Cesium carbonate → 1-(2-methoxy-4-methylphenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

HRID 1473432Notes

Reaction equation

HRID 1473432 reaction equation
C([O-])([O-])=O.[Cs+].[Cs+].[CH3:7][O:8][C:9]1[CH:14]=[C:13]([CH3:15])[CH:12]=[CH:11][C:10]=1B(O)O.Cl[C:20]1[C:29]2[C:24](=[CH:25][C:26]([S:30]([N:33](CC3C=CC(OC)=CC=3)[C:34]3[S:35][CH:36]=[CH:37][N:38]=3)(=[O:32])=[O:31])=[CH:27][CH:28]=2)[CH:23]=[CH:22][N:21]=1>COCCOC.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>[CH3:7][O:8][C:9]1[CH:14]=[C:13]([CH3:15])[CH:12]=[CH:11][C:10]=1[C:20]1[C:29]2[C:24](=[CH:25][C:26]([S:30]([NH:33][C:34]3[S:35][CH:36]=[CH:37][N:38]=3)(=[O:32])=[O:31])=[CH:27][CH:28]=2)[CH:23]=[CH:22][N:21]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 18414543(2-Methoxy-4-methylphenyl)boronic acidHCID 866874151-Chloro-N-(4-methoxybenzyl)-N-(thiazol-2-YL)isoquinoline-6-sulfonamide

Product 1

HCID 715854311-(2-methoxy-4-methylphenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamideYield 51%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A microwave vial containing Cs2CO3 (0.175 g, 0.538 mmol), (2-methoxy 4-methyl phenyl)boronic acid (27 mg, 0.175 mmol) and 1-chloro-N-(4-methoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (Intermediate JJJ; 0.06 g, 0.135 mmol) in DME (1.500 ml) and water (0.225 ml) was purged with nitrogen and Pd(PPh3)4(0.016 g, 0.013 mmol) was added and the reaction was irradiated under microwave irradiation at 125° C. for 1.5 h. The aqueous layer was discarded and the organic layer was concentrated. To this was then added DCM (1 mL) and TFA (0.5 mL) and the reaction was shaken for 2 h. The reaction mixture was purified by reverse-phase chromatography with 0.1% NH4OH in ACN and water as mobile phase to obtain 1-(2-methoxy-4-methylphenyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (28 mg, 51%) as a light yellow solid. 1H NMR (500 MHz, DMSO-d6) δ ppm 12.87 (br. s., 1H) 8.65 (d, J=5.61 Hz, 1H) 8.51 (s, 1H) 8.05 (d, J=5.73 Hz, 1H) 7.85 (dd, J=8.88, 1.66 Hz, 1H) 7.71 (d, J=8.94 Hz, 1H) 7.27 (d, J=4.58 Hz, 1H) 7.20 (d, J=7.56 Hz, 1H) 7.04 (s, 1H) 6.93 (d, J=7.45 Hz, 1H) 6.87 (d, J=4.58 Hz, 1H) 3.63 (s, 3H) 2.43 (s, 3H); m/z (ESI) 416.0 (M+H)+.

Workup

  1. additionwas added
  2. customthe reaction was irradiated under microwave irradiation at 125° C. for 1.5 h
  3. concentrationthe organic layer was concentrated
  4. customThe reaction mixture was purified by reverse-phase chromatography with 0.1% NH4OH in ACN and water as mobile phase

Sources & evidence

ORD record
ord-317a995dc86b4ff39c26641871bf6af6
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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