(S)-2-((S)-N,2-Dimethylhexanamido)pent-4-enoic acid → (S)-N-((S)-1-((2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-dichloro-phenyl)-3-hydroxybutan-2-ylamino)-1-oxopent-4-en-2-yl)-N,2-dimethylhexan-amide

HRID 501760Notes

Reaction equation

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

Participants

Reactant 2

HCID 59423740(S)-2-((S)-N,2-Dimethylhexanamido)pent-4-enoic acid

HCID 59423767(2R,3S)-1-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-3-amino-4-(3,5-dichloro-phenyl)butan-2-ol

Product 1

HCID 68466886(S)-N-((S)-1-((2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-dichloro-phenyl)-3-hydroxybutan-2-ylamino)-1-oxopent-4-en-2-yl)-N,2-dimethylhexan-amide

Procedure

Step DO (1): (S)-2-((S)-N,2-Dimethylhexanamido)pent-4-enoic acid (26.5 mg, 0.11 mmoles, diastereomer A from Preparation D) and (2R,3S)-1-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-3-amino-4-(3,5-dichloro-phenyl)butan-2-ol (47 mg, from Preparation BG) were coupled by a procedure analogous to Step DL (1) to afford 29.5 mg of (S)-N-((S)-1-((2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-dichloro-phenyl)-3-hydroxybutan-2-ylamino)-1-oxopent-4-en-2-yl)-N,2-dimethylhexan-amide as a clear oil. LC-MS Rt 2.25 min (method A), (M+H)+=674.2, 676; 1H NMR (500 MHz, CDCl3) δ 7.30 (d, J=8.2, 1H) 7.18 (m, 1H) 7.09 (s, 1H) 7.06 (s, 1H) 6.94 (s, 1H) 6.84 (d, J=8.2, 1H) 6.37 (d, J=8.8, 1H) 5.95 (m, 1H) 5.58 (m, 1H) 5.30 (m, 1H) 5.18 (d, J=10.3, 1H) 5.10-4.97 (m, 3H) 4.77 (m, 1H) 4.18-4.05 (m, 3H) 3.81 (s, 1H) 3.80 (s, 3H) 3.46 (m, 1H) 3.13 (d of d, J=15, 2, 3.1, 1H) 3.01 (d of d, J=14.6, 3.6, 1H) 2.87 (s, 1H) 2.86-2.78 (m, 2H) 2.74-2.45 (m, 7H) 2.42-2.32 (m, 1H) 1.93 (m, 1H) 1.65-1.45 (m, 1H) 1.37-1.13 (m, 6H) 1.02 (d, J=7.0, 2H) 0.95 (d, J=7.0, 1H) 0.87 (m, 4H).

Sources & evidence

ORD record: ord-b5e548ebcd8c4427898ff89abd3e0ca6
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07772221B2

Reaction notes

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