Hydrochloric Acid → 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-[(2S)-pyrrolidin-2-ylmethoxy]quinazoline hydrochloride

HRID 1948935Notes

Reaction equation

HRID 1948935 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:26][CH3:27])=[C:9]([O:12][CH2:13][C@@H:14]3[CH2:18][CH2:17][CH2:16][N:15]3C(OC(C)(C)C)=O)[CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:28][C:29]1[C:30]([F:36])=[C:31]([CH:33]=[CH:34][CH:35]=1)[NH2:32].Cl>C(#N)C>[ClH:1].[Cl:28][C:29]1[C:30]([F:36])=[C:31]([CH:33]=[CH:34][CH:35]=1)[NH:32][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:26][CH3:27])=[C:9]([O:12][CH2:13][C@@H:14]3[CH2:18][CH2:17][CH2:16][NH:15]3)[CH:10]=2)[N:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 750143-Chloro-2-fluoroanilineHCID 866008264-chloro-7-methoxy-6-{[(2S)-1-tert-butoxycarbonylpyrrolidin-2-yl]methoxy}quinazoline

Product 1

HCID 685223024-(3-chloro-2-fluoroanilino)-7-methoxy-6-[(2S)-pyrrolidin-2-ylmethoxy]quinazoline hydrochlorideYield 100%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 4-chloro-7-methoxy-6-{[(2S)-1-tert-butoxycarbonylpyrrolidin-2-yl]methoxy}quinazoline in acetonitrile (120 ml), 3-chloro-2-fluoroaniline (1.4 ml, 12.7 mmole) and hydrogen chloride (4.0M in 1,4-dioxane) (13 ml, 52 mmole) were added. This mixture was heated to reflux for one hour. After cooling to ambient temperature the precipitate was filtered off, washed with acetonitrile followed by diethylether and dried under vacuum to give 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-{[(2S)-pyrrolidin-2-yl]methoxy}quinazoline hydrochloride as a yellow solid (5.73 g, 100%); 1H NMR Spectrum: (DMSO d6) 1.70-2.10 (m, 3H); 2.10-2.30 (m, 1H); 3.00-3.80 (m, 2H); 3.97-4.10 (m, 4H); 4.45-4.57 (m, 2H); 7.32-7.38 (m, 1H); 7.46 (s, 1H); 7.49-7.55 (m, 1H); 7.59-7.65 (m, 1H); 8.65 (s, 1H); 8.81 (s, 1H); 9.31 (bs, 1H); 9.67 (bs, 1H); 12.09 (bs, 1H); Mass Spectrum: (M+H)+ 403.

Workup

  1. temperatureThis mixture was heated
  2. temperatureto reflux for one hour
  3. filtrationwas filtered off
  4. washwashed with acetonitrile
  5. customdried under vacuum

Sources & evidence

ORD record
ord-af2fafc4327b4942a164291d032d04c6
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

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