7-Chloro-2-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-5-amine → Methyl 4-(7-chloro-2-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-5-ylcarbamoyl)benzoate

HRID 1409184Notes

Reaction equation

HRID 1409184 reaction equation
[Cl:1][C:2]1[N:7]2[N:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=[C:6]2[N:5]=[C:4]([NH2:15])[CH:3]=1.[Cl-].[CH3:17][O:18][C:19](=[O:29])[C:20]1[CH:28]=[CH:27][C:23]([C:24](O)=[O:25])=[CH:22][CH:21]=1>N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[Cl:1][C:2]1[N:7]2[N:8]=[C:9]([C:11]([F:12])([F:13])[F:14])[CH:10]=[C:6]2[N:5]=[C:4]([NH:15][C:24]([C:23]2[CH:27]=[CH:28][C:20]([C:19]([O:18][CH3:17])=[O:29])=[CH:21][CH:22]=2)=[O:25])[CH:3]=1

Participants

5

Reactant 2

HCID 442513097-Chloro-2-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-5-amineHCID 53442854Terephthalic acid monomethylester chloride

Product 1

HCID 86652275Methyl 4-(7-chloro-2-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-5-ylcarbamoyl)benzoateYield 10%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent2×

Conditions

Temperature
0 °C

Procedure

7-chloro-2-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-5-amine (0.5 g, 1.0 equivalent) was suspended in pyridine (0.2 M) in a round bottom flask. At 0° C. was added a solution of terephthalic acid monomethylester chloride (2.0 equivalents) pre-dissolved in pyridine (0.8M), and followed by addition of N,N-dimethylpyridin-4-amine (0.1 equivalent). The mixture was stirred vigorously at 0° C. for 48 h. The reaction was quenched with saturated NaHCO3; pyridine was removed in vacuo and the residue was extracted with EtOAc twice and the combined organic layers were dried over Na2SO4. The organic layers were concentrated in vacuo and the crude mixture was purified using chromatography (SiO2, gradient of 10 to 50% EtOAc/hexanes) to afford the titled compound (10%) as a solid. Melting point (191.0-195.0° C.). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.90 (s, 3H) 7.20 (s, 1H) 8.06-8.11 (m, 2H) 8.12-8.18 (m, 2H) 8.32 (s, 1H) 11.88 (s, 1H); ESI-MS: m/z 399.0 (M+H)+.

Workup

  1. customThe reaction was quenched with saturated NaHCO3
  2. custompyridine was removed in vacuo
  3. extractionthe residue was extracted with EtOAc twice
  4. dry with materialthe combined organic layers were dried over Na2SO4
  5. concentrationThe organic layers were concentrated in vacuo
  6. customthe crude mixture was purified

Sources & evidence

ORD record
ord-64f85fe5104145589995e434430f9124
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

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