Methanol → isoxazol-5-ylmethyl N-[(1S,2S,4S)-1-benzyl-2-hydroxy-4-[[(2S)-2-[[(2-isopropyloxazol-4-yl)methyl-methyl-carbamoyl]amino]-3-methyl-butanoyl]amino]-5-phenyl-pentyl]carbamate

HRID 1861189Notes

Reaction equation

HRID 1861189 reaction equation
[NH2:1][C@@H:2]([CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)[CH2:3][C@H:4]([OH:23])[C@@H:5]([NH:13][C:14]([O:16][CH2:17][C:18]1[O:22][N:21]=[CH:20][CH:19]=1)=[O:15])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH3:31][N:32]([C:42]([NH:44][C@H:45]([C:49](O)=[O:50])[CH:46]([CH3:48])[CH3:47])=[O:43])[CH2:33][C:34]1[N:35]=[C:36]([CH:39]([CH3:41])[CH3:40])[O:37][CH:38]=1.CO>ClCCl>[CH3:31][N:32]([C:42]([NH:44][C@H:45]([C:49]([NH:1][C@@H:2]([CH2:24][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)[CH2:3][C@H:4]([OH:23])[C@@H:5]([NH:13][C:14]([O:16][CH2:17][C:18]1[O:22][N:21]=[CH:20][CH:19]=1)=[O:15])[CH2:6][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1)=[O:50])[CH:46]([CH3:48])[CH3:47])=[O:43])[CH2:33][C:34]1[N:35]=[C:36]([CH:39]([CH3:41])[CH3:40])[O:37][CH:38]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 10851544N-((N-methyl-N-((2-isopropyl-4-oxazolyl)methyl)amino)carbonyl)-L-valineHCID 57164722(2S,3S,5S)-5-amino-2-(N-((5-isoxazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane

Product 1

HCID 482942isoxazol-5-ylmethyl N-[(1S,2S,4S)-1-benzyl-2-hydroxy-4-[[(2S)-2-[[(2-isopropyloxazol-4-yl)methyl-methyl-carbamoyl]amino]-3-methyl-butanoyl]amino]-5-phenyl-pentyl]carbamateYield 80%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Using the procedure of Example 1U but replacing (2S,3S,5S)-5-amino-2-(N-((5-thiazolyl)-methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane with (2S,3S,5S)-5-amino-2-(N-((5-isoxazolyl)methoxycarbonyl)amino)-1,6-diphenyl-3-hydroxyhexane and replacing N-((N-methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carbonyl)-L-valine with N-((N-methyl-N-((2-isopropyl-4-oxazolyl)methyl)amino)carbonyl)-L-valine provided, after silica gel chromatography using a gradient of 1-4% methanol in dichloromethane, 225 mg (80%) of the desired compound. 1H NMR (DMSO-d6) δ 0.74 (d, J=6.9 Hz, 6H), 1.23 (d, J=6.9 Hz, 6H), 1.35-1.54 (m, 2H), 1.80-1.95 (m, 1 H), 2.55-2.73 (m, 4H), 2.83 (s, 3H), 2.94-3.09 (m, 1H), 3.53-3.63 (m, 1H), 3.73-3.86 (m, 1H), 3.92 (t, J=8.4 Hz, 1H), 4.08-4.34 (m, 3H), 4.65 (d, J=6 Hz, 1H), 5.04 (s, 2H), 5.91 (d, J=9 Hz, 1H), 6.29 (d, J=2.4 Hz, 1H), 7.01 (d, J=9 Hz, 1H), 7.06-7.27 (m, 10H), 7.69 (d, J=9 Hz, 1H), 7.77 (s, 1H), 8.52 (d, J=2.4 Hz, 1H). Mass spectrum: (M+H)+=689; (M+NH4)+=706. Anal. Calcd for C37H48N6O7: C, 64.52; H, 7.02; N, 12.20. Found: C, 64.52; H, 7.14; N, 12.06.

Workup

  1. customprovided

Sources & evidence

ORD record
ord-2d5ab6babdf5420da3c6a84f4f2a394e
Source dataset
uspto-grants-2003_03
Patent number
US06531610B1

Reaction notes

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