HCID 10131699, compound → benzyl (2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-ylcarbamate

HRID 501691Notes

Reaction equation

HRID 501691 reaction equation
[CH2:1]([O:4][C@H:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH3:15])=[CH:11][CH:12]=2)[C@@H:7]([NH2:16])[CH2:6]1)[CH:2]=[CH2:3].[F:17][C:18]1[CH:19]=[C:20]([CH2:25][C@H:26]([NH:30][C:31](=[O:40])[O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C@H:27]2[CH2:29][O:28]2)[CH:21]=[C:22]([F:24])[CH:23]=1>>[CH2:1]([O:4][C@H:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH3:15])=[CH:11][CH:12]=2)[C@@H:7]([NH:16][CH2:29][C@@H:27]([OH:28])[C@@H:26]([NH:30][C:31](=[O:40])[O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[CH2:25][C:20]2[CH:19]=[C:18]([F:17])[CH:23]=[C:22]([F:24])[CH:21]=2)[CH2:6]1)[CH:2]=[CH2:3]

Participants

3

Reactant 2

HCID 10131699HCID 10131699, compoundHCID 59676150(1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-amine

Product 1

HCID 59676145benzyl (2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-ylcarbamateYield 34%

Procedure

Step W (1): (1S,3R)-3-(Allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-amine from Step U(2) was reacted with benzyl (S)-2-(3,5-difluorophenyl)-1-((S)-oxiran-2-yl)ethylcarbamate according to the conditions described in Step V (1). The crude product was purified using silica gel column chromatography (1-10% MeOH (with 0.1% triethylamine)/chloroform, linear gradient) to provide 1.72 g mg (34% yield) of benzyl (2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-ylcarbamate. HRMS (M+H)+=553.2534; 1H NMR (500 MHz, DMSO-d6) δ 7.21-7.35 (m, 4H) 7.14-7.21 (m, 2H) 7.03 (t, J=9.46 Hz, 1H) 6.87-6.99 (m, 3H) 6.83 (dd, J=8.24, 2.14 Hz, 1H) 5.88-6.00 (m, 1H) 5.30 (dd, J=17.09, 1.83 Hz, 1H) 5.14 (dd, J=10.53, 1.98 Hz, 1H) 4.96-5.02 (m, 1H) 4.83-4.95 (m, 2H) 4.75 (t, J=6.41 Hz, 1H) 4.01-4.13 (m, 2H) 3.91-4.00 (m, 1H) 3.72-3.76 (m, 3H) 3.64-3.72 (m, 1H) 3.44-3.53 (m, 1H) 3.06 (dd, J=13.73, 3.05 Hz, 1H) 2.65-2.75 (m, 1H) 2.54-2.65 (m, 2H) 1.92-2.02 (m, 1H) 1.57-1.67 (m, 1H).

Workup

  1. customThe crude product was purified

Sources & evidence

ORD record
ord-c364947cae0649afba8191fe6e367803
Source dataset
uspto-grants-2010_08
Patent number
US07772221B2

Reaction notes

Loading…