(2R,3S)-N-(3-(allyloxy)-6-phenoxy-2,3-dihydro-1H-inden-1-yl)-2-(tert-butyldimethylsilyloxy)-4-phenylbutane-1,3-diamine → (2S)-N-((2S,3R)-4-(3-(allyloxy)-6-phenoxy-2,3-dihydro-1H-inden-1-ylamino)-3-(tert-butyldimethylsilyloxy)-1-phenylbutan-2-yl)-2-(N-methylhexanamido)hex-5-enamide

HRID 501765Notes

Reaction equation

C(O[C@H]1C2C(=CC(Br)=CC=2)[C@@H](NC[C@@H](O)[C@@H](N)CC2C=C(F)C=C(F)C=2)C1)C=C.[CH3:30][N:31]([C@@H:39]([CH2:43][CH2:44][CH:45]=[CH2:46])[C:40]([OH:42])=O)[C:32](=[O:38])[CH2:33][CH2:34][CH2:35][CH2:36][CH3:37].[CH2:47]([O:50][CH:51]1[C:59]2[C:54](=[CH:55][C:56]([O:60][C:61]3[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=3)=[CH:57][CH:58]=2)[CH:53]([NH:67][CH2:68][C@@H:69]([O:79][Si:80]([C:83]([CH3:86])([CH3:85])[CH3:84])([CH3:82])[CH3:81])[C@@H:70]([NH2:78])[CH2:71][C:72]2[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=2)[CH2:52]1)[CH:48]=[CH2:49]>>[CH2:47]([O:50][CH:51]1[C:59]2[C:54](=[CH:55][C:56]([O:60][C:61]3[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=3)=[CH:57][CH:58]=2)[CH:53]([NH:67][CH2:68][C@@H:69]([O:79][Si:80]([C:83]([CH3:86])([CH3:85])[CH3:84])([CH3:81])[CH3:82])[C@@H:70]([NH:78][C:40](=[O:42])[C@@H:39]([N:31]([CH3:30])[C:32](=[O:38])[CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[CH2:43][CH2:44][CH:45]=[CH2:46])[CH2:71][C:72]2[CH:73]=[CH:74][CH:75]=[CH:76][CH:77]=2)[CH2:52]1)[CH:48]=[CH2:49]

Participants

Reactant 3

HCID 59423729(2R,3S)-N-(3-(allyloxy)-6-phenoxy-2,3-dihydro-1H-inden-1-yl)-2-(tert-butyldimethylsilyloxy)-4-phenylbutane-1,3-diamine

HCID 68465135(2R,3S)-1-((1S,3R)-3-(Allyloxy)-6-bromo-2,3-dihydro-1H-inden-1-ylamino)-3-amino-4-(3,5-difluorophenyl)butan-2-ol2×

HCID 86761152(S)-2-(N-methylhexanamido)hex-5-enoic acid

Product 1

HCID 68465134(2S)-N-((2S,3R)-4-(3-(allyloxy)-6-phenoxy-2,3-dihydro-1H-inden-1-ylamino)-3-(tert-butyldimethylsilyloxy)-1-phenylbutan-2-yl)-2-(N-methylhexanamido)hex-5-enamideYield 40%

Procedure

Step EX (1): (S)-2-(N-methylhexanamido)hex-5-enoic acid (500 mg, 2.1 mmol) and (2R,3S)-N1-(3-(allyloxy)-6-phenoxy-2,3-dihydro-1H-inden-1-yl)-2-(tert-butyldimethylsilyloxy)-4-phenylbutane-1,3-diamine (1.2 g, 2.1 mmol, from Preparation BC) were coupled using a procedure analogous to Step CA (1) to afford 650 mg (40% yield) of (2S)-N-((2S,3R)-4-(3-(allyloxy)-6-phenoxy-2,3-dihydro-1H-inden-1-ylamino)-3-(tert-butyldimethylsilyloxy)-1-phenylbutan-2-yl)-2-(N-methylhexanamido)hex-5-enamide. LC-MS (M+H)+=782.65; 1H NMR (300 MHz, CDCl3) δ ppm 0.0 (m, 6H) 0.6-0.9 (m, 12H) 1.1-1.4 (m, 6H) 1.4-1.6 (m, 3H) 1.7-2.3 (m, 6H) 2.3-2.4 (s, 3H) 2.5-2.9 (m, 4H) 3.5-3.8 (m, 1H) 4.0-4.4 (m, 4H) 4.7-4.8 (m, 1H) 4.8-5.4 (m, 4H) 5.6-6.1 (m, 2H) 6.9-7.4 (m, 13H).

Sources & evidence

ORD record: ord-642547c2d21e421bb15b694528222336
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07772221B2

Reaction notes

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