Hydrochloric Acid → Vandetanib hydrochloride

HRID 577361Notes

Reaction equation

HRID 577361 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-8dbac08902b849188148fa0da8592f01
Source dataset
uspto-grants-2015_05
Patent number
US09040548B2

Reaction notes

Loading…