Diisopropylethylamine → (2S)-4-Amino-4-oxo-2-[(2-quinolinylcarbonyl)amino]butanamido N-(1S,2R)-1-benzyl-3-[(cyclopentyloxy)(1H-indazol-6-ylsulfonyl)amino]-2-hydroxypropylcarbamate

HRID 29177Notes

Reaction equation

HRID 29177 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.C([N:63]1[C:71]2[C:66](=[CH:67][CH:68]=[C:69]([S:72](Cl)(=[O:74])=[O:73])[CH:70]=2)[CH:65]=[N:64]1)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(N(C(C)C)CC)(C)C>O1CCCC1>[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:72]([C:69]1[CH:70]=[C:71]2[C:66]([CH:65]=[N:64][NH:63]2)=[CH:67][CH:68]=1)(=[O:74])=[O:73])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 22997196HCID 22997196, compoundHCID 86585035(2S)-4-Amino-4-oxo-2-[(2-quinolinylcarbonyl)amino]butanamido N-(1S,2R)-1-benzyl-3-[(cyclopentyloxy)amino]-2-hydroxypropylcarbamate

Product 1

HCID 86585036(2S)-4-Amino-4-oxo-2-[(2-quinolinylcarbonyl)amino]butanamido N-(1S,2R)-1-benzyl-3-[(cyclopentyloxy)(1H-indazol-6-ylsulfonyl)amino]-2-hydroxypropylcarbamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(2S)-4-Amino-4-oxo-2-[(2-quinolinylcarbonyl)-amino]butanamido N-(1S,2R)-1-benzyl-3-[(cyclopentyloxy)-amino]-2-hydroxypropylcarbamate (Step 1, Example 51), (44 mg, 0.0825 mmol), 1-trityl-1H-indazole-6-sulfonyl chloride (38 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 compound was deprotected as described in Example 57 and purified by preparative silica gel TLC using 90:10 chloroform:methanol as an eluent to provide the desired product as a white film (9 mg, 0.013 mmol, 15%). 1HNMR (d6-DMSO) δ: 8.84 (d, J=8.5 Hz, 1H), 8.61 (d, J=8.5 Hz, 1H), 8.31-6.95 (m, 13H), 5.24 (d, J=6.6 Hz, 1H), 4.81-4.72 (m, 2H), 3.97 (bs, 1H), 3.68 (bs, 1H), 3.40-1.20 (m, 15H). MS(ES): 714 (M+1), 712 (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. custompurified by preparative silica gel

Sources & evidence

ORD record
ord-b0871e3406064c05b5c3412d3ab2f3d3
Source dataset
uspto-grants-2008_09
Patent number
US07419967B2

Reaction notes

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