Potassium Carbonate → HCID 86687780, compound

HRID 1473695Notes

Reaction equation

HRID 1473695 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([S:12]([N:15](CC3C=CC(OC)=CC=3OC)[C:16]3[S:17][CH:18]=[CH:19][N:20]=3)(=[O:14])=[O:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[Cl:32][C:33]1[CH:38]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:36]=[CH:35][C:34]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.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>[Cl:32][C:33]1[CH:38]=[C:37]([C:39]([F:40])([F:41])[F:42])[CH:36]=[CH:35][C:34]=1[C:2]1[C:11]2[C:6](=[CH:7][C:8]([S:12]([NH:15][C:16]3[S:17][CH:18]=[CH:19][N:20]=3)(=[O:13])=[O:14])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 2783251[2-Chloro-4-(trifluoromethyl)phenyl]boronic acidHCID 86687456HCID 86687456, compound

Product 1

HCID 86687780HCID 86687780, compoundYield 23.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a mixture of 4-chloro-N-(2,4-dimethoxybenzyl)-N-(thiazol-2-yl)quinazoline-7-sulfonamide (Intermediate KKKK; 0.07 g, 0.147 mmol), (2-chloro-4-(trifluoromethyl)phenyl)boronic acid (0.049 mg, 0.220 mmol) and potassium carbonate (0.101 g, 0.734 mmol) in Dioxane (Solvent Ratio: 3, Solvent Volume: 0.734 ml) and Water (Solvent Ratio: 1.000, Solvent Volume: 0.245 ml) was added Pd (PPh3)4 (17 mg, 0.015 mmol), degassed with nitrogen and irradiated in microwave at 100° C. for 1 h. The aqueous layer was discarded and the reaction mixture was filtered through SPE and concentrated. To this was then added DCM (1 ml) and TFA (1 ml) and the reaction was stirred for 2 h. The crude mixture was purified using reverse phase HPLC to obtain 4-(2-chloro-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)quinazoline-7-sulfonamide (16 mg, 23% yield) as white solid. m/z (ESI) 470.0 (M+H)+.

Workup

  1. customdegassed with nitrogen
  2. customirradiated in microwave at 100° C. for 1 h
  3. filtrationthe reaction mixture was filtered through SPE and
  4. concentrationconcentrated
  5. customThe crude mixture was purified

Sources & evidence

ORD record
ord-17d30062ba4e4621bc9a6a84162494ee
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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