Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[N:3]([CH2:15][CH2:16][CH2:17][C:18]2([CH3:23])[O:22][CH2:21][CH2:20][O:19]2)[C:4]2[C:13]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[N:7]=[CH:6][C:5]=2[N:14]=1.C1C=C(Cl)C=C(C(OO)=[O:32])C=1>>[CH3:1][C:2]1[N:3]([CH2:15][CH2:16][CH2:17][C:18]2([CH3:23])[O:22][CH2:21][CH2:20][O:19]2)[C:4]2[C:13]3[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=3[N+:7]([O-:32])=[CH:6][C:5]=2[N:14]=1
Reactant: Cc1nc2cnc3ccccc3c2n1CCCC1(C)OCCO1
Reactant: O=C(OO)c1cccc(Cl)c1
Product: Cc1nc2c[n+]([O-])c3ccccc3c2n1CCCC1(C)OCCO1

Procedure:
The general method described in Steps 9 and 10 of Example 1 was used to aminate 2-methyl-1-[3-(2-methyl-[1,3]dioxolan-2-yl)propyl]-1H-imidazo[4,5-c]quinoline (6.70 g, 21.5 mmol) by reaction with m-CPBA (9.4 g) to provide 2-methyl-1-[3-(2-methyl-[1,3]dioxolan-2-yl)-propyl]-5-oxido-1H-imidazo[4,5-c]quinoline followed by reaction with p-toluenesulfonyl chloride (7.20 g, 37.8 mmol) and ammonium hydroxide solution (100 mL) to provide 2-methyl-1-[3-(2-methyl-[1,3]dioxolan-2-yl)propyl]-1H-imidazo[4,5-c]quinolin-4-amine (3.9 g) as an off-white solid after recrystallization from toluene, mp 193-195° C.
Reaction SMILES: [CH:1]([S:4]([CH3:7])(=[O:6])=[O:5])([CH3:3])[CH3:2].CO.C[O-].[Na+].[C:13]([O:18][CH3:19])(=[O:17])[C:14]([O-])=[O:15].Cl>C1COCC1>[CH:1]([S:4]([CH2:7][C:14](=[O:15])[C:13]([O:18][CH3:19])=[O:17])(=[O:6])=[O:5])([CH3:3])[CH3:2]
Reactant: CC(C)S(C)(=O)=O
Reactant: COC(=O)C(=O)[O-]
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: COC(=O)C(=O)CS(=O)(=O)C(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 30.7 %

Procedure:
To a mixture of i-propylmethylsulfone (5.17 g, 42.3 mmol) and THF (20 mL) was added 28% sodium methoxide methanol solution (8.58 g, 44.5 mmol) at room temperature, and then methyl oxalate (5.0 g, 42.3 mmol) was gradually added to the mixture at room temperature. The resulting mixture was stirred at room temperature overnight. To the reaction mixture was added ice-water (200 mL), and the pH of the resulting mixture was adjusted pH3 or less than pH3 with 2 mol/L hydrochloric acid. The mixture was extracted with ethyl acetate (200 mL). The extract was washed with brine (200 mL), dried over anhydrous sodium sulphate, and concentrated in vacuo. The resulting residue was purified on a silica gel column chromatography (ethyl acetate/n-hexane) to give methyl 3-(i-propylsulfonyl)-2-oxopropanoate (2.7 g, yield: 28%) as colorless oil.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([NH:10][C:11]([NH:13][C@@H:14]2[CH2:19][CH2:18][NH:17][CH2:16][C@@H:15]2[CH2:20][N:21]2[CH2:26][CH2:25][CH2:24][C@@H:23]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)[CH2:22]2)=[O:12])[CH:7]=[CH:8][CH:9]=1)(=[O:3])[CH3:2].C(N(CC)CC)C.[C:42](Cl)(=[O:47])[C:43]([CH3:46])([CH3:45])[CH3:44]>ClCCl>[C:1]([C:4]1[CH:5]=[C:6]([NH:10][C:11]([NH:13][C@@H:14]2[CH2:19][CH2:18][N:17]([C:42](=[O:47])[C:43]([CH3:46])([CH3:45])[CH3:44])[CH2:16][C@H:15]2[CH2:20][N:21]2[CH2:26][CH2:25][CH2:24][C@@H:23]([CH2:27][C:28]3[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=3)[CH2:22]2)=[O:12])[CH:7]=[CH:8][CH:9]=1)(=[O:3])[CH3:2]
Reactant: CC(C)(C)C(=O)Cl
Reactant: CC(=O)c1cccc(NC(=O)N[C@@H]2CCNC[C@@H]2CN2CCC[C@@H](Cc3ccc(F)cc3)C2)c1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)c1cccc(NC(=O)N[C@@H]2CCN(C(=O)C(C)(C)C)C[C@H]2CN2CCC[C@@H](Cc3ccc(F)cc3)C2)c1
Reaction time: 17 h
Yield: 46.7 %

