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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 605387
Notes
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Reaction equation

HRID 605387 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 431F (0.572 g, 2.768 mmol) and methyl 3-amino-4-(4-(tert-butoxycarbonylamino)phenylthio)benzoate the product of Example 385C or Example 432C (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-4fac3d19bc19441e936f13e63dda69dd
Source dataset
uspto-grants-2011_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07910595B2

Reaction notes

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