Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([CH2:6][CH:7]([C:18]2[NH:28][C:21]3=[N:22][CH:23]=[C:24]([CH:26]=[O:27])[CH:25]=[C:20]3[CH:19]=2)[C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][CH:9]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[BH4-].[Na+]>CO>[CH:1]1([CH2:6][CH:7]([C:18]2[NH:28][C:21]3=[N:22][CH:23]=[C:24]([CH2:26][OH:27])[CH:25]=[C:20]3[CH:19]=2)[C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][CH:9]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: CS(=O)(=O)c1ccc(C(CC2CCCC2)c2cc3cc(C=O)cnc3[nH]2)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CS(=O)(=O)c1ccc(C(CC2CCCC2)c2cc3cc(CO)cnc3[nH]2)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 82 %

Procedure:
To a stirred solution of 2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-carbaldehyde (104 mg, 0.26 mmol) in dry methanol (5 mL) was added sodium borohydride (40 mg, 1.05 mmol) at 0° C. The resulting mixture was stirred at room temperature for 2 h and then quenched with a saturated ammonium chloride solution, extracted with ethyl acetate and washed with brine, dried over anhydrous sodium sulfate. The solvent was evaporated in vacuo. Purification using a Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) afforded {2-[2-cyclopentyl-1-(4-methanesulfonyl-phenyl)-ethyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-methanol (85 mg, 81%) as a white solid: LC/MS m/e calcd for C22H26N2O3S [M+H]+ 399.53, observed 399.1; 1H NMR (400 MHz, CDCl3) δ ppm 1.18 (m, 2H), 1.48 (m, 2H), 1.56-1.87 (m, 5H, H), 2.13 (m, 1H), 2.24 (m, 1H), 3.04 (s, 3H), 3.59 (br, 1H), 4.30 (t, J=7.7 Hz, 1H), 4.08 (s, 2H), 6.41 (s, 1H), 7.50 (d, J=8.2 Hz, 2H), 7.87 (d, J=8.2 Hz, 2H), 8.02 (s, 1H), 8.14 (br. s., 1H), 10.80 (br, 1H).
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.CN(C)C1(C2C=CC(C)=CC=2)CCC(=O)CC1.CI.[CH2:32]([CH:34]1[CH2:39][C:38]([N:47]([CH3:49])[CH3:48])([C:40]2[CH:45]=[CH:44][C:43]([CH3:46])=[CH:42][CH:41]=2)[CH2:37][CH2:36][C:35]1=[O:50])C>CCCCC.O.C1C=CC=CC=1.C(Cl)(Cl)Cl.CO.O1CCCC1>[CH3:32][CH:34]1[CH2:39][C:38]([N:47]([CH3:48])[CH3:49])([C:40]2[CH:41]=[CH:42][C:43]([CH3:46])=[CH:44][CH:45]=2)[CH2:37][CH2:36][C:35]1=[O:50]
Reactant: CCC1CC(c2ccc(C)cc2)(N(C)C)CCC1=O
Agent: Cc1ccc(C2(N(C)C)CCC(=O)CC2)cc1
Agent: [Li]CCCC
Solvent: CO
Solvent: CC(C)NC(C)C
Solvent: ClC(Cl)Cl
Product: Cc1ccc(C2(N(C)C)CCC(=O)C(C)C2)cc1
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 39 %

