Methanol → [4-(5-Diethylaminomethyl-2,4-dimethyl-1H-pyrrol-3-yl)-pyrimidin-2-yl]-(4-fluoro-phenyl)-amine

HRID 855620Notes

Reaction equation

HRID 855620 reaction equation
[CH2:1]([NH:3][CH2:4][CH3:5])[CH3:2].[CH3:6][C:7]1[NH:8][CH:9]=[C:10]([CH3:26])[C:11]=1[C:12]1[CH:17]=[CH:16][N:15]=[C:14]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[N:13]=1.[CH3:27]O>C=O.O>[CH2:1]([N:3]([CH2:27][C:9]1[NH:8][C:7]([CH3:6])=[C:11]([C:12]2[CH:17]=[CH:16][N:15]=[C:14]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[N:13]=2)[C:10]=1[CH3:26])[CH2:4][CH3:5])[CH3:2]

Participants

6

Reactant 3

HCID 887MethanolHCID 8021DiethylamineHCID 9856973[4-(2,4-Dimethyl-1H-pyrrol-3-yl)-pyrimidin-2-yl]-(4-fluoro-phenyl)-amine

Product 1

HCID 69352385[4-(5-Diethylaminomethyl-2,4-dimethyl-1H-pyrrol-3-yl)-pyrimidin-2-yl]-(4-fluoro-phenyl)-amine

Reagents, catalysts & solvents 2

HCID 712FormaldehydeSolventHCID 962WaterSolvent

Procedure

Diethylamine (40 μL, 0.31 mmol) was diluted with methanol (0.5 mL) and formaldehyde (30 μL of a 37% w/w aq solution, 0.37 mmol) was added. [4-(2,4-Dimethyl-1H-pyrrol-3-yl)-pyrimidin-2-yl]-(4-fluoro-phenyl)-amine (87 mg, 0.31 mmol) was added in small portions and the mixture was heated to reflux. After 1.5 h the mixture was diluted with H2O (10 mL). The resulting precipitate was filtered and triturated in 2 M aq HCl. The mixture was filtered and the filtrate was washed with 2 M aq NaOH. The filtrate was extracted with EtOAc (3×15 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 (36 mg) as an orange solid after recrystallisation from iPr2O. M.p. 71.9–74.2° C. MS: [M+H]+=367.7 (C21H26FN5 requires 367.5). 1H-NMR (CD3OD) δ: 1.10 (t, 6H, J=7.1 Hz, CH3), 2.19 (s, 3H, CH3), 2.41 (s, 3H, CH3), 2.58 (t, 4H, J=7.8 Hz, CH2), 3.56 (s, 2H, CH2), 6.78 (d, 1H, J=5.6 Hz, pyrimidinyl-H), 7.00 (t, 2H, J=8.5 Hz, Ph-H), 7.61–7.63 (m, 2H, Ph-H), 8.22 (d, 1H, J=5.4 Hz, pyrimidinyl-H).

Workup

  1. additionwas added
  2. temperaturethe mixture was heated to reflux
  3. filtrationThe resulting precipitate was filtered
  4. customtriturated in 2 M aq HCl
  5. filtrationThe mixture was filtered
  6. washthe filtrate was washed with 2 M aq NaOH
  7. extractionThe filtrate was extracted with EtOAc (3×15 mL)
  8. washThe combined organic extracts were washed (brine)
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. customevaporated in vacuo
  12. customThe crude product was purified by SiO2 chromatography (heptane/EtOAc gradient elution)

Sources & evidence

ORD record
ord-217f0290b21d437281eae08326ccd556
Source dataset
uspto-grants-2007_08
Patent number
US07262202B2

Reaction notes

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