反応式
[P:1]([O:35]C(C)(C)C)([O:30]C(C)(C)C)([O:3][CH2:4][CH2:5][C:6]#[C:7][C:8]1[C:16]2[C:15]([Cl:17])=[N:14][C:13]([NH2:18])=[N:12][C:11]=2[N:10]([CH2:19][C:20]2[C:25]([CH3:26])=[C:24]([O:27][CH3:28])[C:23]([CH3:29])=[CH:22][N:21]=2)[CH:9]=1)=[O:2].[C:40]([OH:46])([C:42]([F:45])([F:44])[F:43])=[O:41]>C(Cl)Cl>[P:1]([OH:30])([OH:35])([O:3][CH2:4][CH2:5][C:6]#[C:7][C:8]1[C:16]2[C:15]([Cl:17])=[N:14][C:13]([NH2:18])=[N:12][C:11]=2[N:10]([CH2:19][C:20]2[C:25]([CH3:26])=[C:24]([O:27][CH3:28])[C:23]([CH3:29])=[CH:22][N:21]=2)[CH:9]=1)=[O:2].[C:40]([OH:46])([C:42]([F:45])([F:44])[F:43])=[O:41]参加物
実験手順
A solution of 4-(2-amino-4-chloro-7-((4-methoxy-3 5-dimethylpyridin-2-yl)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)but-3-ynyl di-tert-butyl phosphate (see example 43) in DCM ( ) was treated with TFA ( ) at rt for x h. Evaporation gave the title compound as a TFA salt (5 g). The crude was dissolved in a mixture of Et3N (0.7 mL and MeOH (60 mL), loaded on Dowex 50Wx2-400 (20 g, pre-washed with MeOH), and the resin was washed with MeOH (200 mL) to remove the excess TFA. The desired phosphate was released from the resin with Et3N:MeOH 1:10 (200 mL) The solution was concentrated to give the phosphate as an oily triethylamine salt (2.75 g). Crystallization was induced with EtOH (60 mL). The mixture was left at rt for 1.5 h and at −20° C. overnight to give a first crop of crystals (0.64 g). The mixture was concentrated and the crystallization procedure was repeated to give a second crop (0.74 g). The combined triethylamine salts (1274 mg) were dissolved in MeOH (50 mL) with the help of Et3N (326 μL) and treated with a 1.0 M solution of NaGH in MeOH (4.68 mL). Evaporation and drying on high vacuum overnight gave the title compound as a solid sodium salt. HPLC Rt=4.21 mm.
後処理
- customEvaporation
出典と根拠
- ORDレコード
- ord-8982de31c125445c8ac2eaf6a3cd2c13
- 出典データセット
- uspto-grants-2009_06
- 特許番号
- US07544672B2
関連ノート
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