Procedure:
In a dry flask 1-(3-acetyl-phenyl)-3-{(3R,4R)-3-[(S)-3-(4-fluoro-benzyl)-piperidin-1-ylmethyl]-piperidin-4-yl}-urea (43 mg, 0.07 mmol) was dissolved in dichloromethane (2 mL), and then triethylamine (65 μL, 0.47 mmol) and pivaloyl chloride (12 μL, 0.10 mmol) were added. The reaction mixture was stirred for 17 hours. The reaction mixture was concentrated in vacuo then was purified by preparative reverse-phase HPLC (10-80% acetonitrile in water with 0.05% trifluoroacetic acid) to give a white amorphous solid (18 mg, 38%). 1H NMR (300 MHz, CD3OD), δ: 8.04 (s, 1H), 7.64 (d, 1H, J=7), 7.58 (dd, 1H, J=7, J′=1), 7.40 (t, 1H, J=8), 7.19 (m, 2H), 6.99 (t, 2H, J=9), 4.27 (d, 1H, J=14), 4.14 (d, 1H, J=15), 3.71 (m, 1H), 3.48 (bm, 3H), 3.25 (m, 2H), 3.07 (m, 1H), 2.95 (m, 2H), 2.66 (m, 2H), 2.57 (s, 3H), 1.98 (m, 4H), 1.76 (m, 2H), 1.62 (m, 1H), 1.28 (s, 9H), 1.20 (m, 1H). HRMS (ESI), C32H44FN4O3 m+/z: calc. 551.3397, found=551.3402.
Reaction SMILES: [CH3:1][NH:2][S:3]([CH2:6][C:7]1[CH:19]=[CH:18][C:10]([NH:11][C:12](=[O:17])[C:13]([F:16])([F:15])[F:14])=[CH:9][CH:8]=1)(=[O:5])=[O:4].C(=O)(O)[O-].[Na+].[Br:25]Br>CO.C(Cl)Cl>[Br:25][C:9]1[CH:8]=[C:7]([CH2:6][S:3]([NH:2][CH3:1])(=[O:5])=[O:4])[CH:19]=[CH:18][C:10]=1[NH:11][C:12](=[O:17])[C:13]([F:16])([F:15])[F:14]
Reactant: BrBr
Reactant: CNS(=O)(=O)Cc1ccc(NC(=O)C(F)(F)F)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CO
Product: CNS(=O)(=O)Cc1ccc(NC(=O)C(F)(F)F)c(Br)c1
Yield: 29.7 %

Procedure:
To a chilled suspension of 4-methylaminosulfonylmethyl-N-trifluoroacetylaniline (10.9 g) in methanol (100 mL) was added sodium bicarbonate (28 g), followed by bromine (18.3 g) in methylene chloride (30 mL). The reaction mixture was then diluted with methylene chloride (70 mL) and quenched by the addition of sodium sulfite (20 g), filtered through CELITE and concentrated in vacuo to a yellow residual solid. This solid was twice reslurried in methylene chloride (300 mL) then refiltered and the filtrates evaporated in vacuo. The residual materials were combined in 10% acetone/methylene chloride solution and concentrated then purified by column chromatography (eluting with 4% acetone in methylene chloride) to give the title compound (4.10 g) mp 170° C.; TLC (methylene chloride/acetone 15:1) Rf=0.36, and the corresponding dibromide (5.56 g) TLC (methylene chloride/acetone 15:1) Rf=0.31.
Reaction SMILES: [F:1][C:2]1[C:11]([F:12])=[C:10]2[C:5]([CH2:6][CH2:7][CH:8]([CH2:13][CH2:14][CH3:15])[O:9]2)=[C:4]2[CH:16]=[C:17]([CH3:19])[O:18][C:3]=12>C1COCC1.[Pd]>[F:1][C:2]1[C:11]([F:12])=[C:10]2[C:5]([CH2:6][CH2:7][CH:8]([CH2:13][CH2:14][CH3:15])[O:9]2)=[C:4]2[CH2:16][CH:17]([CH3:19])[O:18][C:3]=12
Reactant: CCCC1CCc2c(c(F)c(F)c3oc(C)cc23)O1
Agent: [Pd]
Solvent: C1CCOC1
Product: CCCC1CCc2c3c(c(F)c(F)c2O1)OC(C)C3