Procedure:
A solution consisting of 1.02 gm. (0.010 mole) diisopropylamine in 20 ml. tetrahydrofuran was chilled in an ice:methanol bath before 6 ml. of 1.68 N butyllithium in pentane is added. To this mixture is then added a solution consisting of 2.31 gm. (0.010 mole) of 4-dimethylamino-4-(p-tolyl)cyclohexanone (prepared in Example 14) and 40 ml. tetrahydrofuran. Five minutes later, 2.82 gm. methyl iodide is added, and the mixture is stirred for 45 min. in the cold. It is allowed to warm to 25° C. and stirring is continued for 5 hours, when the reaction mixture is diluted with a mixture of water and benzene. The organic layer is separated and washed first with water and then with brine. The organic solvents are removed by evaporation under reduced pressure, and the residual waxy solid thus obtained is transferred to a column of the grade silica gel 1" by 48". The chromatogram is developed with a solvent medium consisting of 7.5% methanol in chloroform and 20-ml. fractions are collected. The fractions which contain product (as determined by TLC) are combined. The solvent is removed by evaporation under reduced pressure, and the residue thus obtained is recrystallized from diethyl ether. There is thus obtained 1.01 gm. (39% yield) of the object compound 2-ethyl-4-dimethylamino-4-(p-tolyl)cyclohexanone having a melting point at 102° to 104.5° C. NMR suggests assignment of cis relationship of 2-methyl to 4-N(CH3)2.
Reaction SMILES: S(Cl)([Cl:3])=O.[Cl:5][C:6]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][C:7]=1[C:8](O)=[O:9]>C(Cl)(Cl)Cl>[Cl:5][C:6]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][C:7]=1[C:8]([Cl:3])=[O:9]
Reactant: O=C(O)c1cc([N+](=O)[O-])ccc1Cl
Reactant: O=S(Cl)Cl
Solvent: ClC(Cl)Cl
Product: O=C(Cl)c1cc([N+](=O)[O-])ccc1Cl
Temperature: 25 °C
Yield: 91.6 %

Procedure:
Thionyl chloride (14 mL, 192 mmol) was added-dropwise to a solution of 2-chloro-5-nitrobenzoic acid (10 g, 49.6 mmol) in chloroform (150 mL) at 0° C. The mixture was heated to reflux for 4 h then cooled to r.t., concentrated in vacuo and dried under high vacuum to yield 2-chloro-5-nitrobenzoyl chloride (10 g, 91.7%) as a solid. Under nitrogen, triethylamine (19 mL, 136 mmol) was added slowly to a solution of aminoacetaldehyde dimethyl acetal (5.43 mL, 50.0 mmol) in dry DCM (20 mL) at 0° C. 2-Chloro-5-nitrobenzoyl chloride (10 g, 45.5 mmol) was slurried in dry DCM (30 mL) and added over a period of 30 minutes. The mixture was allowed to warm to r.t. and stirred overnight then partitioned between water and DCM. The organic phase was washed with saturated sodium bicarbonate solution, water and brine then dried over sodium sulfate and concentrated. The crude product was triturated with petroleum ether then diethyl ether and finally purified by column chromatography on silica gel (60-120 mesh) eluting with ethyl acetate/petroleum ether (2% to 40% gradient) to afford 2-chloro-N-(2,2-dimethoxy-ethyl)-5-nitro benzamide (8.3 g, 63%) as a yellow solid.
Reaction SMILES: [Cl:1][C:2]1[C:3]([O:16]C)=[CH:4][C:5]([O:14]C)=[C:6]([N:8]=[C:9]2[NH:13][CH2:12][CH2:11][NH:10]2)[CH:7]=1.[BrH:18]>>[BrH:18].[Cl:1][C:2]1[C:3]([OH:16])=[CH:4][C:5]([OH:14])=[C:6]([N:8]=[C:9]2[NH:10][CH2:11][CH2:12][NH:13]2)[CH:7]=1
Reactant: COc1cc(OC)c(N=C2NCCN2)cc1Cl
Agent: Br
Product: Oc1cc(O)c(N=C2NCCN2)cc1Cl
Reaction time: 8 h
Yield: 60.5 %

