Butyronitrile → Saracatinib

HRID 1873653Notes

Reaction equation

HRID 1873653 reaction equation
P(Cl)(Cl)(Cl)=O.[CH3:6][N:7]1[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][O:15][C:16]2[CH:25]=[C:24]3[C:19]([C:20](=O)[NH:21][CH:22]=[N:23]3)=[C:18]([O:27][CH:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)[CH:17]=2)[CH2:9][CH2:8]1.C(N(C(C)C)CC)(C)C.C(#N)CCC.[Cl:48][C:49]1[C:54]([NH2:55])=[C:53]2[O:56][CH2:57][O:58][C:52]2=[CH:51][CH:50]=1>O>[Cl:48][C:49]1[C:54]([NH:55][C:20]2[C:19]3[C:24](=[CH:25][C:16]([O:15][CH2:14][CH2:13][N:10]4[CH2:9][CH2:8][N:7]([CH3:6])[CH2:12][CH2:11]4)=[CH:17][C:18]=3[O:27][CH:28]3[CH2:29][CH2:30][O:31][CH2:32][CH2:33]3)[N:23]=[CH:22][N:21]=2)=[C:53]2[O:56][CH2:57][O:58][C:52]2=[CH:51][CH:50]=1

Participants

7

Reactant 5

HCID 8008ButyronitrileHCID 24813Phosphorus oxychloride2×HCID 81531DiisopropylethylamineHCID 113672535-Chloro-1,3-benzodioxol-4-amineHCID 1355255577-(2-(4-Methylpiperazin-1-yl)ethoxy)-5-((tetrahydro-2H-pyran-4-yl)oxy)quinazolin-4(3H)-one

Product 1

HCID 10302451Saracatinib

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
96 °C

Procedure

Under an atmosphere of nitrogen gas, phosphoryl chloride (0.07 ml) was added to a stirred mixture of 7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-tetrahydropyran-4-yloxy-3,4-dihydroquinazolin-4-one (0.2 g), diisopropylethylamine (0.22 ml) and butyronitrile (2 ml) that had been heated to 96° C. and the resultant mixture was heated to 96° C. for 4 hours. A second portion (0.12 ml) of phosphoryl chloride was added and the resultant mixture was heated to 96° C. for 1.7 hours. 6-Chloro-2,3-methylenedioxyaniline (0.098 g) was added and the resultant mixture was heated to 96° C. for 2 hours. The mixture was allowed to cool to ambient temperature. Water (2 ml) was added and the organic layer was separated. The aqueous layer was washed with butyronitrile (1 ml). The aqueous layer was basified to pH9 by the addition of concentrated aqueous sodium hydroxide solution (47% w/w) and extracted with n-butanol (2×2 ml). The resultant organic layers were combined and evaporated. There was thus obtained 4-(6-chloro-2,3-methylenedioxyanilino)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-tetrahydropyran-4-yloxyquinazoline (0.094 g).

Workup

  1. temperatureto cool to ambient temperature
  2. customthe organic layer was separated
  3. washThe aqueous layer was washed with butyronitrile (1 ml)
  4. additionThe aqueous layer was basified to pH9 by the addition of concentrated aqueous sodium hydroxide solution (47% w/w)
  5. extractionextracted with n-butanol (2×2 ml)
  6. customevaporated

Sources & evidence

ORD record
ord-ea2530e94e4e4937917cb10b46b789e2
Source dataset
uspto-grants-2012_11
Patent number
US08304417B2

Reaction notes

Loading…