Pivalic acid → N-(3-bromo-5-methylphenyl)-4-cyclopropyl-2-pyrimidinamine

HRID 530372Notes

Reaction equation

HRID 530372 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH:8]2[CH2:10][CH2:9]2)[CH:5]=[CH:4][N:3]=1.[Br:11][C:12]1[CH:13]=[C:14]([CH:16]=[C:17]([CH3:19])[CH:18]=1)[NH2:15].C(O)(=O)C(C)(C)C>O1CCOCC1>[Br:11][C:12]1[CH:13]=[C:14]([NH:15][C:2]2[N:7]=[C:6]([CH:8]3[CH2:10][CH2:9]3)[CH:5]=[CH:4][N:3]=2)[CH:16]=[C:17]([CH3:19])[CH:18]=1

Participants

5

Reactant 3

HCID 6417Pivalic acidHCID 30185263-Bromo-5-methylanilineHCID 249019152-Chloro-4-cyclopropylpyrimidine

Product 1

HCID 118103319N-(3-bromo-5-methylphenyl)-4-cyclopropyl-2-pyrimidinamine

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of 2-chloro-4-cyclopropyl-pyrimidine (12.5 g, 81 mmol) and 3-bromo-5-methylaniline (18.1 g, 97 mmol) in 1,4-dioxane (100 mL) was added pivalic acid (9.3 mL, 81 mmol). The resulting mixture was heated to reflux and left stirring for 10 hours. The mixture was allowed to cool to room temperature and hexanes were added (80 mL). The slurry was filtered and the filtrate was washed with MeOH to afford a portion of N-(3-bromo-5-methylphenyl)-4-cyclopropylpyrimidin-2-amine. The mother liquors were concentrated, absorbed on silica gel and purified by silica gel column chromatography (EtOAc/Hex) to afford additional N-(3-bromo-5-methylphenyl)-4-cyclopropylpyrimidin-2-amine as a white solid. MS ESI calcd. for C14H15BrN3 [M+H]+ 304 and 306. found 304 and 306.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux
  3. waitleft
  4. filtrationThe slurry was filtered
  5. washthe filtrate was washed with MeOH

Sources & evidence

ORD record
ord-5fc3254820144d2aac13178f46a65b55
Source dataset
uspto-grants-2016_05
Patent number
US09353066B2

Reaction notes

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