Procedure:
2.0 g (7.51 mmol) of 4,5-difluoro-2-methyl-7-propyl-8,9-dihydro-7H-furo-[3,2-f]chromene are hydrogenated for 18 h at elevated temperature in THF using elemental hydrogen in the presence of Pd/C (5% Pd). The reaction soln. is concentrated to dryness, and the residue is purified by column chromatography (SiO2, 1-chlorobutane), giving 4,5-difluoro-2-methyl-7-propyl-1,7,8,9-tetrahydro-2H-furo[3,2-f]chromene as a colourless solid having an m.p. of 87° C. (Δ∈=−10.1).
Reaction SMILES: [C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[O:11][C:12]1[CH:17]=[CH:16][C:15](Br)=[C:14]([O:19]C)[CH:13]=1>>[C:1]1([C:15]2[CH:16]=[CH:17][C:12]([OH:11])=[CH:13][C:14]=2[OH:19])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: OB(O)c1ccccc1
Reactant: COc1ccc(Br)c(OC)c1
Product: Oc1ccc(-c2ccccc2)c(O)c1

Procedure:
This compound was prepared using essentially the same procedure as that used in Example 3 with the difference that phenylboronic acid 17 (Aldrich Chemical) was used in place of 2-napthylboronic acid 13, and 1,3-dimethoxy-4-bromobenzene 15 was used in place of 1,3-dimethoxy-4-bromo-2-fluorobenzene 12.
Reaction SMILES: [CH3:1][C:2]([OH:16])([CH2:5][CH2:6][CH:7]=[C:8]([CH3:15])[CH2:9][CH2:10][CH:11]=[C:12]([CH3:14])[CH3:13])[C:3]#[CH:4].[Cl-].[NH4+].[OH2:19].O=O>C(O)C>[CH3:14][C:12](=[CH:11][CH2:10][CH2:9][C:8]([CH3:15])=[CH:7][CH2:6][CH2:5][C:2]([CH3:1])([OH:19])[C:3]#[C:4][C:4]#[C:3][C:2]([CH3:1])([OH:16])[CH2:5][CH2:6][CH:7]=[C:8]([CH3:15])[CH2:9][CH2:10][CH:11]=[C:12]([CH3:14])[CH3:13])[CH3:13]
Reactant: O
Reactant: C#CC(C)(O)CCC=C(C)CCC=C(C)C
Agent: O=O
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Product: CC(C)=CCCC(C)=CCCC(C)(O)C#CC#CC(C)(O)CCC=C(C)CCC=C(C)C

