Trifluoroacetic acid → Trifluoroacetic acid

HRID 1984108

Reaktionsgleichung

Reaktionsgleichung von HRID 1984108
[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]

Komponenten

5

Edukt 2

HCID 6422Trifluoroacetic acidHCID 577138544-(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

Produkt 2

HCID 6422Trifluoroacetic acidHCID 57713852Biib-028

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  1. customEvaporation

Quellen und Nachweise

ORD-Eintrag
ord-8982de31c125445c8ac2eaf6a3cd2c13
Quelldatensatz
uspto-grants-2009_06
Patentnummer
US07544672B2

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