Diisopropylethylamine → (2S)-4-Amino-4-oxo-2-[(2-quinolinylcarbonyl)amino]butanamido N-(1S,2R)-1-benzyl-3-[(cyclopentyloxy)(2-{(methoxycarbonyl)amino]-1H-benzimidazol-5-ylsulfonyl)amino]-2-hydroxypropylcarbamate

HRID 29176Notes

Reaction equation

HRID 29176 reaction equation
[CH2:1]([C@H:8]([NH:19][C:20](=[O:43])[O:21][NH:22][C:23](=[O:42])[C@@H:24]([NH:29][C:30]([C:32]1[CH:41]=[CH:40][C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[N:33]=1)=[O:31])[CH2:25][C:26]([NH2:28])=[O:27])[C@H:9]([OH:18])[CH2:10][NH:11][O:12][CH:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[S:45]([C:48]1[CH:61]=[CH:60][C:51]2[NH:52][C:53]([NH:55][C:56](=[O:59])[O:57][CH3:58])=[N:54][C:50]=2[CH:49]=1)(=[O:47])=[O:46].C(N(C(C)C)CC)(C)C>O1CCCC1.CO>[CH2:1]([C@H:8]([NH:19][C:20](=[O:43])[O:21][NH:22][C:23](=[O:42])[C@@H:24]([NH:29][C:30]([C:32]1[CH:41]=[CH:40][C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[N:33]=1)=[O:31])[CH2:25][C:26]([NH2:28])=[O:27])[C@H:9]([OH:18])[CH2:10][N:11]([O:12][CH:13]1[CH2:14][CH2:15][CH2:16][CH2:17]1)[S:45]([C:48]1[CH:61]=[CH:60][C:51]2[NH:52][C:53]([NH:55][C:56]([O:57][CH3:58])=[O:59])=[N:54][C:50]=2[CH:49]=1)(=[O:47])=[O:46])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 86585035(2S)-4-Amino-4-oxo-2-[(2-quinolinylcarbonyl)amino]butanamido N-(1S,2R)-1-benzyl-3-[(cyclopentyloxy)amino]-2-hydroxypropylcarbamateHCID 178502049HCID 178502049, compound

Product 1

HCID 178502051(2S)-4-Amino-4-oxo-2-[(2-quinolinylcarbonyl)amino]butanamido N-(1S,2R)-1-benzyl-3-[(cyclopentyloxy)(2-{(methoxycarbonyl)amino]-1H-benzimidazol-5-ylsulfonyl)amino]-2-hydroxypropylcarbamateYield 17%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

(2S)-4-Amino-4-oxo-2-[(2-quinolinylcarbonyl)amino]butanamido N-(1S,2R)-1-benzyl-3-[(cyclopentyloxy)-amino]-2-hydroxypropylcarbamate (Step 1, above), (44 mg, 0.0825 mmol), methyl N-[5-(chlorosulfonyl)-1H-benzimidazol-2-yl]carbamate (24 mg, 0.0825 mmol), and anhydrous diisopropylethylamine (0.05 mL, 0.280 mmol) were combined in anhydrous tetrahydrofuran (3 mL) in a 25 mL round bottomed flask under nitrogen. The reaction was stirred for 24 hours and concentrated in vacuo. Ethyl acetate (30 mL) and water (10 mL) were added and the layers were separated. The organic layer was washed with brine (10 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by preparative silica gel TLC using 90:10 chloroform:methanol as an eluent to provide the desired product as a white solid (11 mg, 0.014 mmol, 17%). 1HNMR (d6-DMSO) δ: 8.86 (d, J=8.4 Hz, 1H), 8.62 (d, J=8.4 Hz, 1H), 8.22-6.94 (m, 12H), 5.19 (d, J=6.2 Hz, 1H), 4.77-4.72 (m, 2H), 4.02-1.35 (m, 17H), 3.80 (s, 3H). MS(ES): 787 (M+1), 785 (M−1).

Workup

  1. concentrationconcentrated in vacuo
  2. additionEthyl acetate (30 mL) and water (10 mL) were added
  3. customthe layers were separated
  4. washThe organic layer was washed with brine (10 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by preparative silica gel

Sources & evidence

ORD record
ord-849e412caab54c81b52ac85994235def
Source dataset
uspto-grants-2008_09
Patent number
US07419967B2

Reaction notes

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