Potassium Carbonate → (2,5-Dichloropyrimidin-4-yl)-(2-methoxy-4-morpholin-4-yl-phenyl)-amine

HRID 1687205Notes

Reaction equation

HRID 1687205 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([Cl:9])=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:16][O:17][C:18]1[CH:23]=[C:22]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[CH:21]=[CH:20][C:19]=1[NH2:30]>O1CCCC1>[Cl:1][C:2]1[N:7]=[C:6]([NH:30][C:19]2[CH:20]=[CH:21][C:22]([N:24]3[CH2:25][CH2:26][O:27][CH2:28][CH2:29]3)=[CH:23][C:18]=2[O:17][CH3:16])[C:5]([Cl:9])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 2372592,4,5-TrichloropyrimidineHCID 4149602-Methoxy-4-morpholinoaniline

Product 1

HCID 86633851(2,5-Dichloropyrimidin-4-yl)-(2-methoxy-4-morpholin-4-yl-phenyl)-amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2,4,5-Trichloropyrimidine (978 mg, 5.33 mmol) was dissolved in Tetrahydrofuran (30 mL), then Potassium carbonate (1.52 g, 11.0 mmol) was added. 2-Methoxy-4-morpholin-4-yl-phenylamine (1.030 g, 4.95 mmol) was added, and the reaction was stirred under an atmosphere of Nitrogen, overnight. The reaction was partitioned between 30 mL water, 30 mL dichloromethane and separated. The aq. layer was extracted once with 30 mL dichloromethane, the combined organics washed once with 50 mL brine, then dried over sodium sulfate. The contents were concentrated onto silica gel, and chromatographed on an ISCO cartridge (120 g SiO2, 0-40% EA:Hex). (2,5-Dichloro-pyrimidin-4-yl)-(2-methoxy-4-morpholin-4-yl-phenyl)-amine was isolated as a yellow solid (1.40 g, 80%). m.p.=156-160° C.; LCMS (m/e)=355 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 8.30 (d, 1H, J=8.8 Hz), 8.13 (s, 1H), 7.87 (s, 1H), 6.57 (d, 1H, J=8.8 Hz), 6.52 (s, 1H), 3.93 (s, 3H), 3.88 (t, 4H, J=4.8 Hz), 3.16 (t, 4H, J=4.8 Hz).

Workup

  1. customThe reaction was partitioned between 30 mL water, 30 mL dichloromethane
  2. customseparated
  3. extractionThe aq. layer was extracted once with 30 mL dichloromethane
  4. washthe combined organics washed once with 50 mL brine
  5. dry with materialdried over sodium sulfate
  6. concentrationThe contents were concentrated onto silica gel
  7. customchromatographed on an ISCO cartridge (120 g SiO2, 0-40% EA:Hex)

Sources & evidence

ORD record
ord-ebd4b42145af4f818c6ba94cfe37ba39
Source dataset
uspto-grants-2012_04
Patent number
US08148391B2

Reaction notes

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