(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 → (S)-N-((2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-dichlorophenyl)-3-hydroxybutan-2-yl)-2-(3,3,3-trifluoro-N-methylpropylsulfonamido)pent-4-enamide

HRID 501759Notes

Reaction equation

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

Participants

Reactant 2

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

HCID 59423777(S)-2-(3,3,3-Trifluoro-N-methyl-propylsulfonamido)pent-4-enoic acid

Product 1

HCID 68465456(S)-N-((2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-dichlorophenyl)-3-hydroxybutan-2-yl)-2-(3,3,3-trifluoro-N-methylpropylsulfonamido)pent-4-enamideYield 24%

Procedure

Step DM (1): (S)-2-(3,3,3-Trifluoro-N-methyl-propylsulfonamido)pent-4-enoic acid (33 mg, 0.11 mmol, from Preparation J) was coupled with (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 (50 mg, from Preparation BG) by a procedure analogous to Step DL (1) to afford 19.1 mg of (S)-N-((2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-dichlorophenyl)-3-hydroxybutan-2-yl)-2-(3,3,3-trifluoro-N-methylpropylsulfonamido)pent-4-enamide as a clear oil. LC-MS Rt 2.10 min (method A), (M+H)+=722.1, 724.0; HRMS (M+H)+=722.2031; 1H NMR (500 MHz, CDCl3) δ 7.35 (d, J=8.2, 1H) 7.18 (s, 1H) 7.08 (s, 2H) 6.95 (d of d, J=8.5, 2.1, 1H) 6.78 (d, J=8.8, 1H) 5.91 (m, 1H) 5.66 (m, 1H) 5.31 (d, J=17.4, 1H) 5.24-5/12 (m, 3H) 4.82 (d, J=4.6, 1H) 4.72 (br d, J=6.7, 1H) 4.21 (d of d, J=5.2, 5.2, 1H) 4.10 (m, 3H) 4.01 (m, 3H) 3.80 (s, 3H) 3.26 (d, J=12.2, 1H) 3.10 (m, 5H) 2.90-2.80 (m, 2H) 2.72-2.50 (m, 5H0, 2.56 (s, 3H) 2.44-2.31 (m, 2H) 1.32 (t, J=7.3, 2H) 1.24 (s, 1H).

Sources & evidence

ORD record: ord-db496179bc8f4265909fab8dcfae2ec0
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07772221B2

Reaction notes

Loading…