Procedure:
A mixture of 10 gm of 2-(5-chloro-2,4-dimethoxy-phenylimino)-imidazolidine (0.03 mol) and 150 ml of 48% hydrobromic acid was refluxed for six hours. Thereafter, the clear, homogeneous reaction mixture was allowed to stand overnight in the refrigerator. The crystalline precipitate which had formed was collected by suction filtration, washed with ether and dried, yielding 5.6 gm (60.5% of theory) of 2-(5-chloro-2,4-dihydroxy-phenylimino)-imidazolidine hydrobromide, Rf -value 0.5 in mobile phase 75 parts sec.butanol, 15 parts formic acid, 10 parts water. Carrier: silicagel; visualization: potassium iodoplatinate.
Reaction SMILES: C([Li])CCC.[F:6][C:7]1[CH:30]=[CH:29][C:10]([CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][CH:16]([N:19]3[C:27]4[C:22](=[CH:23][CH:24]=[C:25](Br)[CH:26]=4)[CH2:21][CH2:20]3)[CH2:15][CH2:14]2)=[CH:9][CH:8]=1.CN(C)[CH:33]=[O:34].[Cl-].[NH4+]>CCCCCC.O1CCCC1.C(OCC)(=O)C>[F:6][C:7]1[CH:30]=[CH:29][C:10]([CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][CH:16]([N:19]3[C:27]4[C:22](=[CH:23][CH:24]=[C:25]([CH:33]=[O:34])[CH:26]=4)[CH2:21][CH2:20]3)[CH2:15][CH2:14]2)=[CH:9][CH:8]=1
Reactant: Fc1ccc(CCN2CCC(N3CCc4ccc(Br)cc43)CC2)cc1
Reactant: CN(C)C=O
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCCCCC
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: O=Cc1ccc2c(c1)N(C1CCN(CCc3ccc(F)cc3)CC1)CC2
Reaction time: 0.17 h

Procedure:
A 2.5 M solution (50 ml) of n-butyllithium in hexane was added dropwise at −78° C. into a solution of 1-[1-(4-fluorophenethyl)piperidin-4-yl]-6-bromoindoline (40 g) in tetrahydrofuran (1 l) over 10 min. After 10 min, dimethylformamide (11.6 ml) was added thereto and the resultant mixture was warmed to room temperature. Next, a saturated aqueous solution of ammonium chloride (200 ml) and ethyl acetate (500 ml) were added thereto and the layers were separated. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the crude title compound (37.5 g). A portion of this crude product was purified by silica gel column chromatography (ethyl acetate/ethanol system) to give the title compound as a yellow powder.
Reaction SMILES: Br[C:2]1[C:3]2[N:4]([N:8]=[C:9]([NH2:11])[N:10]=2)[CH:5]=[CH:6][CH:7]=1.[F:12][C:13]([F:24])([F:23])[C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[CH:16][CH:15]=1>>[F:12][C:13]([F:24])([F:23])[C:14]1[CH:19]=[CH:18][C:17]([C:2]2[C:3]3[N:4]([N:8]=[C:9]([NH2:11])[N:10]=3)[CH:5]=[CH:6][CH:7]=2)=[CH:16][CH:15]=1
Reactant: Nc1nc2c(Br)cccn2n1
Reactant: OB(O)c1ccc(C(F)(F)F)cc1
Product: Nc1nc2c(-c3ccc(C(F)(F)F)cc3)cccn2n1

