Trifluoroacetic acid methylene chloride → (S)-4-(4-aminophenylthio)-3-(7-isopropylquinazolin-4-ylamino)-N-(1-phenylethyl)benzamide

HRID 884005ノート

反応式

HRID 884005 の反応式
[CH:1]([C:4]1[CH:13]=[C:12]2[C:7]([C:8]([NH:14][C:15]3[CH:20]=[C:19]([C:21](=[O:31])[NH:22][C@H:23]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH3:24])[CH:18]=[CH:17][C:16]=3[S:32][C:33]3[CH:38]=[CH:37][C:36]([NH:39]C(=O)OC(C)(C)C)=[CH:35][CH:34]=3)=[N:9][CH:10]=[N:11]2)=[CH:6][CH:5]=1)([CH3:3])[CH3:2].C(Cl)Cl.FC(F)(F)C(O)=O>>[NH2:39][C:36]1[CH:35]=[CH:34][C:33]([S:32][C:16]2[CH:17]=[CH:18][C:19]([C:21]([NH:22][C@H:23]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[CH3:24])=[O:31])=[CH:20][C:15]=2[NH:14][C:8]2[C:7]3[C:12](=[CH:13][C:4]([CH:1]([CH3:3])[CH3:2])=[CH:5][CH:6]=3)[N:11]=[CH:10][N:9]=2)=[CH:38][CH:37]=1

参加物

3

反応物 2

HCID 21863450Trifluoroacetic acid methylene chlorideHCID 67040887(S)-tert-butyl 4-(2-(7-isopropylquinazolin-4-ylamino)-4-(1-phenylethylcarbamoyl)phenylthio)phenylcarbamate

生成物 1

HCID 67040746(S)-4-(4-aminophenylthio)-3-(7-isopropylquinazolin-4-ylamino)-N-(1-phenylethyl)benzamide収率 73%

実験手順

The product of Example 91G (36 mg, 0.0568 mmol) was treated with 1:1 v/v methylene chloride/trifluoroacetic acid (3 mL) at room temperature for one hour then concentrated by rotary evaporation. The residue was dissolved in ethyl acetate (50 mL), washed with saturated aqueous sodium hydrogencarbonate (25 mL), water (25 mL), and brine (25 mL) then dried over magnesium sulfate, filtered, and concentrated by rotary evaporation. Purification by silica gel flash chromatography eluting with 3:97 methanol/methylene chloride afforded the title compound as a white solid (22 mg, 0.0412 mmol, 73%). 1H NMR (300 MHz, DMSO-D6) δ ppm 1.31 (d, J=6.99 Hz, 6 H) 1.45 (d, J=7.35 Hz, 3 H) 3.01-3.20 (m, 1 H) 5.07-5.26 (m, 1 H) 5.57 (s, 2 H) 6.61 (d, J=8.46 Hz, 2 H) 6.83 (d, J=8.46 Hz, 1 H) 7.11 (d, J=8.82 Hz, 2 H) 7.17-7.43 (m, 5 H) 7.54-7.64 (m, 2 H) 7.69 (dd, J=8.46, 1.10 Hz, 1 H) 7.89 (d, J=1.47 Hz, 1 H) 8.43 (t, J=4.23 Hz, 2 H) 8.74 (d, J=7.72 Hz, 1 H) 9.88 (s, 1 H); MS (ESI+) m/z 534 (M+H)+, 1067 (2M+H)+; MS (ESI−) m/z 532 (M−H)−.

後処理

  1. concentrationthen concentrated by rotary evaporation
  2. dissolutionThe residue was dissolved in ethyl acetate (50 mL)
  3. washwashed with saturated aqueous sodium hydrogencarbonate (25 mL), water (25 mL), and brine (25 mL)
  4. dry with materialthen dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated by rotary evaporation
  7. customPurification by silica gel flash chromatography
  8. washeluting with 3:97 methanol/methylene chloride

出典と根拠

ORDレコード
ord-ecedbd1536dc463eb291de79a5d8ad46
出典データセット
uspto-grants-2012_08
特許番号
US08236950B2

反応ノート

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