Procedure:
In a 5-l three-necked and round-bottomed flask were placed 114.7 g of 3,7,11-trimethyldodeca-6,10-dien-l-yn- 3-ol, 305.9 g of ammonium chloride, 191.2 g of cuprous chloride, 765 ml of water and 765 ml of ethyl alcohol and the mixture was stirred at room temperature for 18 hours by passing oxygen thereinto. After completion of the reaction there remained no unreacted starting material. The reaction mixture was centrifuged and the mother liquid was extracted with benzene. The benzene and ethyl alcohol were distilled off the organic layer and the residue was dissolved in benzene and washed with water. The benzene layer was dried over anhydrous calcium sulfate and the solid material was filtered off. The benzene was distilled off the benzene layer to give 107.8 g of crude 2,6,10,15,19,23-hexamethyltetracosa-2,6,18,22-tetraene-11,13-diyne-10,15-diol. A 107.8 g of the above diol, 50 ml of ethyl alcohol and 2.5 g of 5 % Pd on active carbon were placed in an autoclave and the mixture was hydrogenated at 100° C under a hydrogen pressure of 3 - 5 kg/cm2 until the absorption of hydrogen stopped. The obtained product consisted of a composition of the compounds (V), (VI) and squalane in the ratio of 84.9 : 14.6 : 0.5 % respectively. The catalyst of Pd/C was filtered off and washed with 450 ml of ethyl alcohol. 14 ml of sulfuric acid was added to the combined ethylalcohol solution consisting of about 500 ml. The mixture was subjected to dehydration at 100° C for 2 hours. After cooling 300 ml of water was added to the reaction mixture and the ethyl alcohol was distilled off and the residue was extracted with benzene. The benzene layer was washed with water and dried over anhydrous sodium sulfate. 2.5 g of 5 % palladium on active carbon was added to the solution and the mixture was subjected to hydrogenation at 50° C under a hydrogen pressure of 3 ~ 5 kg/cm2. After the hydrogenation absorption stopped, the reaction mixture was cooled and the catalyst of Pd/C was filtered off and the benzene was distilled off to afford 78.8 g of a crude squalane. This crude squalane was distilled under reduced pressure to give 68.9 g of purified squalane having the boiling point range of 190° ~ 195°C/0.5 mmHg.
Reaction SMILES: CC1(C)[O:37][C@H:5]2[O:6][CH:7]([CH2:15][O:16][C:17]([N:19]3[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)/[C:21](=[CH:28]/[C:29]4[NH:30][C:31]([CH3:35])=[CH:32][C:33]=4[CH3:34])/[C:20]3=[O:36])=[O:18])[C@@H:8]3[O:12]C(C)(C)[O:10][C@@H:9]3[C@H:4]2[O:3]1>Cl.C1COCC1>[OH:12][C@@H:8]1[C@H:9]([OH:10])[C@@H:4]([OH:3])[CH:5]([OH:37])[O:6][CH:7]1[CH2:15][O:16][C:17]([N:19]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)/[C:21](=[CH:28]/[C:29]2[NH:30][C:31]([CH3:35])=[CH:32][C:33]=2[CH3:34])/[C:20]1=[O:36])=[O:18]
Reactant: Cc1cc(C)c(/C=C2\C(=O)N(C(=O)OCC3O[C@@H]4OC(C)(C)O[C@@H]4[C@H]4OC(C)(C)O[C@@H]34)c3ccccc32)[nH]1
Agent: Cl
Solvent: C1CCOC1
Product: Cc1cc(C)c(/C=C2\C(=O)N(C(=O)OCC3OC(O)[C@H](O)[C@@H](O)[C@H]3O)c3ccccc32)[nH]1
Yield: 60 %

Procedure:
3-[1-(3,5-Dimethyl-1H-pyrrol-2-yl)-meth-(Z)-ylidene]-2-oxo-2,3-dihydro-indole-1-carboxylic acid (3aR, 5aS, 8aS, 8bR)-2,2,7,7-tetramethyl-tetrahydro-bis[1,3]dioxolo[4,5-b;4′,5′-d]pyran-5-ylmethyl ester was dissolved in the mixture of 5.0 mL of 6 N HCl aq. and 20 mL of THF. The resultant mixture was stirred at room temperature for 3 h and 40° C. for 1 h and concentrated. The residue was washed with ethyl acetate and THF and dried to give 133 mg (60%) of 3-[1-(3,5-dimethyl-1H-pyrrol-2-yl)-meth-(Z)-ylidene]-2-oxo-2,3-dihydro-indole-1-carboxylic acid (3R, 4S, 5R)-3,4,5,6-tetrahydroxy-tetrahydro-pyran-2-ylmethyl ester as a yellow solid.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][OH:14])[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].F[C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=1[N+:25]([O-:27])=[O:26].Cl>CN(C)C=O>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][O:14][C:18]1[CH:23]=[CH:22][C:21]([F:24])=[CH:20][C:19]=1[N+:25]([O-:27])=[O:26])[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N[C@@H](CO)C(=O)O
Reactant: O=[N+]([O-])c1cc(F)ccc1F
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N[C@@H](COc1ccc(F)cc1[N+](=O)[O-])C(=O)O
Reaction time: 1 h
Yield: 51.8 %

