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

HRID 1948935노트

반응식

HRID 1948935 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-af2fafc4327b4942a164291d032d04c6
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08399667B2

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