N-bromobutanimide → 4-(5-bromo-2,4-dimethyl-1H-pyrrol-3-yl)-N-(4-fluorophenyl)pyrimidin-2-amine

HRID 855618Notes

Reaction equation

HRID 855618 reaction equation
[CH3:1][C:2]1[NH:3][CH:4]=[C:5]([CH3:21])[C:6]=1[C:7]1[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[N:8]=1.[Br:22]N1C(=O)CCC1=O>C1COCC1>[Br:22][C:4]1[NH:3][C:2]([CH3:1])=[C:6]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=3)[N:8]=2)[C:5]=1[CH3:21]

Participants

4

Reactant 2

HCID 67184N-bromobutanimideHCID 9856973[4-(2,4-Dimethyl-1H-pyrrol-3-yl)-pyrimidin-2-yl]-(4-fluoro-phenyl)-amine

Product 1

HCID 65393164-(5-bromo-2,4-dimethyl-1H-pyrrol-3-yl)-N-(4-fluorophenyl)pyrimidin-2-amineYield 18.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-50 °C

Procedure

[4-(2,4-Dimethyl-1H-pyrrol-3-yl)-pyrimidin-2-yl]-(4-fluoro-phenyl)-amine (80 mg, 0.28 mmol) was dissolved in THF (4 mL) and cooled to −50° C. N-Bromosuccinimide (55 mg, 0.31 mmol) was dissolved in THF (2 mL) and added dropwise, keeping the internal temperature ≦−40° C. The mixture was stirred for 1 h with cooling then evaporated in vacuo. The residue was treated with H2O (10 mL) and extracted with EtOAc (3×10 mL). The combined organic extractss were washed (brine), dried (MgSO4), filtered, and evaporated in vacuo. The crude product was purified by SiO2 chromatography heptane/EtOAc gradient elution) to afford the title compound (19 mg) as an orange solid after recrystallisation from iPr2O. M.p. 181.4–183.3° C. MS: [M+H]+=362.9 (C16H14BrFN4 requires 361.2). 1H-NMR (CDCl3) δ: 2.10 (s, 3H, CH3), 2.36 (s, 3H, CH3) 6.56 (d, 1H, J=5.1 Hz, pyrimidinyl-H), 6.97 (t, 2H, J=8.3 Hz, Ph-H), 7.00 (br. s, 1H, NH), 7.79–7.52 (m, 2H, Ph-H), 8.85 (br. s, 1H, NH), 8.26 (d, 1H, J=5.1 Hz, pyrimidinyl-H).

Workup

  1. additionadded dropwise
  2. customthe internal temperature ≦−40° C
  3. temperaturewith cooling
  4. customthen evaporated in vacuo
  5. additionThe residue was treated with H2O (10 mL)
  6. extractionextracted with EtOAc (3×10 mL)
  7. washThe combined organic extractss were washed (brine)
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. customThe crude product was purified by SiO2 chromatography heptane/EtOAc gradient elution)

Sources & evidence

ORD record
ord-55d2756c423144a697d063ee7598f84c
Source dataset
uspto-grants-2007_08
Patent number
US07262202B2

Reaction notes

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