Acetyl chloride → HCID 44397568, compound

HRID 29275Notes

Reaction equation

HRID 29275 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([C:10]([NH:12][C:13]3[CH:18]=[CH:17][C:16]([C:19]4[CH:24]=[CH:23][C:22]([S:25]([NH:28][C@H:29]([C:33]([OH:35])=[O:34])[CH:30]([CH3:32])[CH3:31])(=[O:27])=[O:26])=[CH:21][CH:20]=4)=[CH:15][CH:14]=3)=[O:11])=[CH:7][C:6]=2[CH:36]=1.C(N(CC)C(C)C)(C)C.[C:46](Cl)(=[O:48])[CH3:47]>C(Cl)Cl>[C:46]([NH:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([C:10]([NH:12][C:13]3[CH:18]=[CH:17][C:16]([C:19]4[CH:20]=[CH:21][C:22]([S:25]([NH:28][C@H:29]([C:33]([OH:35])=[O:34])[CH:30]([CH3:32])[CH3:31])(=[O:26])=[O:27])=[CH:23][CH:24]=4)=[CH:15][CH:14]=3)=[O:11])=[CH:7][C:6]=2[CH:36]=1)(=[O:48])[CH3:47]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 44397439HCID 44397439, compound

Product 1

HCID 44397568HCID 44397568, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N-[(4′-{[(5-amino-1-benzofuran-2-yl)carbonyl]amino}-1,1′-biphenyl-4-yl)sulfonyl]-L-valine-Wang resin (0.3 g), from Example 7, was suspended in methylene chloride (6 mL). To the suspension was added N,N-diisopropylethylamine (6.0 equiv.) and acetyl chloride (3.0 equiv.). The reaction was allowed to proceed at room temperature for 0. h and the reagent was removed by filtration. The resin was washed with methylene chloride (2×), methanol and methylene chloride (2×) before being treated with a 95% solution of TFA in methylene chloride (5 mL) and agitated at room temperature for 2 h. The solution was collected by filtration and the solvent was removed via vacuum. The crude product was then purified by flash chromatography to give N-{[4′-({[5-(acetylamino)-1-benzofuran-2-yl]carbonyl}amino)-1,1′-biphenyl-4-yl]sulfonyl}-L-valine. LCMS MH+ (m/z) 550. 1H NMR (300 MHz, DMSO-d6): δ 10.50 ppm (s, 1H), 9.92 ppm (s, 1H), 8.00-7.34 ppm (m, 12H), 3.33 ppm (m, 1H), 1.89 ppm (s, 3 H), 1.76 ppm (m, 1H), 0.63 ppm (m, 6H).

Workup

  1. customto proceed at room temperature for 0
  2. customh and the reagent was removed by filtration
  3. washThe resin was washed with methylene chloride (2×), methanol and methylene chloride (2×)
  4. additionbefore being treated with a 95% solution of TFA in methylene chloride (5 mL)
  5. filtrationThe solution was collected by filtration
  6. customthe solvent was removed via vacuum
  7. customThe crude product was then purified by flash chromatography

Sources & evidence

ORD record
ord-ef30051831be4e569dec2f007275f65c
Source dataset
uspto-grants-2008_09
Patent number
US07420001B2

Reaction notes

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