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ノート

反応式

HRID 1482191 の反応式
[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]

参加物

7

反応物 4

HCID 795ImidazoleHCID 6422Trifluoroacetic acidHCID 1955115'-Phospho-2'-deoxyribocytidylylriboadenosine2 回HCID 89668408(S)-cyanomethyl 2-methoxy-3-phenylpropanoate2 回

生成物 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-phenylpropanoate収率 16.5%

試薬・触媒・溶媒 2

HCID 8154Hexadecyltrimethylammonium chloride触媒HCID 962Water溶媒

実験手順

((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%).

後処理

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

出典と根拠

ORDレコード
ord-e06a72f5ee824b188c7d9d3bb4c1a019
出典データセット
uspto-grants-2016_08
特許番号
US09409952B2

反応ノート

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