Dichloromethane → Tert-butyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylate

HRID 1913250Notes

Reaction equation

HRID 1913250 reaction equation
[CH3:1][Si:2]([CH3:40])([CH3:39])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:8]1[N:13]2[N:14]=[CH:15][C:16](I)=[C:12]2[N:11]=[C:10]([CH:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)[CH:9]=1.[C:41]1([C:47]2[CH:52]=[CH:51][C:50](B3OC(C)(C)C(C)(C)O3)=[CH:49][N:48]=2)[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.ClCCl.C([O-])([O-])=O.[K+].[K+]>O.COCCOC>[CH3:1][Si:2]([CH3:40])([CH3:39])[CH2:3][CH2:4][O:5][CH2:6][N:7]([CH2:31][O:32][CH2:33][CH2:34][Si:35]([CH3:38])([CH3:37])[CH3:36])[C:8]1[N:13]2[N:14]=[CH:15][C:16]([C:50]3[CH:49]=[N:48][C:47]([C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=4)=[CH:52][CH:51]=3)=[C:12]2[N:11]=[C:10]([CH:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)[CH:9]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 457865262-Phenyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 66584511Tert-butyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylate

Product 1

HCID 66584899Tert-butyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-phenylpyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylateYield 57%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a pressure tube were charged tert-butyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-iodopyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylate (Int-9g, 1.7 g, 2.4 mmol), 2-phenyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (800 mg, 2.8 mmol), [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (100 mg, 0.12 mmol), K2CO3 (666 mg, 4.8 mmol), DME (10 mL) and water (5 mL). The tube was degassed with Ar briefly, capped and heated at 100° C. with stirring overnight. After cooling, the reaction mixture was diluted with EtOAc and water, the organic layer was isolated, washed with brine and dried (MgSO4). After the solvent was removed under reduced pressure, the residue was purified on silica. Elution with EtOAc in hexanes (0-50%) gave tert-butyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-phenyl pyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxy late (Int-9h) (1 g, 57%). LC/MS: m/z=731 (M+H+).

Workup

  1. customThe tube was degassed with Ar briefly
  2. customcapped
  3. temperatureAfter cooling
  4. additionthe reaction mixture was diluted with EtOAc and water
  5. customthe organic layer was isolated
  6. washwashed with brine
  7. dry with materialdried (MgSO4)
  8. customAfter the solvent was removed under reduced pressure
  9. customthe residue was purified on silica
  10. washElution with EtOAc in hexanes (0-50%)

Sources & evidence

ORD record
ord-0cd6017916244d6fa48e064a75b4b600
Source dataset
uspto-grants-2013_12
Patent number
US08609675B2

Reaction notes

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