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

HRID 1052539Notes

Reaction equation

[Cl-].[CH3:2][C:3]1[CH:4]=[CH:5][N:6]2[C:11]=1[C:10](=[O:12])[N:9]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:8]([C@@H:19]([NH3+:21])[CH3:20])=[N:7]2.Cl[C:23]1[C:24]2[C:31]([S:32][C:33]3[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=3[O:40][CH3:41])=[CH:30][N:29]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:49])([CH3:48])[CH3:47])[C:25]=2[N:26]=[CH:27][N:28]=1.[F-].[Cs+].C(N(CC)C(C)C)(C)C>C(O)(C)(C)C>[F:39][C:37]1[CH:36]=[CH:35][C:34]([O:40][CH3:41])=[C:33]([S:32][C:31]2[C:24]3[C:23]([NH:21][C@H:19]([C:8]4[N:9]([C:13]5[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=5)[C:10](=[O:12])[C:11]5=[C:3]([CH3:2])[CH:4]=[CH:5][N:6]5[N:7]=4)[CH3:20])=[N:28][CH:27]=[N:26][C:25]=3[N:29]([CH2:42][O:43][CH2:44][CH2:45][Si:46]([CH3:48])([CH3:47])[CH3:49])[CH:30]=2)[CH:38]=1

Participants

Conditions

Temperature: 125 °C

Procedure

(S)-1-(5-Methyl-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethanaminium chloride (39 mg, 0.13 mmol) was treated with 4-chloro-5-((5-fluoro-2-methoxyphenyl)thio)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (56 mg, 0.13 mmol), cesium fluoride (8 mg, 0.05 mmol), N,N-diisopropylethylamine (201 μl, 1.15 mmol) and tert-butanol (0.78 ml) as a solvent according to Preparation 13 but heating the reaction mixture at 125° C. overnight. The residue was purified using SP1® Purification System (0% to 40%, hexane-ethyl acetate) to give 63 mg (73% yield) of the title compound.

Workup

customaccording to Preparation 13
customThe residue was purified
customSP1® Purification System (0% to 40%, hexane-ethyl acetate)

Sources & evidence

ORD record: ord-1191c2b1b4f846a09456e25ece816b61
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09388189B2

Reaction notes

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