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

HRID 855616Notes

Reaction equation

HRID 855616 reaction equation
[N+:1]([O-:4])(O)=[O:2].[F:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:13]([NH2:15])=[NH:14])=[CH:8][CH:7]=1.C([O-])([O-])=O.[K+].[K+].CO[CH2:24][CH2:25]O>>[CH3:10][C:9]1[NH:12][C:13]([N+:1]([O-:4])=[O:2])=[C:24]([CH3:25])[C:8]=1[C:7]1[CH:6]=[CH:11][N:15]=[C:13]([NH:12][C:9]2[CH:8]=[CH:7][C:6]([F:5])=[CH:11][CH:10]=2)[N:14]=1

Participants

4

Reactant 3

HCID 80192-MethoxyethanolHCID 11430Potassium CarbonateHCID 1785125564-Fluorophenylguanidine nitrate

Product 1

HCID 65393144-(2,4-dimethyl-5-nitro-1H-pyrrol-3-yl)-N-(4-fluorophenyl)pyrimidin-2-amine

Conditions

Temperature
120 °C

Procedure

3-Dimethylamino-1-(2,4-dimethyl-5-nitro-1H-pyrrol-3-yl)-propenone (110 mg, 0.46 mmol), 4-fluorophenyl guanidine nitrate (150 mg, 0.7 mmol), and K2CO3 (193 mg, 1.4 mmol) were partially dissolved in 2-methoxyethanol and heated at 120° C. for 18 h. The mixture was concentrated in vacuo and purified by SiO2 chromatography (heptane/EtOAc gradient elution). The crude product was triturated in iPr2O to afford the title compound (22 mg) as a pale orange solid. M.p. 166.3–170.1° C. MS: [M+H]+=329.3 (C16H14FN5O2 requires 327.3). 1H-NMR (DMSO-d6) δ: 2.49 (s, 3H, CH3), 2.59 (s, 3H, CH3), 6.73 (d, 1H, J=5.1 Hz, pyrimidinyl-H), 7.04 (t, 2H, J=8.8 Hz, Ph-H), 7.07 (br. s, 1H, NH), 7.55–7.58 (m, 2H, Ph-H), 8.44 (d, 1H, J=5.1 Hz, pyrimidinyl-H), 9.40 (br. s, 1H, NH).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. custompurified by SiO2 chromatography (heptane/EtOAc gradient elution)
  3. customThe crude product was triturated in iPr2O

Sources & evidence

ORD record
ord-7341095d0cb74d4f977aed5fd5129627
Source dataset
uspto-grants-2007_08
Patent number
US07262202B2

Reaction notes

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