Methylamine → 2-Chloro-8-methyl-4-morpholin-4-yl-8H-pyrimido[5,4-b][1,4]oxazin-7-one

HRID 528499Notes

Reaction equation

HRID 528499 reaction equation
C(O[C:4](=[O:21])[CH2:5][O:6][C:7]1[C:8](Cl)=[N:9][C:10]([Cl:19])=[N:11][C:12]=1[N:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1)C.CN.[CH2:24]([N:26](CC)CC)C>>[Cl:19][C:10]1[N:11]=[C:12]([N:13]2[CH2:14][CH2:15][O:16][CH2:17][CH2:18]2)[C:7]2[O:6][CH2:5][C:4](=[O:21])[N:26]([CH3:24])[C:8]=2[N:9]=1

Participants

4

Reactant 3

HCID 6329MethylamineHCID 8471TriethylamineHCID 86711735(2,4-Dichloro-6-morpholin-4-yl-pyrimidin-5-yloxy)-acetic acid ethyl ester

Product 1

HCID 867117722-Chloro-8-methyl-4-morpholin-4-yl-8H-pyrimido[5,4-b][1,4]oxazin-7-oneYield 38%

Conditions

Temperature
140 °C

Procedure

A mixture of (2,4-dichloro-6-morpholin-4-yl-pyrimidin-5-yloxy)-acetic acid ethyl ester (501 mg, 1.49 mmol), methylamine (1.0 mL, 2.0 mmol, 2 M in THF) and triethylamine (250 μL, 1.79 mmol) in IMS (10 mL) was heated at 140° C. for 35 minutes using microwave irradiation. The reaction mixture was concentrated in vacuo and the resulting residue purified by column chromatography (SiO2, 0-20% ethyl acetate in cyclohexane) affording 2-Chloro-8-methyl-4-morpholin-4-yl-8H-pyrimido[5,4-b][1,4]oxazin-7-one (159 mg, 38%). LCMS: RT=2.93 min, [M+H]+=285/287.

Workup

  1. custommicrowave irradiation
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customthe resulting residue purified by column chromatography (SiO2, 0-20% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-cb0e528c14f34d7eb4e66f8b8274b2b3
Source dataset
uspto-grants-2016_05
Patent number
US09346817B2

Reaction notes

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