Cesium fluoride → (S)-2-(1-((5-Bromo-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)-3-hydroxypropyl)-5-methyl-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one

HRID 1052621Notes

Reaction equation

[Cl-].[OH:2][CH2:3][CH2:4][C@@H:5]([C:7]1[N:12]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:11](=[O:19])[C:10]2=[C:20]([CH3:23])[CH:21]=[CH:22][N:9]2[N:8]=1)[NH3+:6].[Br:24][C:25]1[C:33]2[C:32](Cl)=[N:31][CH:30]=[N:29][C:28]=2[N:27]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[CH:26]=1.[F-].[Cs+].C(N(CC)C(C)C)(C)C>C(O)(C)(C)C>[Br:24][C:25]1[C:33]2[C:32]([NH:6][C@H:5]([C:7]3[N:12]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)[C:11](=[O:19])[C:10]4=[C:20]([CH3:23])[CH:21]=[CH:22][N:9]4[N:8]=3)[CH2:4][CH2:3][OH:2])=[N:31][CH:30]=[N:29][C:28]=2[N:27]([CH2:35][O:36][CH2:37][CH2:38][Si:39]([CH3:42])([CH3:41])[CH3:40])[CH:26]=1

Participants

Conditions

Temperature: 100 °C

Procedure

(S)-3-Hydroxy-1-(5-methyl-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)propan-1-aminium chloride (228 mg, 0.68 mmol) was treated with 5-bromo-4-chloro-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (495 mg, 1.36 mmol), cesium fluoride (41 mg, 0.27 mmol) and N,N-diisopropylethylamine (1.60 ml, 9.19 mmol) in tert-butanol (5.0 ml) according to Preparation 13 but stirring the reaction mixture at 100° C. during 96 h. The residue was purified using SP1® Purification System (0% to 100%, hexane-ethyl acetate) to give 249 mg (57% yield) of the title compound.

Workup

customaccording to Preparation 13
customThe residue was purified
customSP1® Purification System (0% to 100%, hexane-ethyl acetate)

Sources & evidence

ORD record: ord-e2efafe3314d441ab81208160bb842ea
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09388189B2

Reaction notes

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