Imidazole → (2S)-(2R,3S,4R,5R)-2-((((((2R,3S,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-2-((phosphonooxy)methyl)tetrahydrofuran-3-yl)oxy)(hydroxy)phosphoryl)oxy)methyl)-5-(6-amino-9H-purin-9-yl)-4-hydroxytetrahydrofuran-3-yl 2-methoxy-3-phenylpropanoate

HRID 1482191

반응식

HRID 1482191 반응식
[CH2:1]1[C@H:5]([N:6]2[C:11](=[O:12])[N:10]=[C:9]([NH2:13])[CH:8]=[CH:7]2)[O:4][C@H:3]([CH2:14][O:15][P:16]([OH:19])([OH:18])=[O:17])[C@H:2]1[O:20][P:21]([O:24][CH2:25][C@H:26]1[O:30][C@@H:29]([N:31]2[C:35]3[N:36]=[CH:37][N:38]=[C:39]([NH2:40])[C:34]=3[N:33]=[CH:32]2)[C@H:28]([OH:41])[C@@H:27]1[OH:42])([OH:23])=[O:22].[CH3:43][O:44][C@@H:45]([CH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)[C:46](OCC#N)=[O:47].N1C=CN=C1.C(O)(C(F)(F)F)=O>[Cl-].C[N+](C)(C)CCCCCCCCCCCCCCCC.O>[CH3:43][O:44][C@H:45]([CH2:52][C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=1)[C:46]([O:42][C@H:27]1[C@@H:28]([OH:41])[C@H:29]([N:31]2[CH:32]=[N:33][C:34]3[C:35]2=[N:36][CH:37]=[N:38][C:39]=3[NH2:40])[O:30][C@H:26]1[CH2:25][O:24][P:21]([O:20][C@H:2]1[CH2:1][C@H:5]([N:6]2[CH:7]=[CH:8][C:9]([NH2:13])=[N:10][C:11]2=[O:12])[O:4][C@@H:3]1[CH2:14][O:15][P:16]([OH:18])([OH:19])=[O:17])([OH:23])=[O:22])=[O:47]

참가 물질

7

반응물 4

HCID 795ImidazoleHCID 6422Trifluoroacetic acidHCID 1955115'-Phospho-2'-deoxyribocytidylylriboadenosine2회HCID 89668408(S)-cyanomethyl 2-methoxy-3-phenylpropanoate2회

생성물 1

HCID 117741483(2S)-(2R,3S,4R,5R)-2-((((((2R,3S,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-2-((phosphonooxy)methyl)tetrahydrofuran-3-yl)oxy)(hydroxy)phosphoryl)oxy)methyl)-5-(6-amino-9H-purin-9-yl)-4-hydroxytetrahydrofuran-3-yl 2-methoxy-3-phenylpropanoate수율 16.5%

시약·촉매·용매 2

HCID 8154Hexadecyltrimethylammonium chloride촉매HCID 962Water용매

실험 절차

((2R,3S,5R)-5-(4-Amino-2-oxopyrimidin-1(2H)-yl)-3-(((((2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methoxy)(hydroxy)phosphoryl)oxy)tetrahydrofuran-2-yl)methyl dihydrogenphosphate (Compound 1h, 0.32 g, 0.50 mmol) and (S)-cyanomethyl 2-methoxy-3-phenylpropanoate (Compound 7b, 0.44 g, 2.01 mmol) were added to a solution of imidazole (3.40 g, 50.00 mmol) and N,N,N-trimethylhexadecan-1-aminium chloride (3.20 g, 10.00 mmol) dissolved in water (30 ml), and the mixture was stirred at room temperature for 30 minutes. TFA (1.0 ml) was added to the reaction solution, followed by concentration. The resulting residue was purified by preparative HPLC (0.05% aqueous TFA solution:acetonitrile=84:16→60:40) to afford the title compound (66 mg, 16%).

후처리

  1. concentrationfollowed by concentration
  2. customThe resulting residue was purified by preparative HPLC (0.05% aqueous TFA solution:acetonitrile=84:16→60:40)

출처 및 근거

ORD 기록
ord-e06a72f5ee824b188c7d9d3bb4c1a019
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09409952B2

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