Potassium Carbonate → 4-[(3-Chloro-2-fluoro-phenyl)amino]-6-(1,4-dioxa-spiro[4.5]decan-8-yl-oxy)-7-methoxy-quinazoline

HRID 1672122Notes

Reaction equation

C(=O)([O-])[O-].[K+].[K+].CS([O:11][CH:12]1[CH2:21][CH2:20][C:15]2([O:19][CH2:18][CH2:17][O:16]2)[CH2:14][CH2:13]1)(=O)=O.[Cl:22][C:23]1[C:24]([F:43])=[C:25]([NH:29][C:30]2[C:39]3[C:34](=[CH:35][C:36]([O:41][CH3:42])=[C:37](O)[CH:38]=3)[N:33]=[CH:32][N:31]=2)[CH:26]=[CH:27][CH:28]=1>CN(C)C=O.O.C(OCC)(=O)C>[Cl:22][C:23]1[C:24]([F:43])=[C:25]([NH:29][C:30]2[C:39]3[C:34](=[CH:35][C:36]([O:41][CH3:42])=[C:37]([O:11][CH:12]4[CH2:21][CH2:20][C:15]5([O:19][CH2:18][CH2:17][O:16]5)[CH2:14][CH2:13]4)[CH:38]=3)[N:33]=[CH:32][N:31]=2)[CH:26]=[CH:27][CH:28]=1

Participants

Conditions

Temperature: 80 °C

Procedure

At 50° C. 12.5 g potassium carbonate and 16 g 8-methanesulphonyloxy-1,4-dioxa-spiro[4,5]decane (cf for example Journal of Medicinal Chemistry (1992), 35(12), 2243-7) are added to 18.1 g 4-[(3-chloro-2-fluoro-phenyl)amino]-6-hydroxy-7-methoxy-quinazoline (cf for example Bioorganic & Medicinal Chemistry Letters (2006), 16(18), 4908-4912) in 125 ml dimethylformamide and the mixture is stirred for 18 hours at 80° C. Another 4.7 g potassium carbonate and 4.0 g of 8-methanesulphonyloxy-1,4-dioxa-spiro[4,5]decane are added and the mixture is stirred for another 7 hours at 80° C. The reaction mixture is cooled, diluted with water and ethyl acetate and the precipitate formed is suction filtered and dried.

Workup

customAt 50° C
stirringthe mixture is stirred for another 7 hours at 80° C
temperatureThe reaction mixture is cooled
customthe precipitate formed
filtrationfiltered
customdried

Sources & evidence

ORD record: ord-c921a31264244f518bb09e6c456b699d
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07998949B2

Reaction notes

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