Potassium Carbonate → tert-butyl 4-(8-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-fluoroquinolin-3-yl)-7-methyl-5H-pyrazolo[1,5-a]pyrrolo[2,3-d]pyrimidin-5-yl)piperidine-1-carboxylate

HRID 1423325Notes

Reaction equation

HRID 1423325 reaction equation
[CH2:1]([N:4]([C:18]1[C:23](Br)=[C:22]([N:25]([CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:40])[CH3:39])[CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[N:21]2[N:42]=[CH:43][C:44]([C:45]3[CH:46]=[N:47][C:48]4[C:53]([CH:54]=3)=[CH:52][C:51]([F:55])=[CH:50][CH:49]=4)=[C:20]2[N:19]=1)[CH:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]1)[CH:2]=[CH2:3].C([O-])([O-])=O.[K+].[K+]>[N+](CCCC)(CCCC)(CCCC)CCCC.[Br-].CN(C=O)C.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:31][Si:30]([CH3:32])([CH3:33])[CH2:29][CH2:28][O:27][CH2:26][N:25]([CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:39])[CH3:40])[C:22]1[N:21]2[N:42]=[CH:43][C:44]([C:45]3[CH:46]=[N:47][C:48]4[C:53]([CH:54]=3)=[CH:52][C:51]([F:55])=[CH:50][CH:49]=4)=[C:20]2[N:19]=[C:18]2[N:4]([CH:5]3[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:16])([CH3:15])[CH3:17])=[O:12])[CH2:7][CH2:6]3)[CH:1]=[C:2]([CH3:3])[C:23]=12

Participants

7

Reactant 2

HCID 11430Potassium CarbonateHCID 66980187HCID 66980187, compound

Product 1

HCID 66980243tert-butyl 4-(8-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-fluoroquinolin-3-yl)-7-methyl-5H-pyrazolo[1,5-a]pyrrolo[2,3-d]pyrimidin-5-yl)piperidine-1-carboxylate

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A degassed mixture of tert-butyl 4-(allyl(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-6-bromo-3-(6-fluoroquinolin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)amino)piperidine-1-carboxylate (163 mg, 0.19 mmol), Pd(OAc)2 (4.3 mg, 0.02 mmol), Bu4NBr (73.6 mg, 0.23 mmol), and K2CO3 (78.7 mg, 0.57 mmol) in DMF (6 mL) was heated at 90° C. for 3 h. After cooling to room temperature, the mixture was diluted with H2O and then extracted with ethyl acetate (×2). The combined organic layers were washed with brine and dried with Na2SO4. Evaporation and purification by column chromatography afforded tert-butyl 4-(8-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-fluoroquinolin-3-yl)-7-methyl-5H-pyrazolo[1,5-a]pyrrolo[2,3-d]pyrimidin-5-yl)piperidine-1-carboxylate: LCMS tR=1.96 Min (5 min run, UV254nm), Mass calculated for M+775.4, observed LC/MS m/z 776.0 (M+H).

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with ethyl acetate (×2)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried with Na2SO4
  5. customEvaporation and purification by column chromatography

Sources & evidence

ORD record
ord-cbe1de17ef1d4f398bf84f5ae4193ec7
Source dataset
uspto-grants-2015_01
Patent number
US08927562B2

Reaction notes

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