Phosphorus oxychloride → HCID 136163955, compound

HRID 390357Notes

Reaction equation

HRID 390357 reaction equation
C([O:8][C:9]1[C:18](=[O:19])[N:17]2[C:12]([C:13]([CH3:21])([CH3:20])[O:14][CH2:15][CH2:16]2)=[N:11][C:10]=1[C:22]([NH:24][CH2:25][C:26](=O)[CH2:27][C:28]1[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=1)=[O:23])C1C=CC=CC=1.O=P(Cl)(Cl)Cl>C1(C)C=CC=CC=1>[F:34][C:31]1[CH:32]=[CH:33][C:28]([CH2:27][C:26]2[O:23][C:22]([C:10]3[N:11]=[C:12]4[N:17]([C:18](=[O:19])[C:9]=3[OH:8])[CH2:16][CH2:15][O:14][C:13]4([CH3:21])[CH3:20])=[N:24][CH:25]=2)=[CH:29][CH:30]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 58458928HCID 58458928, compound

Product 1

HCID 136163955HCID 136163955, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of 3-(benzyloxy)-N-(3-(4-fluorophenyl)-2-oxopropyl)-9,9-dimethyl-4-oxo-4,6,7,9-tetrahydropyrimido[2,1-c][1,4]oxazine-2-carboxamide (0.16 g, 0.3337 mmol) and POCl3 (2 mL) in toluene (15 mL) was heated at reflux for 5 h, then cooled, concentrated and the resulting residue taken up in EtOAc (50 mL), washed with water (2×10 mL), brine (10 mL), dried (Na2SO4), filtered and concentrated to give a yellow residue. Purification by preparative HPLC on C18 column using water/MeOH containing 0.1% TFA provided the title as a white solid which was crystallized from MeOH/H2O to afford colorless needles. 1HNMR (500 MHz, CDCl3) δ: 11.04-10.92 (1H, br s), 7.26 (2H, dd, J=8.6, 5.5 Hz), 7.04 (2H, t, J=8.6 Hz), 6.86 (1H, s), 4.10 (2H, s), 4.07-4.02 (4H, m), 1.65 (6H, s). HRMS (M+H) calcd for C19H19N3O4F: 372.1360. found: 372.1356. Anal calcd for C19H18N3O4F: C, 61.45; H, 4.88; N, 11.31. found: C, 61.19; H, 4.74; N, 11.14.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 5 h
  3. temperaturecooled
  4. concentrationconcentrated
  5. washwashed with water (2×10 mL), brine (10 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a yellow residue
  10. customPurification by preparative HPLC on C18 column
  11. customprovided the title as a white solid which
  12. customwas crystallized from MeOH/H2O
  13. customto afford colorless needles

Sources & evidence

ORD record
ord-ddec5b111d8b4e29be085cabe677051f
Source dataset
uspto-grants-2013_02
Patent number
US08383639B2

Reaction notes

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