Procedure:
8-(4-Trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine was prepared from 8-bromo-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (504.7 mg, 2.369 mmol) and (4-trifluoromethylphenyl)boronic acid (500.0 mg, 2.632 mmol) in a manner analogous to Step 2c. The reaction product was isolated as a yellow solid (0.64 g, 97%). MP=186-187° C. 1H NMR (400 MHz, (D3C)2SO, δ, ppm): 8.62 (d, J=6.3 Hz, 1H), 8.34 (d, J=8.0 Hz, 2H), 7.88-7.80 (m, 3H), 7.02 (t, J=6.8 Hz, 1H), 6.18 (s, 2H). MS=279 (MH)+. 64b) [4-(4-Methyl-piperazin-1-yl)-phenyl]-[8-(4-trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-yl]-amine was prepared from 8-(4-trifluoromethyl-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (75.0 mg, 0.270 mmol) and 1-(4-bromo-phenyl)-4-methyl-piperazine (80.0 mg, 0.314 mmol) with 2,2′-bis-dicyclohexylphosphanyl-biphenyl (30.0 mg, 0.0549 mmol) as the ligand in a manner analogous to Step 2d. The title compound was isolated as a yellow solid (0.033 g, 27%). MP=214-216° C. 1H NMR (400 MHz, CDCl3, δ, ppm): 8.44 (d, J=6.5 Hz, 1H), 8.12 (dm J=8.7 Hz, 2H), 7.77 (d, J=7.4 Hz, 2H), 7.59 (d, J=7.4 Hz, 1H), 7.49 (d, J=7.6 Hz, 2H), 7.00-6.93 (m, 3H), 6.66 (s, 1H), 3.20-3.15 (m, 4H), 2.62-2.57 (m, 4H), 2.36 (s, 3H). MS=453 (MH)+.
Reaction SMILES: [C:1]([NH:8][C@@H:9]([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C@@H:10]([OH:25])[CH2:11][C@@H:12]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[O:23][CH3:24])[C:13]([OH:15])=[O:14])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].N1C=CN=C1.[C:38]([Si:42]([CH3:45])([CH3:44])Cl)([CH3:41])([CH3:40])[CH3:39]>CN(C=O)C>[C:1]([NH:8][C@@H:9]([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C@@H:10]([O:25][Si:42]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:45])[CH3:44])[CH2:11][C@@H:12]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[O:23][CH3:24])[C:13]([OH:15])=[O:14])([O:3][C:4]([CH3:6])([CH3:7])[CH3:5])=[O:2]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: COc1ccccc1C[C@H](C[C@H](O)[C@H](Cc1ccccc1)NC(=O)OC(C)(C)C)C(=O)O
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: COc1ccccc1C[C@H](C[C@H](O[Si](C)(C)C(C)(C)C)[C@H](Cc1ccccc1)NC(=O)OC(C)(C)C)C(=O)O
Temperature: 25 °C
Reaction time: 20 h

Procedure:
A solution of 500 mg of 5(S)-(Boc-amino)-4(S)-hydroxy-6-phenyl-2(R)-[(2-methoxyphenyl)methyl]hexanoic acid in 5 ml of DMF is treated, while being stirred, with 614 mg of imidazole and 796 mg of tert-butyldimethylchlorosilane. After it has been stirred at RT for 20 h, the reaction solution is poured onto ice-water and the whole is extracted with ethyl acetate. The organic phase is washed with 10% citric acid solution and saline. The silyl ester group in the crude product is detached, at RT in 2 h, in a mixture consisting of 13.29 ml of methanol, 5.13 ml of THF, 5.13 ml of water and 904 mg of potassium carbonate. The mixture is concentrated down to half its volume on a RE at approximately 30° C., and the residue is diluted with ethyl acetate, and the organic phase is washed with 10% citric acid and saline (all being cold). The combined aqueous phases are reextracted with ethyl acetate. The combined organic phases are dried over sodium sulfate and the residue is chromatographed on silica gel (eluent, hexane:ethyl acetate, 3:1 and 1:1), and the title compound is obtained. TLC Rf (hexane/ethyl acetate 2.5:1)=0.12. FAB-MS (M+H)+ =558.
Reaction SMILES: [CH2:1]([C:3]([CH:17]([CH3:24])[CH2:18][CH:19]=[C:20]([CH3:23])[CH2:21][CH3:22])=[CH:4][CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10]([CH2:11][CH2:12][CH2:13][O:14]2)=[CH:9][CH:8]=1)[CH3:2].C(OO)(=[O:27])C>>[O:27]1[C:20]([CH3:23])([CH2:21][CH3:22])[CH:19]1[CH2:18][CH:17]([CH3:24])[C:3]([CH2:1][CH3:2])=[CH:4][CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10]([CH2:11][CH2:12][CH2:13][O:14]2)=[CH:9][CH:8]=1
Reactant: CCC(C)=CCC(C)C(=CCOc1ccc2c(c1)OCCC2)CC
Reactant: CC(=O)OO
Product: CCC(=CCOc1ccc2c(c1)OCCC2)C(C)CC1OC1(C)CC

