Diisopropylethylamine → N-(1-(5-chloro-2-methylphenyl)-3-methyl-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 1466562Notes

Reaction equation

HRID 1466562 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:15])=[C:6]([N:8]2[C:12]([NH2:13])=[CH:11][C:10]([CH3:14])=[N:9]2)[CH:7]=1.[N:16]1[N:20]2[CH:21]=[CH:22][CH:23]=[N:24][C:19]2=[C:18]([C:25](O)=[O:26])[CH:17]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C)C1C=CN=CC=1.CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:15])=[C:6]([N:8]2[C:12]([NH:13][C:25]([C:18]3[CH:17]=[N:16][N:20]4[CH:21]=[CH:22][CH:23]=[N:24][C:19]=34)=[O:26])=[CH:11][C:10]([CH3:14])=[N:9]2)[CH:7]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 1910189Pyrazolo[1,5-a]pyrimidine-3-carboxylic acidHCID 11038641((7-Azabenzotriazol-1-YL)oxy)tris(pyrrolidino)phosphonium hexafluorophosphateHCID 580631601-(5-chloro-2-methylphenyl)-3-methyl-1H-pyrazol-5-amine

Product 1

HCID 49856844N-(1-(5-chloro-2-methylphenyl)-3-methyl-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamideYield 31.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of 1-(5-chloro-2-methylphenyl)-3-methyl-1H-pyrazol-5-amine (95.3 mg, 0.430 mmol, 1 eq), pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (79.5 mg, 0.487 mmol, 1.13 eq), 7-azabenzotriazol-1-yloxy-tris-(pyrrolidino)phosphonium hexafluorophosphate (0.290 g, 0.558 mmol, 1.30 eq), N,N-diisopropylethylamine (0.2 mL, 1.1 mmol, 2.7 eq), and 4-dimethylaminopyridine (11.0 mg, 0.09 mmol, 0.21 eq) in 4.0 mL N,N-dimethylformamide was stirred at 75° C. for 3 days. The reaction mixture was partitioned between ethyl acetate and water, and the organic portion washed with brine, dried over magnesium sulfate, filtered through a silica gel plug, and concentrated. The crude product was purified by reverse phase HPLC and lyophilized to give 50.0 mg (30%) of N-(1-(5-chloro-2-methylphenyl)-3-methyl-1H-pyrazol-5-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide. LCMS (ESI) m+H=367.0; 1H NMR (400 MHz, DMSO-d6) δ: 10.03 (s, 1H), 9.32 (d, 1H), 8.68 (s, 1H), 8.36 (d, 1H), 7.60 (d, 1H), 7.58 (s, 1H), 7.55 (d, 1H), 7.27 (d of d, 1H), 6.53 (s, 1H), 2.24 (s, 3H), 2.05 (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. filtrationfiltered through a silica gel plug
  5. concentrationconcentrated
  6. customThe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-ef71a5fdec2c45adbe024e522be19292
Source dataset
uspto-grants-2015_04
Patent number
US08999998B2

Reaction notes

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