Potassium Carbonate → HCID 86687545, compound

HRID 1473490Notes

Reaction equation

HRID 1473490 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][C:8]([S:12]([N:15](CC3C=CC(OC)=CC=3)[C:16]3[S:17][CH:18]=[CH:19][N:20]=3)(=[O:14])=[O:13])=[CH:9][CH:10]=2)[CH:5]=[N:4][CH:3]=1.[CH3:30][O:31][C:32]1[CH:37]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:35]=[CH:34][C:33]=1B(O)O.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>CCOC(C)=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.O>[CH3:30][O:31][C:32]1[CH:37]=[C:36]([C:38]([F:39])([F:40])[F:41])[CH:35]=[CH:34][C:33]=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:14])=[O:13])=[CH:9][CH:10]=2)[CH:5]=[N:4][CH:3]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 24901776(2-Methoxy-4-(trifluoromethyl)phenyl)boronic acidHCID 86687470HCID 86687470, compound

Product 1

HCID 86687545HCID 86687545, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A microwave vial charged with 4-bromo-N-(4-methoxybenzyl)-N-(thiazol-2-yl)isoquinoline-7-sulfonamide (Intermediate PPPP) (0.066 g, 0.135 mmol), 2-methoxy-4-(trifluoromethyl)phenylboronic acid (Combi-Blocks, San Diego, Calif.) (0.044 g, 0.202 mmol), potassium carbonate (0.093 g, 0.673 mmol), dioxane (0.673 ml) and water (0.224 ml) was purged with argon prior to the addition of Pd(PPh3)4 (0.016 g, 0.013 mmol). The vessel was sealed and irradiated at 100° C. for 30 min. The resulting mixture was diluted with EtOAc and extracted with water, the aqueous phase was extracted with EtOAc and the combined organics were dried under reduced pressure. To the crude brown oil was added DCM (3 ml) and TFA (1 ml) and the resulting solution stirred overnight at RT affording conversion to desired product. The mixture was dried under reduced pressure and purified with a 25 g HP spherical silica gel (Interchim, Mouintlucon, France, 15 μm) ramping EtOAc in heptane (0 to 50%, 10% DCM isocratic throughout) providing product as a film which was lyophilized from MeOH/H2O to provide 4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)isoquinoline-7-sulfonamide (38 mg, 0.082 mmol, 60.7% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 6.87 (d, J=4.60 Hz, 1H) 7.28 (d, J=4.60 Hz, 1H) 7.46-7.53 (m, 2H) 7.54-7.59 (m, 1H) 7.61 (d, J=8.90 Hz, 1H) 8.02 (dd, J=8.85, 1.91 Hz, 1H) 8.53 (s, 1H) 8.75 (d, J=1.56 Hz, 1H) 9.55-9.66 (m, 1H) 12.88 (br. s., 1H). m/z (ESI) 466.2 (M+H)+.

Workup

  1. customwas purged with argon
  2. customThe vessel was sealed
  3. customirradiated at 100° C. for 30 min
  4. extractionextracted with water
  5. extractionthe aqueous phase was extracted with EtOAc
  6. customthe combined organics were dried under reduced pressure
  7. additionTo the crude brown oil was added DCM (3 ml) and TFA (1 ml)

Sources & evidence

ORD record
ord-567db960ae7e46a69707b744e66351a1
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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