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

HRID 1062901Notes

Reaction equation

HRID 1062901 reaction equation
[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]

Participants

7

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

(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.

Workup

  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

Sources & evidence

ORD record
ord-eb5ded51a5344b0e88d0fef660bc384b
Source dataset
uspto-grants-2005_11
Patent number
US06962934B2

Reaction notes

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