(S)-2-(N-methylhexanamido)pent-4-enoic acid → N-((2S)-1-((2S,3R)-4-(3-(allyloxy)-6-phenoxy-2,3-dihydro-1H-inden-1-ylamino)-3-(tert-butyldimethylsilyloxy)-1-phenylbutan-2-ylamino)-1-oxopent-4-en-2-yl)-N-methylhexanamide

反応式

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

参加物

反応物 3

HCID 59423702(S)-2-(N-methylhexanamido)pent-4-enoic acid

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 回

生成物 1

HCID 68464877N-((2S)-1-((2S,3R)-4-(3-(allyloxy)-6-phenoxy-2,3-dihydro-1H-inden-1-ylamino)-3-(tert-butyldimethylsilyloxy)-1-phenylbutan-2-ylamino)-1-oxopent-4-en-2-yl)-N-methylhexanamide収率 65.1%

実験手順

Step EW (1): (S)-2-(N-Methylhexanamido)pent-4-enoic acid (420 mg, 1.8 mmol) and (2R,3S)-N1-(3-(allyloxy)-6-phenoxy-2,3-dihydro-1H-inden-1-yl)-2-(tert-butyldimethylsilyloxy)-4-phenylbutane-1,3-diamine (1.0 g, 1.8 mmol, from Preparation BC) were coupled using a procedure analogous to Step CA (1) to afford 900 mg (65% yield) of N-((2S)-1-((2S,3R)-4-(3-(allyloxy)-6-phenoxy-2,3-dihydro-1H-inden-1-ylamino)-3-(tert-butyldimethylsilyloxy)-1-phenylbutan-2-ylamino)-1-oxopent-4-en-2-yl)-N-methylhexanamide. LC-MS (M+H)+=768.65; 1H NMR (300 MHz, CDCl3) δ ppm 0.0 (m, 6H) 0.7-0.9 (m, 12H) 1.0-1.4 (m, 6H) 1.4-1.7 (m, 3H) 1.7-2.3 (m, 4H) 2.4 (s, 3H) 2.5-3.0 (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) 5.5-6.1 (m, 2H) 6.8-7.4 (m, 13H).

出典と根拠

ORDレコード: ord-450924aecc3f435fb5bb59fcef5741e6
出典データセット: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
特許番号: US07772221B2

反応ノート

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