Procedure:
5.00 g (24.4 mmol) (S)-2-tert-Butoxycarbonylamino-3-hydroxy-propionic acid in 5 ml dimethylformamide were added to a suspension of 2.25 g (51.7 mmol) sodium hydride (55%) in 5 ml dimethylformamide at 0° C. The suspension was stirred for 1 hour and then 4.5 ml (26.8 mmol) 2,5-difluoro-nitrobenzene was added. After additional 3 hours of stirring at 0° C. the mixture was poured on ice/water. The ph was adjusted to 1 by adding 7 ml 25% aqueous hydrochloric acid. Extraction with ethylacetate and chromatography on silicagel with ethylacetate/heptane 1:1 yielded 4.35 g (52%) (S)-2-tert-butoxycarbonylamino-3-(4-fluoro-2-nitro-phenoxy)-propionic acid as yellow solid, MS m/e (%): 343.0 (M−H+, 100).
Reaction SMILES: [Cl:1][C:2]1[C:7](I)=[CH:6][C:5]([N:9]2[C:13](=[O:14])[N:12]([CH:15]([F:17])[F:16])[C:11]([CH3:18])=[N:10]2)=[C:4]([F:19])[CH:3]=1.[OH:20][CH:21]([CH3:29])[C:22](=[CH2:28])[C:23]([O:25][CH2:26][CH3:27])=[O:24].C(N(CCCC)CCCC)CCC>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:21]([CH:22]([CH2:28][C:7]1[CH:6]=[C:5]([N:9]2[C:13](=[O:14])[N:12]([CH:15]([F:17])[F:16])[C:11]([CH3:18])=[N:10]2)[C:4]([F:19])=[CH:3][C:2]=1[Cl:1])[C:23]([O:25][CH2:26][CH3:27])=[O:24])(=[O:20])[CH3:29]
Reactant: C=C(C(=O)OCC)C(C)O
Reactant: Cc1nn(-c2cc(I)c(Cl)cc2F)c(=O)n1C(F)F
Agent: [Pd+2]
Agent: CC(=O)[O-]
Solvent: CCCCN(CCCC)CCCC
Product: CCOC(=O)C(Cc1cc(-n2nc(C)n(C(F)F)c2=O)c(F)cc1Cl)C(C)=O
Yield: 111 %

Procedure:
This compound was prepared in the manner of Example 6, with 18.28 grams (0.0415 mole—1.0 equiv.) of 1-(4-chloro-2-fluoro-5-iodophenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazole, 6.28 grams (0.0436 mole—1.05 equiv.) of ethyl 3-hydroxy-2-methylenebutanoate, 15.4 grams (0.083 mole—2.0 equiv.) of tributylamine, and 0.233 gram (0.0010 mole—0.025 equiv.) of palladium(II) acetate as reagents. A yield of 20.3 grams of 75.6% pure ethyl α-acetyl-2-chloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1yl]4-fluorobenzenepropanoate (87.9% yield) was obtained.
Reaction SMILES: [N+:1]([C:4]1[C:5]([CH3:21])=[C:6]2[C:11](=[C:12]([CH3:15])[C:13]=1[CH3:14])[O:10][C:9]([CH2:17][O:18][CH3:19])([CH3:16])[CH2:8][C:7]2=[O:20])([O-:3])=[O:2].CO.[BH4-].[Na+]>O>[N+:1]([C:4]1[C:5]([CH3:21])=[C:6]2[C:11](=[C:12]([CH3:15])[C:13]=1[CH3:14])[O:10][C:9]([CH2:17][O:18][CH3:19])([CH3:16])[CH2:8][CH:7]2[OH:20])([O-:3])=[O:2]
Reactant: COCC1(C)CC(=O)c2c(C)c([N+](=O)[O-])c(C)c(C)c2O1
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: COCC1(C)CC(O)c2c(C)c([N+](=O)[O-])c(C)c(C)c2O1
Temperature: 0 °C
Reaction time: 1 h
Yield: 100.3 %