Procedure:
Following the procedure of Example 17, 7 -(3-ethyl-4,7-dimethyl-2,6-nonadienyloxy)-chromane and peracetic acid are reacted to form 7-(6,7-epoxy-3-ethyl-4,7-dimethyl-2-nonenyloxy)-chromane, nD20 = 1.5190.
Reaction SMILES: [F:1][C:2]1[CH:21]=[CH:20][CH:19]=[CH:18][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][C:11]([CH3:14])=[N:12][CH:13]=[C:8]2[C:7]([C:15](=[NH:17])[NH2:16])=[N:6]1.[C:22]([CH:24]([C:32]#[N:33])[C:25]([CH3:31])([CH3:30])[C:26](OC)=[O:27])#[N:23].CC(C)([O-])C.[K+].O>C(O)(C)(C)C>[NH2:23][C:22]1[C:24]2[C:25]([CH3:31])([CH3:30])[C:26](=[O:27])[NH:33][C:32]=2[N:17]=[C:15]([C:7]2[C:8]3[C:9](=[N:10][C:11]([CH3:14])=[N:12][CH:13]=3)[N:5]([CH2:4][C:3]3[CH:18]=[CH:19][CH:20]=[CH:21][C:2]=3[F:1])[N:6]=2)[N:16]=1
Reactant: COC(=O)C(C)(C)C(C#N)C#N
Reactant: Cc1ncc2c(C(=N)N)nn(Cc3ccccc3F)c2n1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CC(C)(C)O
Solvent: O
Product: Cc1ncc2c(-c3nc(N)c4c(n3)NC(=O)C4(C)C)nn(Cc3ccccc3F)c2n1

Procedure:
200 mg (0.70 mmol) of 1-(2-fluorobenzyl)-6-methyl-1H-pyrazolo[3,4-d]pyrimidine-3-carboximidamide were admixed with 3 ml of tert-butanol, 146 mg (0.70 mmol) of methyl 3,3-dicyano-2,2-dimethylpropanoate dissolved in 1.5 ml of tert-butanol and 94 mg (0.84 mmol) of potassium tert-butoxide, and the mixture was heated under reflux for 48 h. Water was added and the precipitate was filtered off. The filtrate was extracted with dichloromethane, and the organic phase was dried over sodium sulphate and concentrated on a rotary evaporator. The residue was stirred with water/ethanol. The solid was filtered off and dried under high vacuum. 102 mg (34% of theory) of the target compound were obtained.
Reaction SMILES: C([O-])=O.[NH4+].[CH2:5]([O:12][C:13]1[C:18]([O:19][CH3:20])=[CH:17][C:16]([C:21](=[O:23])[CH3:22])=[C:15]([N+:24]([O-])=O)[CH:14]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C1(C)C=CC=CC=1>[Fe].O>[NH2:24][C:15]1[CH:14]=[C:13]([O:12][CH2:5][C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:18]([O:19][CH3:20])=[CH:17][C:16]=1[C:21](=[O:23])[CH3:22]
Reactant: COc1cc(C(C)=O)c([N+](=O)[O-])cc1OCc1ccccc1
Agent: [Fe]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: O
Solvent: Cc1ccccc1
Product: COc1cc(C(C)=O)c(N)cc1OCc1ccccc1
Yield: 90 %

Procedure:
A mixture of iron powder (27 g, 0.48 g atoms), ammonium formate-(31 g, 500 mmol), 1-(4-benzyloxy-5-methoxy-2-nitrophenyl)ethanone (36 g, 120 mmol), toluene (500 mL) and water (500 mL) was heated to reflux overnight. The mixture was filtered through celite and washed with ethyl acetate. The combined organic layers were washed with water and brine. The organic layer was dried over Na2SO4 and concentrated to afford 1-(2-amino-4-benzyloxy-5-methoxyphenyl)ethanone (29.3 g, 90%). 1H NMR (CDCl3): δ 7.41-7.30 (m, 5H), 7.13 (s, 1H, 6.16 (br s, 2H), 6.10 (s, 1H), 5.13 (s, 2H), 3.83 (s, 3H), 2.51 (s, 3H). LC/MS (M+H=272).
Reaction SMILES: C([CH:3]1[C:8]2([CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)[CH:7](C(OC)=O)[C:6](=[O:18])[NH:5][C:4]1=[O:19])#N.[OH-].[Na+].Cl>C(O)C.O>[O:19]=[C:4]1[NH:5][C:6](=[O:18])[CH2:7][C:8]2([CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)[CH2:3]1
Reactant: COC(=O)C1C(=O)NC(=O)C(C#N)C12CCCCC2
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: O=C1CC2(CCCCC2)CC(=O)N1
Temperature: 20 °C
Yield: 68.5 %

