Dimethylformamide → 3-(2-Chloro-4-morpholin-4-ylquinazolin-8-yl)-phenol

HRID 2092553Notes

Reaction equation

HRID 2092553 reaction equation
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([Cl:12])[N:8]=[C:7]2[N:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.[OH:19][C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][CH:25]=1.C(=O)([O-])[O-].[Na+].[Na+].CN(C=O)C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[Cl:12][C:9]1[N:8]=[C:7]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)[C:6]2[C:11](=[C:2]([C:24]3[CH:25]=[C:20]([OH:19])[CH:21]=[CH:22][CH:23]=3)[CH:3]=[CH:4][CH:5]=2)[N:10]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 2734359(3-hydroxyphenyl)boronic AcidHCID 866657654-(8-Bromo-2-chloroquinazolin-4-yl)morpholine

Product 1

HCID 866657663-(2-Chloro-4-morpholin-4-ylquinazolin-8-yl)-phenolYield 60.7%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
95 °C

Procedure

To a 50 mL round bottom flask, 8-bromo-2-chloro-4-morpholin-4-yl-quinazoline (150 mg, 0.00046 mol), 3-hydroxyphenylboronic acid (57 mg, 0.00041 mol), sodium carbonate (97 mg, 0.00091 mol), DMF (10 mL) and water (5 mL) were added. The reaction mixture was degassed with nitrogen for 5-10 min. To the same flask Pd(PPh3)2Cl2 (16 mg, 0.000022 mol) was added and again degassed with nitrogen for 5-10 min. The reaction mixture was stirred at 95° C. for 2 h. The reaction mixture was cooled and diluted with ethyl acetate. The organic layer was washed with water, brine and dried over sodium sulfate. The solvent was removed under reduced pressure to afford the crude residue. The crude product was purified using column chromatography (60-120 silica gel, 1% MeOH in chloroform) to yield the desired title product (85 mg, 46%). 1H NMR: (300 MHz, CDCl3): δ 7.70-7.78 (m, 2H), 7.40-7.44 (m, 1H), 7.20-7.26 (m, 1H), 7.03-7.05 (m, 2H), 6.78-6.83 (m, 1H), 3.81-3.83 (m, 8H); LC-MS (ESI): Calculated mass: 341.1; Observed mass: 342.1 [M+H]+ (RT: 1.53 min).

Workup

  1. customThe reaction mixture was degassed with nitrogen for 5-10 min
  2. customagain degassed with nitrogen for 5-10 min
  3. temperatureThe reaction mixture was cooled
  4. additiondiluted with ethyl acetate
  5. washThe organic layer was washed with water, brine
  6. dry with materialdried over sodium sulfate
  7. customThe solvent was removed under reduced pressure
  8. customto afford the crude residue
  9. customThe crude product was purified

Sources & evidence

ORD record
ord-12e1c43297fb452e97773ef151faa955
Source dataset
uspto-grants-2013_05
Patent number
US08440662B2

Reaction notes

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