Ethyl Acetate → N-(5-formyl-2-methylphenyl)-4-[(4-phenylquinazolin-2-yl)amino]benzamide

HRID 406820Notes

Reaction equation

HRID 406820 reaction equation
CN(OC)[C:3](=[O:37])[C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([NH:11][C:12]([C:14]2[CH:19]=[CH:18][C:17]([NH:20][C:21]3[N:30]=[C:29]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[N:22]=3)=[CH:16][CH:15]=2)=[O:13])[CH:5]=1.[H-].C([Al+]CC(C)C)C(C)C.C(OCC)(=O)C>ClCCl>[CH:3]([C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([NH:11][C:12](=[O:13])[C:14]2[CH:15]=[CH:16][C:17]([NH:20][C:21]3[N:30]=[C:29]([C:31]4[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=4)[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[N:22]=3)=[CH:18][CH:19]=2)[CH:5]=1)=[O:37]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 21225700DiisobutylaluminumhydrideHCID 25070163N,4-dimethyl-N-(methyloxy)-3-[({4-[(4-phenylquinazolin-2-yl)amino]phenyl}carbonyl)amino]benzamide

Product 1

HCID 57662899N-(5-formyl-2-methylphenyl)-4-[(4-phenylquinazolin-2-yl)amino]benzamideYield 77%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A stirred solution of N,4-dimethyl-N-(methyloxy)-3-[({4-[(4-phenylquinazolin-2-yl)amino]phenyl}carbonyl)amino]benzamide (1.16 g, 2.24 mmol) in dichloromethane (150 mL) was cooled to −78° C. under nitrogen and a 1 M solution of diisobutylaluminum hydride in dichloromethane (6.7 mL, 6.7 mmol) was added dropwise over 30 min. The cooled solution was stirred for additional 1 h, then excess ethyl acetate was added to quench the reaction. The cooling bath was removed and the mixture was warmed to 0° C. using an ice bath. Methanol (2 mL) and then water (2 mL) was added carefully to the reaction mixture with vigorous stifling. A solution of 1 N hydrochloric acid (20 mL) was then added and the precipitates that formed were collected. The filtrates were separated and the aqueous layer was extracted with dichloromethane. The combined organic extracts were dried over sodium sulfate and concentrated on a rotary evaporator to give yellow solid that was combined with the previously collected precipitate, washed with water and dried under reduced pressure to give N-(5-formyl-2-methylphenyl)-4-[(4-phenylquinazolin-2-yl)amino]benzamide (791 mg, 77%). 1H NMR (400 MHz, CD3OD): δ 9.98 (s, 1H), 8.23 (d, 1H), 8.06 (d, 2H), 7.98 (d, 2H), 7.95 (d, 1H), 7.85 (m, 3H), 7.78 (q, 3H), 7.03 (m, 1H), 7.76 (t, 3H), 7.46 (d, 1H), 2.43 (s, 3H). MS (EI) for C29H22N4O2: 459.0 (MH+).

Workup

  1. customto quench
  2. customthe reaction
  3. customThe cooling bath was removed
  4. additionMethanol (2 mL) and then water (2 mL) was added carefully to the reaction mixture with vigorous stifling
  5. additionA solution of 1 N hydrochloric acid (20 mL) was then added
  6. customthe precipitates
  7. customthat formed
  8. customwere collected
  9. customThe filtrates were separated
  10. extractionthe aqueous layer was extracted with dichloromethane
  11. dry with materialThe combined organic extracts were dried over sodium sulfate
  12. concentrationconcentrated on a rotary evaporator
  13. customto give yellow solid
  14. washwashed with water
  15. customdried under reduced pressure

Sources & evidence

ORD record
ord-0f4ef8ebaa8d4b2785020b4015018b67
Source dataset
uspto-grants-2014_06
Patent number
US08754092B2

Reaction notes

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