Procedure:
10 g of methyl 5-cyano-2,4-dioxo-3-azaspiro[5,5]undecane-1-carboxylate and 5 g of NaOH dissolved in 125 ml of 2:1 ethanol/water are placed in a 250 ml flask equipped with mechanical agitator, thermometer and condenser. The mixture is heated under reflux for 1.5 hours, acidified with 5% HCl to pH 2 and heated under reflux for 3 hours. By cooling to 20° C. a precipitate is formed which is filtered off, washed with water and dried under vacuum. 4.7 g of 2,4-dioxo-3-azaspiro[5,5]undecane are obtained.
Reaction SMILES: [CH2:1]([O:3][CH:4]([O:24][CH2:25][CH3:26])[CH2:5][NH:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH3:2].[CH2:27]([O:34][C:35](ON1C(=O)CCC1=O)=[O:36])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>CC(C)=O>[CH2:27]([O:34][C:35]([N:6]([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)[CH2:5][CH:4]([O:3][CH2:1][CH3:2])[O:24][CH2:25][CH3:26])=[O:36])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: CCOC(CNCCCCCCOCCCCc1ccccc1)OCC
Reactant: O=C(OCc1ccccc1)ON1C(=O)CCC1=O
Solvent: CC(C)=O
Product: CCOC(CN(CCCCCCOCCCCc1ccccc1)C(=O)OCc1ccccc1)OCC
Temperature: 25 °C
Reaction time: 2 h
Yield: 100.2 %

Procedure:
To a solution of 2,39 g (6,55 mmol) N-diethoxyethyl-6-(4-phenylbutoxy)hexylamine in 25 ml acetone is added 1.59 g (7.07 mmol) N-(benzyloxycarbonyloxy)succinimide. After allowing the mixture to stir for 2 hr at room temperature, acetone is removed by evaporation and 30 ml AcOEt are added thereto. The resulting mixture is washed three times with 30 ml H2O. Once separated, the AcoEt phase is dried on anhydrous Na2SO4 and evaporated to dryness, thereby yielding 3.28 g (99%) N-benzyloxycarbonyl-N-diethoxyethyl-6-(phenylbutoxy)hexylamine as an oil.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][N+:5]([O-])=[CH:4][CH:3]=1.C[Si]([C:13]#[N:14])(C)C.CN(C)C(Cl)=O.C([O-])([O-])=O.[K+].[K+]>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:13]#[N:14])[CH:3]=1
Reactant: [O-][n+]1ccc(Cl)cc1
Reactant: C[Si](C)(C)C#N
Agent: CN(C)C(=O)Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Product: N#Cc1cc(Cl)ccn1
Temperature: 0 °C
Reaction time: 16 h
Yield: 100 %

