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

HRID 1062901ノート

反応式

HRID 1062901 の反応式
[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]

参加物

7

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 887Methanol溶媒2 回HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

(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.

後処理

  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

出典と根拠

ORDレコード
ord-eb5ded51a5344b0e88d0fef660bc384b
出典データセット
uspto-grants-2005_11
特許番号
US06962934B2

反応ノート

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