6-Bromo4-(3-chloro-4-fluoroanilino)quinazoline hydrochloride salt → HCID 9956298, compound

HRID 2184673Notes

Reaction equation

HRID 2184673 reaction equation
Cl.Br[C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[N:9]=[CH:8][N:7]=[C:6]2[NH:13][C:14]1[CH:19]=[CH:18][C:17]([F:20])=[C:16]([Cl:21])[CH:15]=1.[O:22]1[CH2:27][CH2:26][N:25]([CH2:28][CH2:29][C:30]2[S:34][C:33](B(OC(C)C)OC(C)C)=[CH:32][CH:31]=2)[CH2:24][CH2:23]1>>[Cl:21][C:16]1[CH:15]=[C:14]([CH:19]=[CH:18][C:17]=1[F:20])[NH:13][C:6]1[C:5]2[C:10](=[CH:11][CH:12]=[C:3]([C:33]3[S:34][C:30]([CH2:29][CH2:28][N:25]4[CH2:26][CH2:27][O:22][CH2:23][CH2:24]4)=[CH:31][CH:32]=3)[CH:4]=2)[N:9]=[CH:8][N:7]=1

Participants

3

Reactant 2

HCID 224783756-Bromo4-(3-chloro-4-fluoroanilino)quinazoline hydrochloride saltHCID 22478393HCID 22478393, compound

Product 1

HCID 9956298HCID 9956298, compoundYield 27%

Procedure

Using an analogous procedure to that described in Example 5 except that the reaction mixture was heated to reflux for 4 hours, 6-bromo-4-(3-chloro-4-fluoroanilino)quinazoline hydrochloride salt was reacted with di-isopropyl 5-(2-morpholinoethyl)thien-2-ylboronate. The reaction mixture was cooled to ambient temperature and partitioned between methylene chloride and water. The organic phase was washed with brine, dried (MgSO4) and evaporated. The residue was triturated under a mixture of hexane and ethyl acetate to give 4-(3-chloro-4-fluoroanilino)-6-[5-(2-morpholinoethyl)thien-2-yl]quinazoline in 27% yield; NMR Spectrum: 2.6-2.7 (t, 2H), 3.0 (t, 2H), 3.65 (t, 4H), 7.0 (d, 1H), 7.45 (t, 1H), 7.55 (d, 1H), 7.8 (m, 2H), 8.1 (m, 1H), 8.2 (m, 1H), 8.6 (s, 1H), 8.75 (d, 1H), 9.95 (broad s, 1H); Elemental Analysis: Found C, 59.0; H, 4.9; N, 11.3; C24H22ClFN4OS 1H2O requires C, 59.2; H, 5.0; N, 11.5%.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 4 hours
  3. custompartitioned between methylene chloride and water
  4. washThe organic phase was washed with brine
  5. dry with materialdried (MgSO4)
  6. customevaporated
  7. customThe residue was triturated under a mixture of hexane and ethyl acetate

Sources & evidence

ORD record
ord-5ea056f98025427cbebed5d8c07139a0
Source dataset
uspto-grants-2002_06
Patent number
US06399602B1

Reaction notes

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