Methanesulfonyl chloride → HCID 44397699, compound

HRID 29274Notes

Reaction equation

HRID 29274 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.[CH3:46][S:47](Cl)(=[O:49])=[O:48]>C(Cl)Cl>[CH3:46][S:47]([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:49])=[O:48]

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 44397439HCID 44397439, compound

Product 1

HCID 44397699HCID 44397699, 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 with N,N-diisopropylethylamine (6.0 equiv.) and methanesulfonyl chloride (3.0 equiv.). The reaction was allowed to proceed at room temperature for 1 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-[(methylsulfonyl)amino]-1-benzofuran-2-yl}carbonyl)amino]-1,1′-biphenyl-4-yl}sulfonyl)-L-valine LCMS MH+ (m/z) 586. 1H NMR (300 MHz, DMSO-d6): δ 10.53 ppm (s, 1H), 9.59 ppm (s, 1H), 7.78-7.16 ppm (m, 12H), 3.30 ppm (m, 1H), 1.87 ppm (m, 1H), 0.63 ppm (m, 6H).

Workup

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

Sources & evidence

ORD record
ord-cf0f0e8b6da246968a980ee30e6401d3
Source dataset
uspto-grants-2008_09
Patent number
US07420001B2

Reaction notes

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