Phosphorus oxychloride → HCID 86686095, compound

HRID 2400433Notes

Reaction equation

HRID 2400433 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[N:8][N:9]([C:11]2[NH:20][C:19](=O)[C:18]3[C:13](=[CH:14][C:15]([F:31])=[C:16]([O:22][C:23]4[C:28]([CH3:29])=[CH:27][CH:26]=[CH:25][C:24]=4[CH3:30])[CH:17]=3)[N:12]=2)[CH:10]=1)=[O:5])[CH3:2].[Li+].[Cl-].O=P(Cl)(Cl)[Cl:36].CCN(C(C)C)C(C)C>C(#N)C>[Cl:36][C:19]1[C:18]2[C:13](=[CH:14][C:15]([F:31])=[C:16]([O:22][C:23]3[C:28]([CH3:29])=[CH:27][CH:26]=[CH:25][C:24]=3[CH3:30])[CH:17]=2)[N:12]=[C:11]([N:9]2[CH:10]=[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH:7]=[N:8]2)[N:20]=1

Participants

6

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 433294Lithium ChlorideHCID 136379428HCID 136379428, compound

Product 1

HCID 86686095HCID 86686095, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of the above 1-[6-(2,6-dimethyl-phenoxy)-7-fluoro-4-oxo-3,4-dihydro-quinazolin-2-yl]-1H-pyrazole-4-carboxylic acid ethyl ester (5.0 g, 12 mmol), LiCl (2.5 g, 59 mmol), POCl3 (5.5 ml, 59 mmol), DIEA (10 mL, 59 mmol), and acetonitrile (ACN) (50 mL) was heated to reflux for 6 h. The mixture was allowed to cool to rt and then concentrated. The residue was taken up in a minimal amount of DCM and passed through a pad of silica gel, eluting with 50:50 hexanes/EtOAc. The resulting solution was concentrated to provide the titled compound. (5.2 g, >99%). 1H NMR (500 MHz, DMSO-d6): 9.13 (d, J=0.6 Hz, 1H), 8.23 (d, J=0.6 Hz, 1H), 7.92 (d, J=10.7 Hz, 1H), 7.23-7.19 (m, 3H), 7.07 (d, J=8.6 Hz, 1H), 4.36 (q, J=7.1 Hz, 2H), 2.19 (s, 6H), 1.40 (t, J=7.1 Hz, 3H).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 6 h
  3. concentrationconcentrated
  4. washeluting with 50:50 hexanes/EtOAc
  5. concentrationThe resulting solution was concentrated

Sources & evidence

ORD record
ord-85f2d4bef6d24f6daadddd7fab4fdbfe
Source dataset
uspto-grants-2014_08
Patent number
US08796263B2

Reaction notes

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