Potassium Carbonate → HCID 136409072, compound

HRID 1473606Notes

Reaction equation

HRID 1473606 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.[OH:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=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:35]1[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=1[OH:33])=[N:3][CH:4]=[C:5]2[F:32])(=[O:13])=[O:14]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 2773454(2-Hydroxyphenyl)boronic acidHCID 86687426HCID 86687426, compound

Product 1

HCID 136409072HCID 136409072, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

A microwave vial was charged with 1-chloro-N-(2,4-dimethoxybenzyl)-4-fluoro-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (Intermediate PPP; 0.075 g, 0.152 mmol), (2-hydroxyphenyl)boronic acid (0.031 g, 0.228 mmol), tetrakis(triphenylphosphine)palladium(0) (0.018 g, 0.015 mmol), and potassium carbonate (0.105 g, 0.759 mmol). Dioxane (0.759 mL) and Water (0.253 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)-4-fluoro-1-(2-hydroxyphenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide. (ESI) 522.2 (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-a6aa1ace9599477d94352d0a7c3c447b
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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