Chloroform → HCID 66690861, compound

HRID 403542Notes

Reaction equation

HRID 403542 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[C:9]2[CH:19]([N:21]([CH3:35])[S:22]([C:25]2[CH:30]=[CH:29][C:28]([C:31]([CH3:34])([CH3:33])[CH3:32])=[CH:27][CH:26]=2)(=[O:24])=[O:23])[CH3:20])=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[C:42]1(B(O)O)[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)(Cl)Cl>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:2]1([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH:7]=[CH:6][C:5]([N:8]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[C:9]2[CH:19]([N:21]([CH3:35])[S:22]([C:25]2[CH:30]=[CH:29][C:28]([C:31]([CH3:34])([CH3:33])[CH3:32])=[CH:27][CH:26]=2)(=[O:24])=[O:23])[CH3:20])=[CH:4][CH:3]=1

Participants

7

Reactant 5

HCID 6212ChloroformHCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 66827Phenylboronic AcidHCID 66688745HCID 66688745, compound

Product 1

HCID 66690861HCID 66690861, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
70 °C

Procedure

An oven-dried flask charged with N-{1-[3-(4-bromophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl]ethyl}-4-tert-butyl-N-methylbenzenesulfonamide (103 mg, 0.19 mmol) was diluted with 2 mL of a nitrogen-purged solution of DME/H2O (1:1). The resulting reaction mixture was then treated with K2CO3 (78.8 mg, 0.57 mmol) and phenyl boronic acid (46.3 mg, 0.38 mmol) at room temperature under a nitrogen atmosphere. In a separate oven dried vial containing triphenyl phosphine (43.9 mg, 0.17 mmol) and Pd2 dba3:CHCl3 (17 mg, 0.019 mmol) was placed 1 mL of the nitrogen purged DME/H2O solution (1:1). The contents of the vial were stirred until the Pd(0) was completely dissolved. The premixed palladium solution was then added to the reaction mixture and heated to 70° C. under nitrogen for 16 h. The reaction mixture was cooled to room temperature and concentrated under vacuum. The resulting residue was then taken up in EtOAc and filtered through a plug of silica. The filtrate was concentrated under vacuum to afford a crude residue that was purified by chromatography (silica gel, 0-75% EtOAC:Hex) to afford the desired product as a white solid (74 mg, 71% yield). 1H-NMR (CDCl3): δ 8.26 (d, 1H), 7.88 (d, 1H), 7.76 (d, 1H), 7.67 (m, 4H), 7.45 (m, 7H), 7.23 (m, 3H), 4.99 (q, 1H), 3.20 (s, 3H), 1.33 (d, 3H), 1.16 (s, 9H); MS (ESI) 552 (MH+).

Workup

  1. additionwas diluted with 2 mL of a nitrogen-
  2. custompurged solution of DME/H2O (1:1)
  3. customThe resulting reaction mixture
  4. customIn a separate oven dried vial
  5. custompurged DME/H2O solution (1:1)
  6. dissolutionwas completely dissolved
  7. additionThe premixed palladium solution was then added to the reaction mixture
  8. temperatureThe reaction mixture was cooled to room temperature
  9. concentrationconcentrated under vacuum
  10. filtrationfiltered through a plug of silica
  11. concentrationThe filtrate was concentrated under vacuum
  12. customto afford a crude residue that
  13. customwas purified by chromatography (silica gel, 0-75% EtOAC:Hex)

Sources & evidence

ORD record
ord-6f4d296c47624867beb883e1dcecee75
Source dataset
uspto-grants-2014_06
Patent number
US08748440B2

Reaction notes

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