HCID 22648049, compound → HCID 22647964, compound

HRID 394085Notes

Reaction equation

HRID 394085 reaction equation
[CH3:1][Mg]Br.[Cl:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([Cl:11])[C:6]=1[N:12]1[C:21]2[C:16](=[C:17]([C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=3[Cl:31])[CH:18]=[C:19]([O:22][CH3:23])[CH:20]=2)[CH:15]=[N:14][C:13]1=[O:32]>C1COCC1>[Cl:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([Cl:11])[C:6]=1[N:12]1[C:21]2[C:16](=[C:17]([C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=3[Cl:31])[CH:18]=[C:19]([O:22][CH3:23])[CH:20]=2)[CH2:15][N:14]([CH3:1])[C:13]1=[O:32]

Participants

4

Reactant 2

HCID 22648049HCID 22648049, compound2×HCID 178418573HCID 178418573, compound

Product 1

HCID 22647964HCID 22647964, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of methylmagnesium bromide (3.0M ethyl ether, 0.5 mL) was added dropwise to 1-(2,6-dichlorophenyl)-5-(2-chloro-4-fluorophenyl)-7-(methoxy)-2(1H)-quinazolinone (230 mg, 0.511 mmol) (INTERMEDIATE 56) in THF (10 mL) at −78C. After 20 min the solution was warmed to 0° C. After 40 min at 0° C. the solution was partitioned between NaHCO3 and EtOAc. The phases were separated and the organic phase washed with brine, dried over MgSO4, filtered and concentrated. The crude was absorbed on SiO2 and purified by silica gel chromatography using 2% acetone in DCM as the eluent to give 1-(2,6-dichlorophenyl)-3-methyl-5-(2-chloro-4-fluorophenyl)-7-methoxy-3,4-dihydro-2(1H)-quinazolinone. 1H NMR(CDCl3, 500 MHz): diastereomeric atropisomers δ 1.29 (m, 3H), 3.69 (s, 3H), 4.31 (m, 0.5H), 4.41 (m, 0.5H), 5.32 (m, 0.5H), 5.35 (m, 0.5H), 5.76 (m, 1H), 6.37 (d, 0.5H, J=2.5 Hz), 6.44 (d, 0.5H, J=2.2 Hz), 7.08-7.14 (m, 1H), 7.28-7.40 (m, 3H), 7.50-7.56 (m, 2H). MS(ES) 465 (M+H); LC 1: 3.63 min. and MS(ES) 465 (M+H); LC 1: 3.71 min.

Workup

  1. customAfter 40 min at 0° C. the solution was partitioned between NaHCO3 and EtOAc
  2. customThe phases were separated
  3. washthe organic phase washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude was absorbed on SiO2
  8. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-b359d106feb842adb9aa9b2e587bf7cd
Source dataset
uspto-grants-2004_10
Patent number
US06809199B2

Reaction notes

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