tert-Butanol → HCID 178470456, compound

HRID 1049151Notes

Reaction equation

HRID 1049151 reaction equation
C(O)(C)(C)C.[F-].[Cs+].Br[C:9]1[C:10]([C:38]([O:40][CH2:41][CH3:42])=[O:39])=[N:11][N:12]([C:14]2([CH2:35][C:36]#[N:37])[CH2:17][N:16]([C:18]3[CH:23]=[C:22]([F:24])[C:21]([C:25]([NH:27][C@@H:28]([CH3:33])[C:29]([F:32])([F:31])[F:30])=[O:26])=[CH:20][C:19]=3[F:34])[CH2:15]2)[CH:13]=1.[CH3:43][C:44]1[C:48](B2OC(C)(C)C(C)(C)O2)=[CH:47][NH:46][N:45]=1>O.C(OCC)(=O)C>[C:36]([CH2:35][C:14]1([N:12]2[CH:13]=[C:9]([C:48]3[C:44]([CH3:43])=[N:45][NH:46][CH:47]=3)[C:10]([C:38]([O:40][CH2:41][CH3:42])=[O:39])=[N:11]2)[CH2:17][N:16]([C:18]2[CH:23]=[C:22]([F:24])[C:21]([C:25]([NH:27][C@@H:28]([CH3:33])[C:29]([F:32])([F:31])[F:30])=[O:26])=[CH:20][C:19]=2[F:34])[CH2:15]1)#[N:37]

Participants

7

Reactant 4

HCID 6386tert-ButanolHCID 25953Cesium fluorideHCID 117699944Ethyl 4-bromo-1-{3-(cyanomethyl)-1-[2,5-difluoro-4-({[(1S)-2,2,2-trifluoro-1-methylethyl]amino}carbonyl)phenyl]azetidin-3-yl}-1H-pyrazole-3-carboxylateHCID 178434487HCID 178434487, compound

Product 1

HCID 178470456HCID 178470456, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

To a microwave vial were charged with tert-butyl alcohol (1.2 mL), and water (1.2 mL), cesium fluoride (683 mg, 4.50 mmol), ethyl 4-bromo-1-{3-(cyanomethyl)-1-[2,5-difluoro-4-({[(1S)-2,2,2-trifluoro-1-methylethyl]amino}carbonyl)phenyl]azetidin-3-yl}-1H-pyrazole-3-carboxylate (725 mg, 1.28 mmol) and 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (401 mg, 1.93 mmol), followed by Pd-127 (49 mg, 0.064 mmol) (from Johnson Mathew). The reaction mixture was heated at 85° C. for 48 h. The reaction was cooled to room temperature, diluted with water and ethyl acetate. The aqueous layer was extracted with ethyl acetate. The organic layer was dried over Na2SO4, concentrated. The resulting residue was purified with flash chromatography (eluting with 30-100% ethyl acetate in hexanes) to give the desired product as an oil. LCMS calculated for C25H25F5N7O3 (M+H)+: m/z=566.2. Found: 566.0.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated
  5. customThe resulting residue was purified with flash chromatography (eluting with 30-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-1962570e09ba46bcad77b4d382083204
Source dataset
uspto-grants-2016_07
Patent number
US09382231B2

Reaction notes

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