Potassium Carbonate → HCID 86687489, compound

HRID 1473444Notes

Reaction equation

HRID 1473444 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([S:12]([N:15]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:23]=3[O:30][CH3:31])[C:16]3[S:17][CH:18]=[CH:19][N:20]=3)(=[O:14])=[O:13])=[CH:9][CH:10]=2)[C:5]([F:32])=[CH:4][N:3]=1.[CH3:33][O:34][C:35]1[CH:40]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:38]=[CH:37][C:36]=1B(O)O.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>[CH3:31][O:30][C:23]1[CH:24]=[C:25]([O:28][CH3:29])[CH:26]=[CH:27][C:22]=1[CH2:21][N:15]([C:16]1[S:17][CH:18]=[CH:19][N:20]=1)[S:12]([C:8]1[CH:7]=[C:6]2[C:11](=[CH:10][CH:9]=1)[C:2]([C:36]1[CH:37]=[CH:38][C:39]([C:41]([F:44])([F:43])[F:42])=[CH:40][C:35]=1[O:34][CH3:33])=[N:3][CH:4]=[C:5]2[F:32])(=[O:14])=[O:13]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 24901776(2-Methoxy-4-(trifluoromethyl)phenyl)boronic acidHCID 86687426HCID 86687426, compound

Product 1

HCID 86687489HCID 86687489, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A microwave vial was charged with 1-chloro-N-(2,4-dimethoxybenzyl)-4-fluoro-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (Intermediate PPP; 0.041 g, 0.083 mmol), (2-methoxy-4-(trifluoromethyl)phenyl)boronic acid (0.027 g, 0.125 mmol), Pd(PPh3)4 (9.59 mg, 8.30 μmol), and potassium carbonate (0.057 g, 0.415 mmol). Dioxane (0.415 mL) and water (0.138 mL) were added, the vial was flushed with argon and sealed, and heated in a microwave reactor at 100° 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 silica gel chromatography (12 g, gradient elution 0 to 100% EtOAc:Heptane) to afford N-(2,4-dimethoxybenzyl)-4-fluoro-1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide. The material was dissolved in DCM and TFA (0.1 mL, 1.298 mmol) was added. The reaction was stirred for 30 minutes at room temperature after which time the reaction was concentrated and triturated with diethyl ether. The solids were filtered, washed with diethyl ether, and vacuum dried to afford 4-fluoro-1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (0.008 g, 0.017 mmol, 19.94% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm=13.00 (s, 1H), 8.74 (d, J=1.6 Hz, 1H), 8.51 (d, J=1.4 Hz, 1H), 7.99 (dd, J=1.7, 8.9 Hz, 1H), 7.79 (dd, J=1.8, 9.0 Hz, 1H), 7.61-7.55 (m, 1H), 7.55-7.46 (m, 2H), 7.31 (d, J=4.6 Hz, 1H), 6.90 (d, J=4.6 Hz, 1H), 3.75 (s, 3H). m/z (ESI) 484.2 (M+H)+.

Workup

  1. customthe vial was flushed with argon
  2. customsealed
  3. additionThe reaction was diluted with ethyl acetate
  4. washwashed with water
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. dry with materialthe combined organic layers were dried with sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe material was purified via silica gel chromatography (12 g, gradient elution 0 to 100% EtOAc:Heptane)

Sources & evidence

ORD record
ord-6b4ba11d3ff64c979d0491abb4e7875c
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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