(O)C=C[C@H]1[C@H](COC(C)=O)C1(C(=O)OCC)C(=O)OCC
Reactant: CCCCCC(O)/C=C/C1CC1(C(=O)OC)C(=O)OC
Agent: C1CCC(OC2CCCCO2)OC1
Product: CC=CCC(O)C=C[C@H]1[C@H](C)C1(C(=O)OC)C(=O)OC
Product: CCCCCC(C=C[C@H]1[C@H](COC(C)=O)C1(C(=O)OCC)C(=O)OCC)OC1CCCCO1

Procedure:
In the same manner but using an equivalent amount of one of the compounds of formula of formula II (R5 = H), for example, the compounds listed in Examples 43 to 76, instead of dimethyl trans-2-(3-hydroxy-1-octenyl)cyclopropane-1,1-dicarboxylate, then the corresponding tetrahydropyranyl ether compound of formula II (R5 = tetrahydropyranyl) is obtained, for example, the corresponding tetrahydropyranyl ether compounds of Examples 43 to 76, respectively. More specifically exemplified, in the same manner diethyl trans-3-(acetoxymethyl)-2-(3-hydroxy-1-octenyl)cyclopropane-1,1-dicarboxylate (Example 73) gives diethyl trans-3-(acetoxymethyl)-2-{3-[(tetrahydropyran-2-yl)oxy]-1-octenyl}cyclopropane-1,1-dicarboxylate, γmaxfilm 1740, 1720 cm-1, and dimethyl trans-3-methyl-2-(3-hydroxy-1,5-heptadienyl)cyclopropane-1,1-dicarboxylate (Example 58) gives dimethyl trans-2-{3-[(tetrahydropyran-2-yl)oxy]-1,5-heptadienyl}cyclopropane-1,1-dicarboxylate.