1,1'-Carbonyldiimidazole → N-[(3-Chloropyrazin-2-yl)(2-phenyl-quinolin-7-yl)-methyl]-4-methoxycyclohexanecarboxamide

HRID 386200

반응식

HRID 386200 반응식
[C:1]([N:8]1[CH:12]=[CH:11][N:10]=[CH:9]1)(N1C=CN=C1)=O.[CH3:13][O:14][CH:15]1[CH2:20][CH2:19][CH:18]([C:21]([OH:23])=O)[CH2:17][CH2:16]1.[ClH:24].ClC1C([NH:32][CH2:33][C:34]2[CH:43]=[C:42]3[C:37]([CH:38]=[CH:39][C:40]([C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=4)=[N:41]3)=[CH:36][CH:35]=2)=NC=CN=1>CCOC(C)=O>[Cl:24][C:9]1[C:1]([CH:33]([C:34]2[CH:43]=[C:42]3[C:37]([CH:38]=[CH:39][C:40]([C:44]4[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=4)=[N:41]3)=[CH:36][CH:35]=2)[NH:32][C:21]([CH:18]2[CH2:17][CH2:16][CH:15]([O:14][CH3:13])[CH2:20][CH2:19]2)=[O:23])=[N:8][CH:12]=[CH:11][N:10]=1

참가 물질

5

반응물 3

HCID 682631,1'-CarbonyldiimidazoleHCID 736153Rac-(1r,4r)-4-methoxycyclohexane-1-carboxylic acidHCID 53629041(3-Chloropyrazin-2-yl)(2-phenylquinolin-7-yl)methylamine hydrochloride salt

생성물 1

HCID 53629043N-[(3-Chloropyrazin-2-yl)(2-phenyl-quinolin-7-yl)-methyl]-4-methoxycyclohexanecarboxamide

시약·촉매·용매 1

HCID 8857Ethyl Acetate용매

실험 절차

A round bottom flask, charged with carbonyldiimidazole (252.2 mg, 1.55 mmol) and 4-methoxy-cyclohexanecarboxylic acid (mixture of cis/trans isomers) (242.9 mg, 1.54 mmol) was evacuated and filled with nitrogen. THF (15 mL) was added and the reaction mixture was stirred at 60° C. for 16 h. (3-Chloropyrazin-2-yl)(2-phenylquinolin-7-yl)methylamine hydrochloride salt (500 mg, 1.10 mmol) was then added and stirring was continued at 60° C. for another 20 h. After cooled to rt, the reaction mixture was diluted with 20 mL of EtOAc and washed with sat. NaHCO3 (3×30 mL) followed by brine (3×30 mL). The organic phase was dried over Na2SO4, filtered, concentrated under reduced pressure, and purified by silica gel chromatography (60% EtOAc in hexane 100% EtOAc). N-[(3-Chloropyrazin-2-yl)(2-phenyl-quinolin-7-yl)-methyl]-4-methoxycyclohexanecarboxamide was obtained as a yellow solid. To a solution of N-[(3-chloropyrazin-2-yl)(2-phenyl-quinolin-7-yl)-methyl]-4-methoxycyclohexanecarboxamide (440 mg, 0.91 mmol) in acetonitrile (20 mL) was added POCl3 (0.17 mL, 1.69 mmol) and DMF (0.3 mL). This mixture was heated to 55° C. under N2 for 2 h, concentrated under reduced pressure, and quenched with 2N NH3 in 2-propanol to pH 9. 2-Propanol was removed under reduced pressure and the residue was dissolved in dichloromethane (50 mL) and water (30 mL). Layers were separated and the organic phase was washed with brine and dried over Na2SO4, filtered, concentrated under reduced pressure, and purified by silica gel chromatography (2%→6% CH3CN in dichloromethane) to afford the individual cis-isomer and trans-isomers:

후처리

  1. customwas evacuated
  2. additionfilled with nitrogen
  3. additionTHF (15 mL) was added
  4. additionwas then added
  5. washwashed with sat. NaHCO3 (3×30 mL)
  6. dry with materialThe organic phase was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. custompurified by silica gel chromatography (60% EtOAc in hexane 100% EtOAc)

출처 및 근거

ORD 기록
ord-7edd5d145a2846f38d0e29a8f42c0e48
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08367826B2

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