Butane → 4-[4-(1-Benzenesulfonyl-1H-indol-5-ylamino)-quinazolin-6-yl]-benzaldehyde

HRID 983883Notes

Reaction equation

HRID 983883 reaction equation
CCCC.[C:5]1([S:11]([N:14]2[C:22]3[C:17](=[CH:18][C:19]([NH:23][C:24]4[C:33]5[C:28](=[CH:29][CH:30]=[C:31](I)[CH:32]=5)[N:27]=[CH:26][N:25]=4)=[CH:20][CH:21]=3)[CH:16]=[CH:15]2)(=[O:13])=[O:12])[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[CH:35]([C:37]1[CH:42]=[CH:41][C:40](B(O)O)=[CH:39][CH:38]=1)=[O:36].C([O-])([O-])=O.[Na+].[Na+]>C1C=CC(C#N)=CC=1.C1C=CC(C#N)=CC=1.Cl[Pd]Cl.C1(C)C=CC=CC=1>[C:5]1([S:11]([N:14]2[C:22]3[C:17](=[CH:18][C:19]([NH:23][C:24]4[C:33]5[C:28](=[CH:29][CH:30]=[C:31]([C:40]6[CH:41]=[CH:42][C:37]([CH:35]=[O:36])=[CH:38][CH:39]=6)[CH:32]=5)[N:27]=[CH:26][N:25]=4)=[CH:20][CH:21]=3)[CH:16]=[CH:15]2)(=[O:13])=[O:12])[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

Participants

7

Reactant 4

HCID 7843ButaneHCID 10340Sodium CarbonateHCID 5910734-Formylphenylboronic AcidHCID 15450144(1-Benzenesulfonyl-1H-indol-5-yl)-(6-iodo-quinazolin-4-yl)-amine

Product 1

HCID 116706224-[4-(1-Benzenesulfonyl-1H-indol-5-ylamino)-quinazolin-6-yl]-benzaldehydeYield 93.1%

Reagents, catalysts & solvents 2

HCID 498840Bis(benzonitrile)palladium chlorideCatalystHCID 1140TolueneSolvent

Procedure

To a solution of toluene (100 mL) in a 500 mL round-bottom flask equipped with a reflux condenser was added 1,4-bis(diphenyl)phosphino)-butane (4.25 mg, 0.997 mmol) and bis(benzonitrile)dichloro-palladium (385 g, 0.997 mmol). Nitrogen was bubbled through the reaction mixture for 1 minute and the resulting suspension was stirred at room temperature for 30 minutes. THF (125 mL) and EtOH (50 mL) were then added. To the resulting mixture was added (1-benzenesulfonyl-1H-indol-5-yl)-(6-iodo-quinazolin-4-yl)-amine 20 (3.5 g, 6.6 mmol), 4-formylphenylboronic acid (1.99 g, 13.3 mmol) and 2M aq Na2CO3 (6.7 mL). The mixture was heated at reflux under an atmosphere of N2 for 15 hours. The solvent was removed under reduced pressure and the residue was purified using flash chromatography (silica gel, EtOAc/hexanes 1:1) to provide 3.1 g of 4-[4-(1-benzenesulfonyl-1H-indol-5-ylamino)-quinazolin-6-yl]-benzaldehyde 22 in 92% yield. 1H NMR (DMSO-d6; 400 MHz): δ: 9.24 (s, 1H, NH), 8.84 (s, 1H), 8.33 (dd, 1H, J=8.9 Hz and1.7 Hz), 8.01 (m, 4H), 7.90 (m, 2H), 7.70 (m, 2H), 7.60 (m, 3H), 6.92 (dd, 1H, J=3.7 Hz and 0.6 Hz); MS (Cl) m/e 505.1 (M++1, 100).

Workup

  1. customNitrogen was bubbled through the reaction mixture for 1 minute
  2. additionTHF (125 mL) and EtOH (50 mL) were then added
  3. temperatureThe mixture was heated
  4. temperatureat reflux under an atmosphere of N2 for 15 hours
  5. customThe solvent was removed under reduced pressure
  6. customthe residue was purified

Sources & evidence

ORD record
ord-643d58918bbd4fd7a21358d83970db99
Source dataset
uspto-grants-2005_03
Patent number
US06867201B2

Reaction notes

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