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

HRID 1948935ノート

反応式

HRID 1948935 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-af2fafc4327b4942a164291d032d04c6
出典データセット
uspto-grants-2013_03
特許番号
US08399667B2

反応ノート

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