(S)-tert-butyl 4-(2-amino-4-(1-phenylethylcarbamoyl)phenylthio)-phenylcarbamate → (S)-tert-butyl 4-(2-(7-isopropylquinazolin-4-ylamino)-4-(1-phenylethylcarbamoyl)phenylthio)phenylcarbamate

HRID 605384Notes

Reaction equation

HRID 605384 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([C:8](=[O:18])[NH:9][C@H:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH3:11])[CH:5]=[CH:4][C:3]=1[S:19][C:20]1[CH:25]=[CH:24][C:23]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:22][CH:21]=1.Cl[C:35]1[C:44]2[C:39](=[CH:40][C:41]([CH:45]([CH3:47])[CH3:46])=[CH:42][CH:43]=2)[N:38]=[CH:37][N:36]=1>C(O)C>[CH:45]([C:41]1[CH:40]=[C:39]2[C:44]([C:35]([NH:1][C:2]3[CH:7]=[C:6]([C:8](=[O:18])[NH:9][C@H:10]([C:12]4[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=4)[CH3:11])[CH:5]=[CH:4][C:3]=3[S:19][C:20]3[CH:21]=[CH:22][C:23]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:24][CH:25]=3)=[N:36][CH:37]=[N:38]2)=[CH:43][CH:42]=1)([CH3:47])[CH3:46]

Participants

4

Reactant 2

HCID 67041066(S)-tert-butyl 4-(2-amino-4-(1-phenylethylcarbamoyl)phenylthio)-phenylcarbamateHCID 866155654-Chloro-7-isopropylquinazoline

Product 1

HCID 67040887(S)-tert-butyl 4-(2-(7-isopropylquinazolin-4-ylamino)-4-(1-phenylethylcarbamoyl)phenylthio)phenylcarbamateYield 74.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

(S)-tert-butyl 4-(2-amino-4-(1-phenylethylcarbamoyl)phenylthio)-phenylcarbamate (50 mg, 0.1078 mmol) and the product of Example 431F (24.5 mg, 0.1186 mmol) were heated at reflux in anhydrous ethanol (2 mL) under a nitrogen atmosphere for one hour. The reaction was cooled and concentrated by rotary evaporation. The residue was purified by silica gel flash chromatography eluting with 3:97 methanol/methylene chloride to afford the title compound as an off-white solid (51 mg, 0.0805 mmol, 68%). 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) 1.47 (s, 9 H) 3.03-3.21 (m, 1 H) 5.01-5.29 (m, 1 H) 6.96 (d, J=8.46 Hz, 1 H) 7.16-7.25 (m, 1 H) 7.26-7.43 (m, 3 H) 7.32 (d, J=8.09 Hz, 2 H) 7.51 (d, J=8.82 Hz, 2 H) 7.55-7.63 (m, 2 H) 7.72 (dd, J=8.46, 1.47 Hz, 1 H) 7.94 (d, J=1.47 Hz, 1 H) 8.41 (d, J=8.82 Hz, 1 H) 8.44 (s, 1 H) 8.80 (d, J=8.09 Hz, 1 H) 9.58 (s, 1 H) 9.95 (s, 1 H); MS (ESI+) m/z 634 (M+H)+; MS (ESI−) m/z 632 (M−H)−.

Workup

  1. temperatureThe reaction was cooled
  2. concentrationconcentrated by rotary evaporation
  3. customThe residue was purified by silica gel flash chromatography
  4. washeluting with 3:97 methanol/methylene chloride

Sources & evidence

ORD record
ord-934c688954144000a21bd03b3181e107
Source dataset
uspto-grants-2011_03
Patent number
US07910595B2

Reaction notes

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