Hydrochloric Acid → Vandetanib hydrochloride

HRID 238090Notes

Reaction equation

HRID 238090 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH:16]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Br:23][C:24]1[CH:30]=[CH:29][C:27]([NH2:28])=[C:26]([F:31])[CH:25]=1.Cl>C(O)(C)C>[ClH:1].[Br:23][C:24]1[CH:30]=[CH:29][C:27]([NH:28][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:14][CH2:15][CH:16]4[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]4)=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][N:3]=2)=[C:26]([F:31])[CH:25]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 1230504-Bromo-2-fluoroanilineHCID 117822304-Chloro-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazoline

Product 1

HCID 23133323Vandetanib hydrochlorideYield 95.8%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent2×

Procedure

A suspension of 4-chloro-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (200 mg, 0.62 mmol) and 4-bromo-2-fluoroaniline (142 mg, 0.74 mmol) in isopropanol (3 ml) containing 6N hydrogen chloride in isopropanol (110 μl, 0.68 ml) was heated at reflux for 1.5 hours. After cooling, the precipitate was collected by filtration, washed with isopropanol followed by ether and dried under vacuum to give 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline hydrochloride (304 mg, 90%).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1.5 hours
  3. temperatureAfter cooling
  4. filtrationthe precipitate was collected by filtration
  5. washwashed with isopropanol
  6. customdried under vacuum

Sources & evidence

ORD record
ord-066711626caf41f08c53419fad28759d
Source dataset
uspto-grants-2014_02
Patent number
US08642608B2

Reaction notes

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