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

HRID 884005노트

반응식

HRID 884005 반응식
[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

참가 물질

3

반응물 2

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

생성물 1

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

실험 절차

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)−.

후처리

  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

출처 및 근거

ORD 기록
ord-ecedbd1536dc463eb291de79a5d8ad46
출처 데이터셋
uspto-grants-2012_08
특허 번호
US08236950B2

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