Procedure:
To a mixture of 4-chloropiridine-N-oxide (5.00 g, 38.6 mmol) and trimethylsilyl cyanide (4.84 g, 46.3 mmol) in dichloromethane (60 ml) cooled to 0° C. was added dropwise N,N-dimethylcarbamoyl chloride (3.8 ml, 40.5 mmol). The mixture was allowed to warm to ambient temperature and stirred for 16 h. The mixture was cooled to 0° C. and a 30% aqueous solution of K2CO3 (100 ml) was added. The crude product was extracted with dichloromethane (100 ml×2), the organic extracts dried (MgSO4) and evaporated to give 4-chloro-2-pyridinecarbonitrile (5.35 g, 100%). 1H-NMR (CDCl3) δ: 8.63 (1 H, d, J=4.8 Hz), 7.72 (1 H, d, J=2.6 Hz), 7.55 (1 H, dd, J=1.8, 5.1 Hz).
Reaction SMILES: [C:1]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])(=[O:4])[NH:2][NH2:3].[Cl:10][C:11]([Cl:17])([Cl:16])[C:12](=[NH:15])OC>>[Cl:10][C:11]([Cl:17])([Cl:16])[C:12]([NH:3][NH:2][C:1]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4])=[NH:15]
Reactant: COC(=N)C(Cl)(Cl)Cl
Reactant: CC(C)(C)OC(=O)NN
Product: CC(C)(C)OC(=O)NNC(=N)C(Cl)(Cl)Cl
Temperature: 25 °C
Reaction time: 16 h
Yield: 86 %

Procedure:
A mixture of 2.9 g (0.025 mole) t-butyl carbazate and 10 ml (14.3 g, 0.08 mole) methyl 2,2,2-trichloroacetimidate was stirred 16 hours at room temperature. The solid that was left was washed with petroleum ether and dried to give 6.0 g (86% yield mp 150° C.). The structure was confirmed via infrared and elemental analysis.
Reaction SMILES: [CH2:1]([CH:4]1[CH2:6][C:5]1([C:11]([O-:13])=O)[C:7]([O:9][CH3:10])=[O:8])[CH2:2][CH3:3].ClC(OCC)=O.[Br:20][C:21]1[CH:27]=[CH:26][C:24]([NH2:25])=[C:23]([CH3:28])[CH:22]=1.C(N(CC)CC)C>>[Br:20][C:21]1[CH:27]=[CH:26][C:24]([NH:25][C:11]([C:5]2([C:7]([O:9][CH3:10])=[O:8])[CH2:6][CH:4]2[CH2:1][CH2:2][CH3:3])=[O:13])=[C:23]([CH3:28])[CH:22]=1
Reactant: Cc1cc(Br)ccc1N
Reactant: CCCC1CC1(C(=O)[O-])C(=O)OC
Agent: CCOC(=O)Cl
Solvent: CCN(CC)CC
Product: CCCC1CC1(C(=O)Nc1ccc(Br)cc1C)C(=O)OC
Yield: 53.8 %

Procedure:
Mono-methyl 2-(n-propyl)cyclopropane-1,1-dicarboxylate (2.47 grams, 0.013 mole) from Part B, above, ethyl chloroformate (1.44 grams, 0.013 mole) and 4-bromo-2-methylaniline (2.48 grams, 0.013 mole) were reacted sequentially in the presence of triethylamine (1.35 grams, 0.013 mole) in a manner similar to that described in Example XXXIII to give 2.43 grams (0.007 mole) of methyl 1-(4-bromo-2-methyl-phenylaminocarbonyl)-2-n-propylcyclopropanecarb oxylate having a melting point of 60° C.-≢66° C.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[C:4]([C:10]2[CH:15]=[C:14]([O:16][CH3:17])[C:13]([O:18][CH3:19])=[C:12]([O:20][CH3:21])[CH:11]=2)[O:5][C:6]=1[CH2:7][CH2:8][OH:9].[C:22]1([CH3:32])[CH:27]=[CH:26][C:25]([S:28](Cl)(=[O:30])=[O:29])=[CH:24][CH:23]=1.N1C=CC=CC=1>O>[C:22]1([CH3:32])[CH:27]=[CH:26][C:25]([S:28]([O:9][CH2:8][CH2:7][C:6]2[O:5][C:4]([C:10]3[CH:15]=[C:14]([O:16][CH3:17])[C:13]([O:18][CH3:19])=[C:12]([O:20][CH3:21])[CH:11]=3)=[N:3][C:2]=2[CH3:1])(=[O:30])=[O:29])=[CH:24][CH:23]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: COc1cc(-c2nc(C)c(CCO)o2)cc(OC)c1OC
Solvent: O
Solvent: c1ccncc1
Product: COc1cc(-c2nc(C)c(CCOS(=O)(=O)c3ccc(C)cc3)o2)cc(OC)c1OC
Temperature: 25 °C
Reaction time: 5 h

