2-Methyloctahydropyrrolo(3,4-c)pyrrole → (1S,4R,5S,15R)-5-(3,5-difluoro-benzyl)-4-hydroxy-19-(5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-14-oxa-2,6-diaza-tricyclo[13.6.1.016,21]docosa-11,16(21),17,19-tetraen-7-one

HRID 501767노트

반응식

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.Br[C:31]1[CH:32]=[CH:33][C:34]2[C@H:35]3[CH2:52][C@@H:49]([C:50]=2[CH:51]=1)[NH:48][CH2:47][C@@H:46]([OH:53])[C@H:45]([CH2:54][C:55]1[CH:60]=[C:59]([F:61])[CH:58]=[C:57]([F:62])[CH:56]=1)[NH:44][C:43](=[O:63])[CH2:42][CH2:41][CH2:40][CH:39]=[CH:38][CH2:37][O:36]3.[CH3:64][N:65]1[CH2:72][CH:71]2[CH:67]([CH2:68][NH:69][CH2:70]2)[CH2:66]1>>[F:62][C:57]1[CH:56]=[C:55]([CH:60]=[C:59]([F:61])[CH:58]=1)[CH2:54][C@@H:45]1[NH:44][C:43](=[O:63])[CH2:42][CH2:41][CH2:40][CH:39]=[CH:38][CH2:37][O:36][C@@H:35]2[CH2:52][C@@H:49]([C:50]3[CH:51]=[C:31]([N:69]4[CH2:70][CH:71]5[CH:67]([CH2:66][N:65]([CH3:64])[CH2:72]5)[CH2:68]4)[CH:32]=[CH:33][C:34]=32)[NH:48][CH2:47][C@H:46]1[OH:53]

참가 물질

반응물 3

HCID 129585332-Methyloctahydropyrrolo(3,4-c)pyrrole

HCID 68464298(1S,4R,5S,15R)-19-bromo-5-(3,5-difluoro-benzyl)-4-hydroxy-14-oxa-2,6-diaza-tricyclo[13.6.1.016,21]docosa-11,16(21),17,19-tetraen-7-one

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-ol2회

생성물 1

HCID 67573781(1S,4R,5S,15R)-5-(3,5-difluoro-benzyl)-4-hydroxy-19-(5-methyl-hexahydro-pyrrolo[3,4-c]pyrrol-2-yl)-14-oxa-2,6-diaza-tricyclo[13.6.1.016,21]docosa-11,16(21),17,19-tetraen-7-one수율 46%

실험 절차

Step FG (1): The title compound (80 mg) was prepared in 46% yield via Ullman type coupling of (1S,4R,5S,15R)-19-bromo-5-(3,5-difluoro-benzyl)-4-hydroxy-14-oxa-2,6-diaza-tricyclo[13.6.1.016,21]docosa-11,16(21),17,19-tetraen-7-one (TFA salt of Example 68) and 2-methyloctahydropyrrolo[3,4-c]pyrrole by following a procedure analogous to Step FF (1). LC/MS (M+H)+ 581.43. 1H NMR (400 MHz, CD3OD) δ ppm 1.27 (s, 2H) 1.49 (s, 1H) 1.98-2.06 (m, 2H) 2.23-2.35 (m, 5H) 2.38 (s, 2H) 2.54 (s, 1H) 2.58-2.69 (m, 2H) 2.75 (s, 1H) 2.92 (d, J=12.09 Hz, 4H) 2.99-3.11 (m, 2H) 3.18 (s, 1H) 3.55 (d, J=10.83 Hz, 1H) 3.83 (m, 2H) 3.88-3.98 (m, 2H) 4.05 (d, J=14.10 Hz, 1H) 4.30 (m, 1H) 4.65 (m, 1H) 5.42-5.54 (m, 2H) 6.70-6.77 (m, 5H) 7.19 (t, J=7.43 Hz, 2H). CD3OD

출처 및 근거

ORD 기록: ord-4d669894934f4f1896a1ab00c9b10670
출처 데이터셋: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
특허 번호: US07772221B2

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