Pyridine → N-(2-methyl-7-morpholinopyrazolo[1,5-a]pyrimidin-5-yl)-4-(trifluoromethoxy)benzamide

HRID 1256422Notes

Reaction equation

HRID 1256422 reaction equation
Br[C:2]1[CH:25]=[CH:24][C:5]([C:6]([NH:8][C:9]2[CH:14]=[C:13]([N:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)[N:12]3[N:21]=[CH:22][CH:23]=[C:11]3[N:10]=2)=[O:7])=[CH:4][CH:3]=1.N1C=CC=C[CH:27]=1.[F:32][C:33]([F:45])([F:44])[O:34]C1C=CC(C(Cl)=O)=CC=1>>[CH3:27][C:22]1[CH:23]=[C:11]2[N:10]=[C:9]([NH:8][C:6](=[O:7])[C:5]3[CH:24]=[CH:25][C:2]([O:34][C:33]([F:45])([F:44])[F:32])=[CH:3][CH:4]=3)[CH:14]=[C:13]([N:15]3[CH2:20][CH2:19][O:18][CH2:17][CH2:16]3)[N:12]2[N:21]=1

Participants

4

Reactant 3

HCID 1049PyridineHCID 1421104-(Trifluoromethoxy)benzoyl ChlorideHCID 670644084-bromo-N-(7-morpholinopyrazolo[1,5-a]pyrimidin-5-yl)benzamide

Product 1

HCID 67064576N-(2-methyl-7-morpholinopyrazolo[1,5-a]pyrimidin-5-yl)-4-(trifluoromethoxy)benzamideYield 69.2%

Conditions

Temperature
0 °C

Procedure

A suspension of 2-methyl-7-morpholinopyrazolo[1,5-a]pyrimidin-5-amine (9B, 52 mg, 0.151 mmol) and pyridine (60 mg, 0.467 mmol) was cooled to 0° C. and treated with 4-trifluoromethoxybenzoyl chloride (78 mg, 0.395 mmol). After stirring for 30 min, the reaction was quenched by the addition of saturated aqueous sodium bicarbonate (5 mL). The aqueous mixture was extracted with ethyl acetate and the combined organics dried over sodium sulfate, filtered, and concentrated in vacuo. The crude material was dissolved in DMF/DMSO, filtered, and purified via preparative HPLC (60-80% MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a yellow solid (44.0 mg, 41%). Melting point (226.2-226.3° C.). 1H NMR (DMSO-d6) δ: 11.10 (s, 1H), 8.01-8.27 (m, 2H), 7.51 (dd, J=9.0, 0.9 Hz, 2H), 7.30 (s, 1H), 6.18 (s, 1H), 3.79-3.91 (m, 4H), 3.69-3.75 (m, 4H), 2.38 (s, 3H); ESI-MS: m/z 422.1 (M+H)+. Melting point (226.2-226.3° C.).

Workup

  1. customthe reaction was quenched by the addition of saturated aqueous sodium bicarbonate (5 mL)
  2. extractionThe aqueous mixture was extracted with ethyl acetate
  3. dry with materialthe combined organics dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe crude material was dissolved in DMF/DMSO
  7. filtrationfiltered
  8. custompurified via preparative HPLC (60-80% MeCN/H2O gradient+0.01% TFA)

Sources & evidence

ORD record
ord-fda7b905a65647b297474917a1256744
Source dataset
uspto-grants-2013_06
Patent number
US08461163B2

Reaction notes

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