Procedure:
To the solution of 2-[4-methyl-2-(3,4,5-trimethoxyphenyl)-1,3-oxazol-5-yl]ethanol (2.93 g, 10 mmol) in 30 ml of pyridine 4-toluenesulfonyl chloride (1.9 g, 10 mmol) was added portionwise at room temperature. Subsequently, the reaction mixture was stirred for 5 h at room temperature, and then poured into 200 ml of water and extracted (3×) with 50 ml of dichloromethane. The combined extracts were washed with 1M HCl, an aqueous solution of sodium bicarbonate, and brine. The organic phase was dried over magnesium sulfate and the solvent was evaporated, to obtain a product, 2-[4-methyl-2-(3,4,5-trimethoxyphenyl)-1,3-oxazol-5-yl]ethyl 4-toluenesulfonate having the purity of ca. 95%.
Reaction SMILES: Br[C:2]1[C:3]2[S:17][CH:16]=[CH:15][C:4]=2[N:5]=[C:6]([C:8]2[CH:9]=[C:10]([OH:14])[CH:11]=[CH:12][CH:13]=2)[N:7]=1.C([Sn](CCCC)(CCCC)[C:23]1[S:27][CH:26]=[N:25][CH:24]=1)CCC>CC(N(C)C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[S:27]1[C:23]([C:2]2[C:3]3[S:17][CH:16]=[CH:15][C:4]=3[N:5]=[C:6]([C:8]3[CH:9]=[C:10]([OH:14])[CH:11]=[CH:12][CH:13]=3)[N:7]=2)=[CH:24][N:25]=[CH:26]1
Reactant: Oc1cccc(-c2nc(Br)c3sccc3n2)c1
Reactant: CCCC[Sn](CCCC)(CCCC)c1cncs1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CC(=O)N(C)C
Product: Oc1cccc(-c2nc(-c3cncs3)c3sccc3n2)c1
Temperature: 150 °C
Yield: 14.4 %

Procedure:
A suspension of 3-(4-bromo-thieno[3,2-d]pyrimidin-2-yl)-phenol (150 mg, 0.49 mmol), 5-tributylstannanyl-thiazole (275 mg, 0.735 mmol), and Pd(PPh3)4 (28 mg, 0.0245 mmol) in anhydrous DMA (4 ml) was heated in a microwave at 150° C. for 15 mins. The reaction was extracted into ethyl acetate, washing with brine and water before drying the organic layer over MgSO4. The crude material was purified by flash column chromatography using 1:1 ethyl acetate/petrol as the eluent. The resulting solid was triturated with dichloromethane to give the title compound as an off-white solid (22 mg, 14%).
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH:6](O)/[CH:7]=[CH:8]/[CH:9]=[CH:10]\[CH2:11]/[CH:12]=[CH:13]\[CH2:14]/[CH:15]=[CH:16]\[CH2:17][CH2:18][CH2:19][C:20]([OH:22])=[O:21].C(O)(=O)CC(CC(O)=O)(C(O)=O)[OH:27]>>[CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][CH:6]=[CH:7][CH2:8][CH:9]([OH:27])[CH:10]=[CH:11][CH:12]=[CH:13][CH2:14][CH:15]=[CH:16][CH2:17][CH2:18][CH2:19][C:20]([OH:22])=[O:21]
Reactant: O=C(O)CC(O)(CC(=O)O)C(=O)O
Reactant: CCCCCC(O)/C=C/C=C\C/C=C\C/C=C\CCCC(=O)O
Product: CCCCCC=CCC(O)C=CC=CCC=CCCCC(=O)O

Procedure:
Unlabeled 15-HETE and (3H)-12-HETE are added to the citric acid quenched samples as internal standards. After chromatography of the extracted products on silica gel, (14C)-12-HETE is located by the UV absorbence of the added 15-HETE (with which it cochromatographs) and is quantitated by scintillation spectroscopy.