Potassium Carbonate → 7-(Benzylthio)-4-(2-chloro-3'-fluoro-5-methoxy-[1,1'-biphenyl]-4-yl)quinazoline

HRID 1473683Notes

Reaction equation

HRID 1473683 reaction equation
[CH2:1]([S:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13](Cl)=[N:14][CH:15]=[N:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:20][C:21]1[CH:26]=[C:25](B(O)O)[C:24]([O:30][CH3:31])=[CH:23][C:22]=1[C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=1.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>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.O>[CH2:1]([S:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([C:25]3[C:24]([O:30][CH3:31])=[CH:23][C:22]([C:32]4[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[CH:33]=4)=[C:21]([Cl:20])[CH:26]=3)=[N:14][CH:15]=[N:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 86687599(2-Chloro-3'-fluoro-5-methoxy-[1,1'-biphenyl]-4-yl)boronic acidHCID 866877657-(Benzylthio)-4-chloroquinazoline

Product 1

HCID 866877667-(Benzylthio)-4-(2-chloro-3'-fluoro-5-methoxy-[1,1'-biphenyl]-4-yl)quinazoline

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

A microwave vial was charged with 7-(benzylthio)-4-chloroquinazoline (0.372 g, 1.298 mmol), (2-chloro-3′-fluoro-5-methoxy-[1,1′-biphenyl]-4-yl)boronic acid (0.364 g, 1.298 mmol), tetrakis(triphenylphosphine)palladium(0) (0.150 g, 0.130 mmol), and potassium carbonate (0.897 g, 6.49 mmol). Dioxane (3.24 ml) and Water (1.081 ml) were added; the vial was flushed with argon and sealed, and microwaved at 90° C. for 30 minutes. The reaction was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (RediSep Gold 12 g, gradient elution 0-75% EtOAc:Heptane) to afford 7-(benzylthio)-4-(2-chloro-3′-fluoro-5-methoxy-[1,1′-biphenyl]-4-yl)quinazoline as a yellow solid. (ESI) 487.1 (M+H)+.

Workup

  1. customthe vial was flushed with argon
  2. customsealed
  3. custommicrowaved at 90° C. for 30 minutes
  4. additionThe reaction was diluted with ethyl acetate
  5. washwashed with water
  6. extractionThe aqueous layer was extracted with ethyl acetate
  7. dry with materialthe combined organic layers were dried with sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe material was purified via column chromatography (RediSep Gold 12 g, gradient elution 0-75% EtOAc:Heptane)

Sources & evidence

ORD record
ord-d5208ed979c6471da06c4cfc537e9944
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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