Potassium Phosphate, Tribasic → 1-[(2-Tert-butyl-6-cyclopropylpyrazolo[1,5-a]pyrimidin-3-yl)methyl]-4-propylpyrrolidin-2-one

HRID 1926799Notes

Reaction equation

HRID 1926799 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[C:9]([C:21]([CH3:24])([CH3:23])[CH3:22])[C:10]=2[CH2:11][N:12]2[CH2:16][CH:15]([CH2:17][CH2:18][CH3:19])[CH2:14][C:13]2=[O:20])[CH:7]=1.[CH:25]1(B(O)O)[CH2:27][CH2:26]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:21]([C:9]1[C:10]([CH2:11][N:12]2[CH2:16][CH:15]([CH2:17][CH2:18][CH3:19])[CH2:14][C:13]2=[O:20])=[C:5]2[N:4]=[CH:3][C:2]([CH:25]3[CH2:27][CH2:26]3)=[CH:7][N:6]2[N:8]=1)([CH3:24])([CH3:23])[CH3:22]

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 577430771-[(6-Bromo-2-tertbutylpyrazolo(1,5-a)pyrimidin-3-yl)methyl]-4-propylpyrrolidin-2-one

Product 1

HCID 536291231-[(2-Tert-butyl-6-cyclopropylpyrazolo[1,5-a]pyrimidin-3-yl)methyl]-4-propylpyrrolidin-2-oneYield 29.2%

Reagents, catalysts & solvents 3

HCID 178420534HCID 178420534, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 1-[(6-bromo-2-tertbutylpyrazolo(1,5-a)pyrimidin-3-yl)methyl]-4-propylpyrrolidin-2-one 190 (0.56 mmol, 1 eq, 0.2 g) in 5 ml of DME is added successively palladium-tetrakis-triphenylphosphine (0.019 mmol, 0.03 eq, 22 mg), cyclopropyl-boronic acid (0.727 mmol, 1.1 eq, 62 mg), and K3PO4 (1.98 mmol, 3 eq, 0.42 g) dissolved in 4 ml of water. The mixture is degassed and stirred vigorously at 90° C. for 4 hours. The solvent is removed under reduce pressure, water is added and the resulting mixture is extracted with dichloromethane. The organic phases are combined, washed with brine and dried over MgSO4. Volatiles are removed under reduce pressure. The crude product is purified by chromatography on silicagel (CH2Cl2/MeOH/NH4OH: 99/1/0.1) to afford 58 mg of pure 1-[(2-tert-butyl-6-cyclopropylpyrazolo[1,5-a]pyrimidin-3-yl)methyl]-4-propylpyrrolidin-2-one 192 the compound in pure form.

Workup

  1. customThe mixture is degassed
  2. customThe solvent is removed
  3. additionis added
  4. extractionthe resulting mixture is extracted with dichloromethane
  5. washwashed with brine
  6. dry with materialdried over MgSO4
  7. customVolatiles are removed
  8. customThe crude product is purified by chromatography on silicagel (CH2Cl2/MeOH/NH4OH: 99/1/0.1)

Sources & evidence

ORD record
ord-f0b64359180e4c15b0c171ab7f89fd6a
Source dataset
uspto-grants-2012_05
Patent number
US08183241B2

Reaction notes

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