Cesium fluoride → (R)-3-methyl-2-(5-(5-((2-(pyrrolidin-1-yl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-ylamino)-N-(2,2,2-trifluoroethyl)butanamide

HRID 510215Notes

Reaction equation

[CH3:1][CH:2]([CH3:45])[C@@H:3]([NH:12][C:13]1[CH:14]=[N:15][CH:16]=[C:17]([C:19]2[C:27]3[C:22](=[N:23][CH:24]=[C:25]([CH2:28][O:29][CH2:30][CH2:31][N:32]4[CH2:36][CH2:35][CH2:34][CH2:33]4)[CH:26]=3)[N:21](COCC[Si](C)(C)C)[CH:20]=2)[CH:18]=1)[C:4]([NH:6][CH2:7][C:8]([F:11])([F:10])[F:9])=[O:5].[F-].[Cs+]>CS(C)=O>[CH3:1][CH:2]([CH3:45])[C@@H:3]([NH:12][C:13]1[CH:14]=[N:15][CH:16]=[C:17]([C:19]2[C:27]3[C:22](=[N:23][CH:24]=[C:25]([CH2:28][O:29][CH2:30][CH2:31][N:32]4[CH2:36][CH2:35][CH2:34][CH2:33]4)[CH:26]=3)[NH:21][CH:20]=2)[CH:18]=1)[C:4]([NH:6][CH2:7][C:8]([F:11])([F:10])[F:9])=[O:5]

Participants

Conditions

Temperature: 140 °C

Procedure

In a microwave vial containing (R)-3-methyl-2-(5-(5-((2-(pyrrolidin-1-yl)ethoxy)methyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-ylamino)-N-(2,2,2-trifluoroethyl)butanamide 9-1a (60.7 mg, 0.094 mmol), added DMSO (1 ml, 0.094M) followed by Cesium Fluoride (284 mg, 1.871 mmol). The reaction mixture was heated at 140° C. for one hour on an oil bath open to air. LC/MS indicated conversion to product, the reaction mixture was filtered through a fine filter funnel and purified on the Gilson HPLC instrument using acetonitrile: water with 0.1% TFA buffer system using 10-60% gradient to give the title compound 9-1 (3.32 mg, 5.61%). LRMS (ESI) m/z 519.3 [(M+H)+; calcd for C26H33F3N6O2: 519.3]

Workup

filtrationthe reaction mixture was filtered through a fine filter funnel
custompurified on the Gilson HPLC instrument

Sources & evidence

ORD record: ord-6ff535de78f243d1af8a4da10ad5be0f
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09096598B2

Reaction notes

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