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

HRID 855619Notes

Reaction equation

HRID 855619 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.[Cl:22]N1C(=O)CCC1=O>C1COCC1>[Cl: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 31398ChlorosuccinimideHCID 9856973[4-(2,4-Dimethyl-1H-pyrrol-3-yl)-pyrimidin-2-yl]-(4-fluoro-phenyl)-amine

Product 1

HCID 65393154-(5-chloro-2,4-dimethyl-1H-pyrrol-3-yl)-N-(4-fluorophenyl)pyrimidin-2-amineYield 41.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-60 °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 −60° C. N-Chlorosuccinimide (41 mg, 0.31 mmol) was dissolved in THF (2 mL) and added dropwise, keeping the internal temperature ≦−50° C. The mixture was stirred for 30 min with cooling then evaporated in vacuo. The residue was treated with H2O (10 mL) and extracted with EtOAc (3×10 mL). The combined organic extracts 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 (37 mg) as an orange solid after recrystallisation from iPr2O. M.p. 200–203° C. MS: [M+H]+=317.7 (C16H14ClFN4 requires 316.8). 1H-NMR (CDCl3) δ: 2.17 (s, 3H, CH3), 2.42 (s, 3H, CH3) 6.77 (d, 1H, J=5.9 Hz, pyrimidinyl-H), 7.02–7.06 (m, 3H, Ph-h, NH), 7.54–7.56 (m, 2H, Ph-H), 7.95 (br. s, 1H, NH), 8.25 (d, 1H, J=5.4 Hz, pyrimidinyl-H).

Workup

  1. additionadded dropwise
  2. customthe internal temperature ≦−50° 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 extracts 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-9ab46bcdb4a2448ea2f8d6a6881ad484
Source dataset
uspto-grants-2007_08
Patent number
US07262202B2

Reaction notes

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