Hydrochloric Acid → HCID 86711770, compound

HRID 528497Notes

Reaction equation

HRID 528497 reaction equation
C(O[C:6](=O)[N:7]([CH2:9][CH2:10][O:11][C:12]1[C:13](Cl)=[N:14][C:15]([Cl:24])=[N:16][C:17]=1[N:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1)C)(C)(C)C.Cl>CO>[Cl:24][C:15]1[N:16]=[C:17]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[C:12]2[O:11][CH2:10][CH2:9][N:7]([CH3:6])[C:13]=2[N:14]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 86711769HCID 86711769, compound

Product 1

HCID 86711770HCID 86711770, compoundYield 91%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of [2-(2,4-dichloro-6-morpholin-4-yl-pyrimidin-5-yloxy)-ethyl]-methyl-carbamic acid tert-butyl ester (1.50 mmol) and 4M HCl in methanol (10 mL) was stirred at RT for 1.5 hours then concentrated in vacuo and azeotroped with ethanol. The resultant residue was dissolved in methanol (10 mL) then treated with triethylamine (3.0 mL) and the mixture stirred at RT for 30 minutes before being concentrated in vacuo. The resulting residue was purified by column chromatography (SiO2, gradient 0-50% ethyl acetate in cyclohexane) affording 2-Chloro-8-methyl-4-morpholin-4-yl-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazine (368 mg, 91% over 3 steps). LCMS: RT=2.94 min, [M+H]+=271/273.

Workup

  1. concentrationthen concentrated in vacuo
  2. customazeotroped with ethanol
  3. dissolutionThe resultant residue was dissolved in methanol (10 mL)
  4. additionthen treated with triethylamine (3.0 mL)
  5. stirringthe mixture stirred at RT for 30 minutes
  6. concentrationbefore being concentrated in vacuo
  7. customThe resulting residue was purified by column chromatography (SiO2, gradient 0-50% ethyl acetate in cyclohexane)

Sources & evidence

ORD record
ord-f653f9c587fa4734b099f66d55549f3a
Source dataset
uspto-grants-2016_05
Patent number
US09346817B2

Reaction notes

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