Potassium Carbonate → HCID 86687673, compound

HRID 1473609Notes

Reaction equation

HRID 1473609 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]([OH:32])=[CH:4][N:3]=1.[F:33][C:34]1[CH:39]=[CH:38][C:37](B(O)O)=[C:36]([O:43][CH3:44])[CH:35]=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>[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:37]1[CH:38]=[CH:39][C:34]([F:33])=[CH:35][C:36]=1[O:43][CH3:44])=[N:3][CH:4]=[C:5]2[OH:32])(=[O:14])=[O:13]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 2782672(4-Fluoro-2-methoxyphenyl)boronic acidHCID 86687509HCID 86687509, compound

Product 1

HCID 86687673HCID 86687673, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

A microwave vial was charged with 1-chloro-N-(2,4-dimethoxybenzyl)-4-hydroxy-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (INTERMEDIATE WWW) (0.263 g, 0.535 mmol), (4-fluoro-2-methoxyphenyl)boronic acid (0.136 g, 0.802 mmol), tetrakis(triphenylphosphine)palladium(0) (0.062 g, 0.053 mmol), and potassium carbonate (0.369 g, 2.67 mmol). Dioxane (2.67 ml) and Water (0.891 ml) were added, the vial was flushed with argon and sealed, and microwaved 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 column chromatography (RediSep Gold 12 g, gradient elution 0-100% EtOAc:Heptane) to afford N-(2,4-dimethoxybenzyl)-1-(4-fluoro-2-methoxyphenyl)-4-hydroxy-N-(thiazol-2-yl)isoquinoline-6-sulfonamide. (ESI) 582.2 (M+H)+.

Workup

  1. customthe vial was flushed with argon
  2. customsealed
  3. custommicrowaved at 100° 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 0-100% EtOAc:Heptane)

Sources & evidence

ORD record
ord-dd6c347e4b2546ff8ab856d214cb577e
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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