Acetic Acid → N-[(2S)-2-({3-[(dipropylamino)carbonyl]benzoyl}amino)-4-methylpentyl]-L-alanyl-N1-isobutyl-L-valinamide

HRID 1062901노트

반응식

HRID 1062901 반응식
[CH2:1]([N:4]([CH2:42][CH2:43][CH3:44])[C:5]([C:7]1[CH:8]=[C:9]([CH:39]=[CH:40][CH:41]=1)[C:10]([NH:12][C@@H:13]([CH2:32][C:33]1[CH:38]=CC=C[CH:34]=1)[CH2:14][NH:15][C@H:16]([C:18]([NH:20][C@H:21]([C:25]([NH:27][CH2:28][CH:29]([CH3:31])[CH3:30])=[O:26])[CH:22]([CH3:24])[CH3:23])=[O:19])[CH3:17])=[O:11])=[O:6])[CH2:2][CH3:3].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1.C(OCC)(=O)C.CO>[CH2:42]([N:4]([CH2:1][CH2:2][CH3:3])[C:5]([C:7]1[CH:8]=[C:9]([CH:39]=[CH:40][CH:41]=1)[C:10]([NH:12][C@@H:13]([CH2:32][CH:33]([CH3:38])[CH3:34])[CH2:14][NH:15][C@H:16]([C:18]([NH:20][C@H:21]([C:25]([NH:27][CH2:28][CH:29]([CH3:30])[CH3:31])=[O:26])[CH:22]([CH3:24])[CH3:23])=[O:19])[CH3:17])=[O:11])=[O:6])[CH2:43][CH3:44]

참가 물질

7

반응물 3

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 9938756N-[(2S)-2-({3-[(dipropylamino)carbonyl]-benzoyl}amino)-3-phenylpropyl]-L-alanyl-N1-isobutyl-L-valinamide

생성물 1

HCID 10175173N-[(2S)-2-({3-[(dipropylamino)carbonyl]benzoyl}amino)-4-methylpentyl]-L-alanyl-N1-isobutyl-L-valinamide수율 32.1%

시약·촉매·용매 3

HCID 887Methanol용매2회HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

(290 mg, 0.84 mmol) in 6 mL of dry THF is added to L-alanyl-N1-isobutyl-L-valinamide (EXAMPLE 1, 205 mg, 0.84 mmol) under nitrogen. To this is added 0.12 mL of acetic acid and sodium triacetoxyborohydride (300 mg, 1.41 mmol), and the mixture is stirred for 3 days. Methanol (1 mL) is added. And the mixture is stirred for 3 more hours. It is diluted with 150 mL of ethyl acetate and 5 mL of methanol, and the organic phase is washed successively with 15 mL of 1 N NaHCO3, water, and brine. The solution is dried with Na2SO4, concentrated, and chromatographed over silica gel. Elution with 4% methanol in dichloromethane, followed by 8% methanol in dichloromethane, afforded the title compound as a white solid (154 mg, 0.27 mmol, 32%). 1H NMR (CDCl3) δ 7.88 (m, 1H), 7.78 (m, 2H), 7.44 (m, 2H), 7.00 (d, J=8 Hz, 1H), 6.69 (br t, J=6 Hz, 1H), 4.14 (dd, J=7, 9 Hz, 1H), 4.04 (m, 1H), 3.46 (m, 2H), 3.16-3.04 (m, 5H), 2.87 (m, 1H), 2.64 (dd, J=4, 13 Hz, 1H), 2.03 (m, 1H), 1.75-1.63 (m, 5H), 1.53 (m, 2H), 1.39 (m, 1H), 1.30 (d, J=7 Hz, 3H), 1.0-0.83 (m, 21H), 0.74 (br t, J=7 Hz, 3H). HRMS (ESI) calcd for C32H55N5O4+H1 574.4332, found 574.4332.

후처리

  1. stirringAnd the mixture is stirred for 3 more hours
  2. washthe organic phase is washed successively with 15 mL of 1 N NaHCO3, water, and brine
  3. dry with materialThe solution is dried with Na2SO4
  4. concentrationconcentrated
  5. customchromatographed over silica gel
  6. washElution with 4% methanol in dichloromethane

출처 및 근거

ORD 기록
ord-eb5ded51a5344b0e88d0fef660bc384b
출처 데이터셋
uspto-grants-2005_11
특허 번호
US06962934B2

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