Acetic Acid → (2S,4R)-1-(2-(1H-imidazol-5-yl)acetyl)-4-(benzylamino)-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide

HRID 1630287노트

반응식

HRID 1630287 반응식
[NH:1]1[C:5]([CH2:6][C:7]([N:9]2[CH2:13][C@H:12]([NH2:14])[CH2:11][C@H:10]2[C:15]([NH:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)=[CH:20][CH:19]=2)=[O:16])=[O:8])=[CH:4][N:3]=[CH:2]1.[CH:32](=O)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>[OH-].[Na+].C(Cl)Cl>[NH:1]1[C:5]([CH2:6][C:7]([N:9]2[CH2:13][C@H:12]([NH:14][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH2:11][C@H:10]2[C:15]([NH:17][C:18]2[CH:19]=[CH:20][C:21]([O:24][C:25]3[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=3)=[CH:22][CH:23]=2)=[O:16])=[O:8])=[CH:4][N:3]=[CH:2]1

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 240BenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 67010250(2S,4R)-1-(2-(1H-imidazol-5-yl)acetyl)-4-amino-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide

생성물 1

HCID 67009528(2S,4R)-1-(2-(1H-imidazol-5-yl)acetyl)-4-(benzylamino)-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide수율 30.3%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 14798Sodium Hydroxide용매

실험 절차

A flask was charged with (2S,4R)-1-(2-(1H-imidazol-5-yl)acetyl)-4-amino-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide (150 mg, 0.302 mmol), benzaldehyde (0.031 mL, 0.30 mmol), methylene chloride (5 mL), acetic acid (0.140 mL, 2.45 mmol) and sodium triacetoxyborohydride (22 mg, 0.45 mmol). The reaction mixture was stirred at ambient temperature for 16 hours and then diluted with 2N sodium hydroxide (10 mL). The dilution was extracted with ethyl acetate (20 mL) and the extract was washed with brine (10 mL), dried over anhydrous sodium sulfate, filtered and concentrated. Product was purified from the residue by reverse phase HPLC to give Compound 173, (2S,4R)-1-(2-(1H-imidazol-5-yl)acetyl)-4-(benzylamino)-N-(4-(4-fluorophenoxy)phenyl)pyrrolidine-2-carboxamide (47 mg, 0.091 mmol, 30%), as an off-white solid. 1H-NMR (400 MHz, DMSO-D6): 11.94 (s, 1H), 10.09 (s, 1H), 7.60 (d, 2H), 7.34-7.28 (m, 4H), 7.25-7.17 (m, 3H), 7.03-6.96 (m, 6H), 4.48 (t, 1H), 3.60-3.32 (m, 7H), 2.12-1.99 (m, 2H). MS (EI) for C29H28FN5O3. found 513.9 (MH+).

후처리

  1. extractionThe dilution was extracted with ethyl acetate (20 mL)
  2. washthe extract was washed with brine (10 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customProduct was purified from the residue by reverse phase HPLC

출처 및 근거

ORD 기록
ord-13ee8c8d2607483c8622754e17a270e9
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08791102B2

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