Acetyl chloride → N-acetyl-N-[(2R)-2-(thiazol-5-ylmethoxycarbonylamino)-3-phenylpropyl]-N-[(2S)-2-(thiazol-5-ylmethoxycarbonylamino)-3-phenylpropyl]amine

HRID 1094694Notes

Reaction equation

HRID 1094694 reaction equation
[S:1]1[C:5]([CH2:6][O:7][C:8]([NH:10][C@H:11]([CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH2:12][NH:13][CH2:14][C@@H:15]([NH:23][C:24]([O:26][CH2:27][C:28]2[S:32][CH:31]=[N:30][CH:29]=2)=[O:25])[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:9])=[CH:4][N:3]=[CH:2]1.C(N(CC)CC)C.[C:47](Cl)(=[O:49])[CH3:48].C(OCC)(=O)C>ClCCCl>[C:47]([N:13]([CH2:14][C@H:15]([NH:23][C:24]([O:26][CH2:27][C:28]1[S:32][CH:31]=[N:30][CH:29]=1)=[O:25])[CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[CH2:12][C@@H:11]([NH:10][C:8]([O:7][CH2:6][C:5]1[S:1][CH:2]=[N:3][CH:4]=1)=[O:9])[CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)(=[O:49])[CH3:48]

Participants

6

Reactant 4

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 60204702N-[(2R)-2-(thiazol-5-ylmethoxycarbonylamino)-3-phenylpropyl]-N-[(2S)-2-(thiazol-5-ylmethoxycarbonylamino)-3-phenylpropyl]amine

Product 1

HCID 60204718N-acetyl-N-[(2R)-2-(thiazol-5-ylmethoxycarbonylamino)-3-phenylpropyl]-N-[(2S)-2-(thiazol-5-ylmethoxycarbonylamino)-3-phenylpropyl]amineYield 60%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

The product from Example 26D (50 mg, 0.088 mmol) in 1,2-dichloroethane (2 mL) was treated with triethylamine (14 μl, 0.097 mmol) and acetyl chloride (6.3 μl, 0.088 mmol) at ambient temperature. After stirring for two hours, the mixture was treated with ethyl acetate (8 mL), wash with aqueous 10% NaHCO3 (2×10 mL), brine (10 mL), dried over sodium sulfate, filtered, and the filtrate was concentrated. The residue was purified on a silica gel cartridge eluting with (chloroform:methanol, 99:1) to provide the title compound (32.1 mg, 60%). 1H NMR (CDCl3) δ 8.78 (d, 2H), 7.83 (d, 2H), 7.32-7.01 (m, 10H), 5.42 (d, 1H), 5.21 (d, 4H), 4.71 (br s, 1H), 4.01 (br s, 1H), 3.85 (m, 2H), 3.35 (m, 1H), 3.22 (dd, 1H), 3.00-2.55 (m, 5H), 1.57 (s, 3H); MS (ESI+) m/z 608 (M+H)+.

Workup

  1. washwash with aqueous 10% NaHCO3 (2×10 mL), brine (10 mL)
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. concentrationthe filtrate was concentrated
  5. customThe residue was purified on a silica gel cartridge
  6. washeluting with (chloroform:methanol, 99:1)

Sources & evidence

ORD record
ord-07922cc67c1348ccbe1a2850c79d3a39
Source dataset
uspto-grants-2012_03
Patent number
US08133892B2

Reaction notes

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