Phenylboronic Acid → HCID 67055950, compound

HRID 2036772Notes

Reaction equation

HRID 2036772 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:13])[NH:5][C:6](=[O:12])[NH:7]2.[C:14]1(B(O)O)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(=O)(O)[O-].[Na+]>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:14]1([C:2]2[CH:11]=[CH:10][CH:9]=[C:8]3[C:3]=2[C:4](=[O:13])[NH:5][C:6](=[O:12])[NH:7]3)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

7

Reactant 3

HCID 66827Phenylboronic AcidHCID 516892Sodium BicarbonateHCID 196042325-Bromoquinazoline-2,4(1H,3H)-dione

Product 1

HCID 67055950HCID 67055950, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

See J. Med. Chem., 50(7):1675 (2007), 76759-011. To a mixture of 5-bromoquinazoline-2,4(1H,3H)-dione (900 mg, 3.73 mmol) and Pd(Ph3P)4 (216 mg, 0.187 mmol) in DME (90 mL) was added phenylboronic acid (683 mg, 5.60 mmol) followed by a solution of sodium bicarbonate (941 mg, 11.2 mmol) in water (30 mL) and the reaction heated at reflux for 40 h. At the conclusion of this period, the organic solvent was removed under reduced pressure. The resulting mixture was filtered and the solid washed with water. The solid was concentrated under reduced pressure from MeOH/DCM to remove the water to yield 5-phenylquinazoline-2,4(1H,3H)-dione as an off-white solid. The 5-phenylquinazoline-2,4(1H,3H)-dione (9.64 g, 40.4 mmol) was added to POCl3 (75 mL, 810 mmol) followed by PhN(CH3)2 (10.3 mL, 81.0 mmol). Upon completion of addition, the reaction mixture was heated to reflux (105° C.) where it was stirred for 2 hours. After this time, the reaction mixture was allowed to cool to ambient temperature. Once at the prescribed temperature, the reaction mixture was concentrated under reduced pressure, diluted with DCM and then quenched by the addition of cold 1M K3PO4 solution. The organic layer was separated and the aqueous layer was extracted twice with DCM. The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure to yield a residue. The residue was purified by ISCO chromatography (330 g column) using hexanes/EtOAc (0-25% over 20 min, flow rate 100 mL/min) to give 2,4-dichloro-5-phenylquinazoline (7.11 g, 63.9% yield) as a yellow solid. 1H NMR (400 MHz, chloroform-d) ppm 8.04 (1H, m) 7.96 (1H, m) 7.59 (1H, dd, J=7.28, 1.25 Hz) 7.45 (3H, dd, J=5.02, 1.76 Hz) 7.32 (2H, m).

Workup

  1. temperaturethe reaction heated
  2. temperatureat reflux for 40 h
  3. customAt the conclusion of this period, the organic solvent was removed under reduced pressure
  4. filtrationThe resulting mixture was filtered
  5. washthe solid washed with water
  6. concentrationThe solid was concentrated under reduced pressure from MeOH/DCM
  7. customto remove the water

Sources & evidence

ORD record
ord-4cd2f2825587499392291d94a5c03485
Source dataset
uspto-grants-2013_11
Patent number
US08575184B2

Reaction notes

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