Procedure:
To 10 g of 6-nitro-2-methoxymethyl-2,5,7,8-tetramethylchroman-4-one, 100 ml of methanol was added and 1.3 g of sodium borohydride was added at 0° C., followed by stirring at 0° C. for one hour. The reaction solution was poured into water and then extracted with ethyl acetate. The organic layer was washed with saturated saline and then dried over anhydrous magnesium sulfate. After removing magnesium sulfate by filtration and concentrating under reduced pressure, 10.1 g of the objective compound was obtained.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][CH2:5][NH2:6].[Cl:7][CH2:8][CH2:9][N:10]=[C:11]=[O:12]>C1COCC1>[Cl:7][CH2:8][CH2:9][NH:10][C:11]([NH:6][CH2:5][CH2:4][CH2:3][O:2][CH3:1])=[O:12]
Reactant: COCCCN
Reactant: O=C=NCCCl
Solvent: C1CCOC1
Product: COCCCNC(=O)NCCCl
Temperature: 25 °C
Reaction time: 3 h
Yield: 100 %

Procedure:
A solution of 3-methoxypropylamine (0.45 mL, 4.39 mmol) in THF (15 mL) was treated with 2-chloroethylisocyanate (0.35 mL, 4.10 mmol), stirred at RT for 3 h and concentrated to dryness to afford 1-(2-chloroethyl)-3-(3-methoxypropyl)urea (100% yield assumed) as a white solid. MS (ESI) m/z: 195.1 (M+H+).
Reaction SMILES: [CH2:1]([C@@H:8]1[NH:13][CH2:12][CH2:11][N:10]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[CH:15]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O:30][C:31](=O)[CH2:32][C:33]1[NH:37][CH:36]=[N:35][N:34]=1)C>>[CH2:1]([C@H:8]1[CH2:9][N:10]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[CH:15]=2)[CH2:11][CH2:12][N:13]1[C:31](=[O:30])[CH2:32][C:33]1[NH:37][CH:36]=[N:35][N:34]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COc1ccc(N2CCN[C@@H](Cc3ccccc3)C2)cc1OC1CCCC1
Reactant: CCOC(=O)Cc1nnc[nH]1
Product: COc1ccc(N2CCN(C(=O)Cc3nnc[nH]3)[C@@H](Cc3ccccc3)C2)cc1OC1CCCC1
Yield: 20 %

Procedure:
Prepared using the same procedure described in Example 275 with (S)-3-benzyl-1-(3-cyclopentyloxy-4-methoxy-phenyl)-piperazine and (4H-[1,2,4]triazol-3-yl)-acetic acid ethyl ester as starting material. The product was obtained as an off-white solid (105 mg, 20%). LC/MS (Method B) 3.39 min, [M+1]+ 476.
Reaction SMILES: [Mg].[CH2:2](Cl)[C:3]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)([CH3:5])[CH3:4].II.BrCCBr.[C:19](=[O:21])=[O:20]>O1CCCC1>[CH3:4][C:3]([CH3:5])([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH2:2][C:19]([OH:21])=[O:20]
Reactant: CC(C)(CCl)c1ccccc1
Reactant: O=C=O
Agent: II
Agent: [Mg]
Solvent: BrCCBr
Solvent: C1CCOC1
Product: CC(C)(CC(=O)O)c1ccccc1
Reaction time: 5 h
Yield: 81 %

Procedure:
Following a literature procedure, (Leffler, J. E.; Barbas, J. T. JACS. 1981, 103(26), 7768-7773), to a mixture of magnesium turnings (9.5 g) and neophyl chloride (7.5 mL) in tetrahydrofuran (100 mL) is added a spatula tip of iodine and 1,2-dibromoethane (1 mL). The mixture is heated gently with under a heat gun to initiate a vigorous reaction. A solution of neophyl chloride (57 mL) in tetrahydrofuran (360 mL) is added dropwise over the course of 90 minutes. Following completion of the addition, the reaction mixture is stirred for an additional five hours, then solid carbon dioxide (25 g) is added to the flask. After 10 minutes, the flask is transferred to a 40° C. water bath until all carbon dioxide had sublimed. The solvent is then removed under reduced pressure to afford the title compound (58 g, 81%) as a white paste. MS (ES+): (M+H)=178.8