Diisopropylethylamine → N-(4-bromo-1-methyl-1H-pyrazol-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 1466574Notes

Reaction equation

HRID 1466574 reaction equation
[N:1]1[N:5]2[CH:6]=[CH:7][CH:8]=[N:9][C:4]2=[C:3]([C:10]([OH:12])=O)[CH:2]=1.[Br:13][C:14]1[C:15]([NH2:20])=[N:16][N:17]([CH3:19])[CH:18]=1.C(N(CC)C(C)C)(C)C>CN(C)C1C=CN=CC=1.CN(C)C=O>[Br:13][C:14]1[C:15]([NH:20][C:10]([C:3]2[CH:2]=[N:1][N:5]3[CH:6]=[CH:7][CH:8]=[N:9][C:4]=23)=[O:12])=[N:16][N:17]([CH3:19])[CH:18]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 1910189Pyrazolo[1,5-a]pyrimidine-3-carboxylic acidHCID 27352834-bromo-1-methyl-1H-pyrazol-3-amine

Product 1

HCID 66851236N-(4-bromo-1-methyl-1H-pyrazol-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamideYield 63%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (165.5 mg, 1.014 mmol, 1.01 eq), 4-bromo-1-methyl-1H-pyrazol-3-amine (177.4 mg, 1.008 mmol, 1.0 eq), N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uranium hexafluorophosphate (497 mg, 1.31 mmol, 1.30 eq), N,N-diisopropylethylamine (0.25 mL, 1.4 mmol, 1.4 eq), and 4-dimethylaminopyridine (33.8 mg, 0.277 mmol, 0.27 eq) in 5 mL N,N-dimethylformamide was heated at 50° C. for 4 days. The reaction mixture was partitioned between ethyl acetate and water, and the organic portion washed with brine, dried over magnesium sulfate and concentrated. The crude product was purified by flash chromatography on silica gel (20 to 80% ethyl acetate in dichloromethane (containing 5% methanol)) to yield 203.6 mg (63%) of N-(4-bromo-1-methyl-1H-pyrazol-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide. LCMS (ESI) m+H=321.1; 1H NMR (400 MHz, CD3OD) δ: 9.16 (d, 1H), 8.84 (d, 1H), 8.68 (s, 1H), 7.76 (s, 1H), 7.28 (d of d, 1H), 3.88 (s, 3H).

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and water
  2. washthe organic portion washed with brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customThe crude product was purified by flash chromatography on silica gel (20 to 80% ethyl acetate in dichloromethane (containing 5% methanol))

Sources & evidence

ORD record
ord-edeb9c13b5494389a32a4d59069883f2
Source dataset
uspto-grants-2015_04
Patent number
US08999998B2

Reaction notes

Loading…