Hydrochloric Acid → 4-(5-chloronaphth-1-ylamino)-7-methoxy-5-(N-methylpiperidin-4-yloxy)quinazoline dihydrochloride

HRID 1826261Notes

Reaction equation

HRID 1826261 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:20][CH3:21])=[CH:9][C:10]=2[O:12][CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)[N:5]=[CH:4][N:3]=1.[Cl:22][C:23]1[CH:32]=[CH:31][CH:30]=[C:29]2[C:24]=1[CH:25]=[CH:26][CH:27]=[C:28]2[NH2:33].Cl>C(O)(C)C>[ClH:1].[ClH:22].[Cl:22][C:23]1[CH:32]=[CH:31][CH:30]=[C:29]2[C:24]=1[CH:25]=[CH:26][CH:27]=[C:28]2[NH:33][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:20][CH3:21])=[CH:9][C:10]=2[O:12][CH:13]2[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]2)[N:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 44550535-Chloronaphthalen-1-amineHCID 113812714-Chloro-7-methoxy-5-[(1-methylpiperidin-4-yl)oxy]quinazoline

Product 1

HCID 221407714-(5-chloronaphth-1-ylamino)-7-methoxy-5-(N-methylpiperidin-4-yloxy)quinazoline dihydrochlorideYield 159.7%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent2×

Procedure

A mixture of 4-chloro-7-methoxy-5-(N-methylpiperidin-4-yloxy)quinazoline (0.08 g), 5-chloro-1-naphthylamine (0.055 g), 6.2M hydrogen chloride in isopropanol (0.044 ml) and isopropanol (3 ml) was stirred and heated to reflux for 2 hours. The mixture was cooled to ambient temperature and the precipitate was isolated, washed with diethyl ether and dried under vacuum. There was thus obtained the title compound (0.129 g), a portion of which was treated with a saturated methanolic ammonia solution. The mixture was filtered and the filtrate was evaporated to give the free base; NMR Spectrum: (CDCl3) 1.9–2.1 (m, 4H), 2.22 (s, 3H), 2.25–2.4 (m, 2H), 2.6–2.7 (m, 2H), 3.94 (s, 3H), 4.7 (br s, 1H), 6.6 (s, 1H), 6.9 (s, 1H), 7.4 (m, 1H), 7.62 (d, 1H), 7.7 (m, 1H), 8.0 (m, 2H), 8.25 (d, 1H), 8.46 (s, 1H), 9.9 (br s, 1H); Mass Spectrum: M+H+ 449 and 451.

Workup

  1. temperatureheated
  2. temperatureto reflux for 2 hours
  3. customthe precipitate was isolated
  4. washwashed with diethyl ether
  5. customdried under vacuum

Sources & evidence

ORD record
ord-2907a88a301c4fa2b786cec828fa0374
Source dataset
uspto-grants-2006_05
Patent number
US07049438B2

Reaction notes

Loading…