Phosphorus oxychloride → N-(5-Chlorobenzo[d][1,3]dioxol-4-yl)-5,7-difluoroquinazolin-4-amine

HRID 1873648Notes

Reaction equation

HRID 1873648 reaction equation
P(Cl)(Cl)(Cl)=O.[F:6][C:7]1[CH:16]=[C:15]([F:17])[CH:14]=[C:13]2[C:8]=1[C:9](=O)[NH:10][CH:11]=[N:12]2.[Cl:19][C:20]1[C:25]([NH2:26])=[C:24]2[O:27][CH2:28][O:29][C:23]2=[CH:22][CH:21]=1.C(N(C(C)C)CC)(C)C>ClC1C=CC=CC=1>[Cl:19][C:20]1[C:25]([NH:26][C:9]2[C:8]3[C:13](=[CH:14][C:15]([F:17])=[CH:16][C:7]=3[F:6])[N:12]=[CH:11][N:10]=2)=[C:24]2[O:27][CH2:28][O:29][C:23]2=[CH:22][CH:21]=1

Participants

6

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 113672535-Chloro-1,3-benzodioxol-4-amineHCID 1355106875,7-Difluoro-3,4-dihydroquinazolin-4-one

Product 1

HCID 11695717N-(5-Chlorobenzo[d][1,3]dioxol-4-yl)-5,7-difluoroquinazolin-4-amine

Reagents, catalysts & solvents 1

HCID 7964ChlorobenzeneSolvent

Conditions

Temperature
95 °C

Procedure

Phosphoryl chloride (4.96 ml) was added over a period of 40 minutes to a stirred mixture of 5,7-difluoro-3,4-dihydroquinazolin-4-one (6.5 g), chlorobenzene (64.9 ml), 6-chloro-2,3-methylenedioxyaniline (7.08 g) and diisopropylethylamine (7.47 ml) that had been heated to 95° C. under an atmosphere of nitrogen gas. The resultant reaction mixture was heated at 95° C. for 5 hours. The reaction mixture was cooled to 18° C. and stirred for 30 minutes. Stirring was stopped and the reaction mixture was allowed to stand for 30 minutes. The mixture was filtered and the isolated solid was washed with chlorobenzene (2×23 ml) and dried in vacuo at 45° C. There was thus obtained 4-(6-chloro-2,3-methylenedioxyanilino)-5,7-difluoroquinazoline as a mono-hydrochloride salt (8.9 g, 96.5% HPLC purity using Method A, retention time 4.46 minutes); m.p. 234-237° C.; NMR Spectrum: (DMSOd6) 5.5-6.0 (br s, 1H), 6.15 (s, 2H), 7.0 (d, 1H), 7.1 (d, 1H), 7.6 (d, 1H), 7.8 (m, 1H), 8.7 (s, 1H).

Workup

  1. customThe resultant reaction mixture
  2. temperaturewas heated at 95° C. for 5 hours
  3. temperatureThe reaction mixture was cooled to 18° C.
  4. stirringStirring
  5. waitto stand for 30 minutes
  6. filtrationThe mixture was filtered
  7. washthe isolated solid was washed with chlorobenzene (2×23 ml)
  8. customdried in vacuo at 45° C

Sources & evidence

ORD record
ord-f3d01a9167aa4943bd9bc52bd2919d6c
Source dataset
uspto-grants-2012_11
Patent number
US08304417B2

Reaction notes

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