Potassium Carbonate → 2-{5-[6-(4-{2-[1-(2-Methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1751443노트

반응식

HRID 1751443 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:14][C:15]([C:18]2[CH:27]=[CH:26][C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:28]4[CH:33]=[CH:32][C:31]([C:34]5[NH:35][C:36]([CH:39]6[CH2:43][CH2:42][CH2:41][N:40]6[C:44](=[O:57])[CH:45]([NH:52][C:53]([O:55][CH3:56])=[O:54])[CH:46]6[CH2:51][CH2:50]O[CH2:48][CH2:47]6)=[N:37][CH:38]=5)=[CH:30][CH:29]=4)[CH:24]=3)[CH:19]=2)=[CH:16][N:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:58](=O)([O-])[O-].[K+].[K+].COC(NC(C1C=CC=CC=1)C(O)=O)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].CCOC(C(C#N)=NOC(N1CCOCC1)=[N+](C)C)=O.F[P-](F)(F)(F)(F)F>CCO.[Pd].C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:14][C:15]([C:18]2[CH:27]=[CH:26][C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:28]4[CH:29]=[CH:30][C:31]([C:34]5[NH:35][C:36]([CH:39]6[CH2:43][CH2:42][CH2:41][N:40]6[C:44](=[O:57])[CH:45]([NH:52][C:53]([O:55][CH3:56])=[O:54])[C:46]6[CH:51]=[CH:50][CH:58]=[CH:48][CH:47]=6)=[N:37][CH:38]=5)=[CH:32][CH:33]=4)[CH:24]=3)[CH:19]=2)=[CH:16][N:17]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

참가 물질

9

반응물 5

HCID 11430Potassium CarbonateHCID 62657Potassium Phosphate, TribasicHCID 596264N-Methoxycarbonyl-2-phenylglycineHCID 696752322-(5-{6-[4-(2-{1-[2-Methoxycarbonylamino-2-(tetrahydro-pyran-4-yl)-acetyl]-pyrrolidin-2-yl}-3H-imidazol-4-yl)-phenyl]-naphthalen-2-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 75951468(1-Cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate

생성물 1

HCID 696730252-{5-[6-(4-{2-[1-(2-Methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester수율 74%

시약·촉매·용매 3

HCID 23938Palladium촉매HCID 702Ethanol용매HCID 6344Dichloromethane용매

실험 절차

To a solution of 2-(5-{6-[4-(2-{1-[2-Methoxycarbonylamino-2-(tetrahydro-pyran-4-yl)-acetyl]-pyrrolidin-2-yl}-3H-imidazol-4-yl)-phenyl]-naphthalen-2-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.25 g, 0.36 mmol) in EtOH (3.5 mL) was added Palladium on carbon (10%, 0.42 g, 0.39 mmol) and Potassium Carbonate (0.10 g, 0.70 mmol). The slurry was stirred at room temperature under an atmosphere of H2 for 72 h. The slurry was filtered through celite and washed with EtOH. The filtrate was concentrated to an oil and diluted with CH2Cl2 (3 mL). Methoxycarbonylamino-phenyl-acetic acid (0.11 g, 0.54 mmol) and Potassium Phosphate (0.08 g, 0.35 mmol) were added and the resulting slurry was cooled to 0° C. (external, ice). COMU (0.19 g, 0.44 mmol) was added and the reaction was stirred at 0° C. for 2 h. The slurry was diluted with CH2Cl2 and filtered through celite. The filtrate was concentrated and purified by column chromatography (SiO2, 30→100% EtOAc (10% MeOH) in Hexanes to 60% MeOH in EtOAc) to provide 2-{5-[6-(4-{2-[1-(2-Methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carboxylic acid tert-butyl ester (0.20 g, 74%). LCMS-ESI+: calc'd for C45H47N7O5: 765.36 (M+); Found: 766.64 (M+H+).

후처리

  1. filtrationThe slurry was filtered through celite
  2. washwashed with EtOH
  3. concentrationThe filtrate was concentrated to an oil
  4. additiondiluted with CH2Cl2 (3 mL)
  5. temperaturethe resulting slurry was cooled to 0° C. (external, ice)
  6. stirringthe reaction was stirred at 0° C. for 2 h
  7. filtrationfiltered through celite
  8. concentrationThe filtrate was concentrated
  9. custompurified by column chromatography (SiO2, 30→100% EtOAc (10% MeOH) in Hexanes to 60% MeOH in EtOAc)

출처 및 근거

ORD 기록
ord-d601ccc172614c77bad936c205660329
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09156823B2

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