HCID 10131699, compound → (2R,3S)-1-((1R,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-3-amino-4-(3,5-difluorophenyl)butan-2-ol

HRID 501692Notes

Reaction equation

HRID 501692 reaction equation
C(O[C@H]1C2C(=CC(OC)=CC=2)[C@H](N)C1)C=C.FC1C=C(C[C@H](NC(=O)OCC2C=CC=CC=2)[C@H]2CO2)C=C(F)C=1.[CH2:41]([O:44][C@@H:45]1[C:53]2[C:48](=[CH:49][C:50]([O:54][CH3:55])=[CH:51][CH:52]=2)[C@@H:47]([NH:56][CH2:57][C@@H:58]([OH:80])[C@@H:59]([NH:69]C(=O)OCC2C=CC=CC=2)[CH2:60][C:61]2[CH:66]=[C:65]([F:67])[CH:64]=[C:63]([F:68])[CH:62]=2)[CH2:46]1)[CH:42]=[CH2:43].C(O[C@H]1C2C(=CC(OC)=CC=2)[C@H](NC[C@@H](O)[C@@H](NC(=O)OCC2C=CC=CC=2)CC2C=C(F)C=C(F)C=2)C1)C=C>>[CH2:41]([O:44][C@H:45]1[C:53]2[C:48](=[CH:49][C:50]([O:54][CH3:55])=[CH:51][CH:52]=2)[C@H:47]([NH:56][CH2:57][C@@H:58]([OH:80])[C@@H:59]([NH2:69])[CH2:60][C:61]2[CH:62]=[C:63]([F:68])[CH:64]=[C:65]([F:67])[CH:66]=2)[CH2:46]1)[CH:42]=[CH2:43]

Participants

5

Reactant 4

HCID 10131699HCID 10131699, compoundHCID 68466192trans-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-amineHCID 86622323benzyl (2S,3R)-4-((1S,3S)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-ylcarbamateHCID 86622324benzyl (2S,3R)-4-((1R,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-ylcarbamate

Product 1

HCID 59423706(2R,3S)-1-((1R,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-3-amino-4-(3,5-difluorophenyl)butan-2-olYield 69%

Procedure

Step X (3): trans-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-amine from Step X (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 to provide 900 mg (69% yield) of a mixture of benzyl (2S,3R)-4-((1S,3S)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-ylcarbamate and benzyl (2S,3R)-4-((1R,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-ylcarbamate. LRMS (M+H)+=553.3; 1H NMR (500 MHz, CDCl3) δ ppm 1.87-2.05 (m, 1H) 2.38-2.50 (m, 1H) 2.69-2.92 (m, 3H) 2.96-3.12 (m, 1H) 3.41-3.51 (m, 1H) 3.72-3.91 (m, 4H) 4.01 (t, J=5.49 Hz, 2H) 4.37-4.47 (m, 1H) 4.80 (d, J=9.16 Hz, 1H) 4.92 (dd, J=15.26, 4.58 Hz, 1H) 4.97-5.08 (m, 2H) 5.17 (d, J=10.38 Hz, 1H) 5.23-5.33 (m, 1H) 5.84-5.99 (m, 1H) 6.60-6.68 (m, 1H) 6.74 (d, J=6.41 Hz, 2H) 6.82 (dd, J=8.24, 1.83 Hz, 1H) 6.91 (s, 1H) 7.20-7.38 (m, 7H).

Workup

  1. customThe crude product was purified

Sources & evidence

ORD record
ord-41cfc2d6d2324e7b98c3749c9c229dd4
Source dataset
uspto-grants-2010_08
Patent number
US07772221B2

Reaction notes

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