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Methyl 3-amino-4-((4-((tert-butoxycarbonyl)amino)phenyl)thio)benzoate → Methyl 4-(4-(tert-butoxycarbonylamino)phenylthio)-3-(7-isopropylquinazolin-4-ylamino)benzoate

HRID 884007
Notes
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Reaction equation

HRID 884007 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH:12]([CH3:14])[CH3:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[NH2:15][C:16]1[CH:17]=[C:18]([CH:23]=[CH:24][C:25]=1[S:26][C:27]1[CH:32]=[CH:31][C:30]([NH:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])=[CH:29][CH:28]=1)[C:19]([O:21][CH3:22])=[O:20]>C(O)C>[C:37]([O:36][C:34]([NH:33][C:30]1[CH:29]=[CH:28][C:27]([S:26][C:25]2[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][C:16]=2[NH:15][C:2]2[C:11]3[C:6](=[CH:7][C:8]([CH:12]([CH3:14])[CH3:13])=[CH:9][CH:10]=3)[N:5]=[CH:4][N:3]=2)=[CH:32][CH:31]=1)=[O:35])([CH3:40])([CH3:38])[CH3:39]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 2

HCID 59376792Methyl 3-amino-4-((4-((tert-butoxycarbonyl)amino)phenyl)thio)benzoate2×HCID 866155654-Chloro-7-isopropylquinazoline

Product 1

HCID 67040925Methyl 4-(4-(tert-butoxycarbonylamino)phenylthio)-3-(7-isopropylquinazolin-4-ylamino)benzoateYield 33%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

The products of Example 91F (0.572 g, 2.768 mmol) and methyl 3-amino-4-(4-(tert-butoxycarbonylamino)phenylthio)benzoate the product of Example 89C or Example 92C (0.902 g, 2.409 mmol) were reacted in anhydrous ethanol (25 mL) under a nitrogen atmosphere at reflux for 30 minutes. The reaction was cooled and concentrated by rotary evaporation. The residue was dissolved in methylene chloride (50 mL) and washed with saturated aqueous sodium hydrogencarbonate (25 mL) and water (25 mL). The organic phase was 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 (0.505 g, 0.927 mmol, 33%). 1H NMR (300 MHz, DMSO-D6) δ ppm 1.32 (d, J=6.99 Hz, 6 H) 1.48 (s, 9 H) 2.99-3.21 (m, 1 H) 3.83 (s, 3 H) 6.93 (d, J=8.46 Hz, 1 H) 7.37 (d, J=8.82 Hz, 2 H) 7.55 (d, J=8.82 Hz, 2 H) 7.55-7.64 (m, 2 H) 7.75 (dd, J=8.46, 1.84 Hz, 1 H) 7.91 (d, J=1.84 Hz, 1 H) 8.41 (d, J=8.46 Hz, 1 H) 8.45 (s, 1 H) 9.62 (s, 1 H) 9.92 (s, 1 H). MS (ESI+) m/z 545 (M+H)+.

Workup

  1. temperatureat reflux for 30 minutes
  2. temperatureThe reaction was cooled
  3. concentrationconcentrated by rotary evaporation
  4. dissolutionThe residue was dissolved in methylene chloride (50 mL)
  5. washwashed with saturated aqueous sodium hydrogencarbonate (25 mL) and water (25 mL)
  6. dry with materialThe organic phase was dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated by rotary evaporation
  9. customPurification by silica gel flash chromatography
  10. washeluting with 3:97 methanol/methylene chloride

Sources & evidence

ORD record
ord-29212ca0551049a5b289070c08bb4623
Source dataset
uspto-grants-2012_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08236950B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes