Cesium carbonate → 1-(4-fluoro-2-hydroxyphenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide

HRID 1473434Notes

Reaction equation

HRID 1473434 reaction equation
C([O-])([O-])=O.[Cs+].[Cs+].[F:7][C:8]1[CH:13]=[CH:12][C:11](B(O)O)=[C:10]([OH:17])[CH:9]=1.Cl[C:19]1[C:28]2[C:23](=[CH:24][C:25]([S:29]([N:32]([CH2:38][C:39]3[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=3)[C:33]3[S:34][CH:35]=[CH:36][N:37]=3)(=[O:31])=[O:30])=[CH:26][CH:27]=2)[CH:22]=[CH:21][N:20]=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>[F:7][C:8]1[CH:13]=[CH:12][C:11]([C:19]2[C:28]3[C:23](=[CH:24][C:25]([S:29]([N:32]([CH2:38][C:39]4[CH:44]=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=4)[C:33]4[S:34][CH:35]=[CH:36][N:37]=4)(=[O:30])=[O:31])=[CH:26][CH:27]=3)[CH:22]=[CH:21][N:20]=2)=[C:10]([OH:17])[CH:9]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 3865312(4-Fluoro-2-hydroxy)phenylboronic acidHCID 866874151-Chloro-N-(4-methoxybenzyl)-N-(thiazol-2-YL)isoquinoline-6-sulfonamide

Product 1

HCID 1364090671-(4-fluoro-2-hydroxyphenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamideYield 92.4%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
125 °C

Procedure

A vial containing a suspension of Cs2CO3 (0.292 g, 0.897 mmol), (4-fluoro-2-hydroxyphenyl)boronic acid (0.045 g, 0.292 mmol) and 1-chloro-N-(4-methoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (Intermediate JJJ; 0.1 g, 0.224 mmol) in DME (2.5 ml) and water (0.375 ml) was degassed with nitrogen and tetrakis(triphenylphosphine)palladium (0.026 g, 0.022 mmol) was added. The vial was sealed and heated under microwave irradiation at 125° C. for 30 min. The aqueous layer was discarded using a pipette and the organic layer was concentrated and purified by silica gel chromatography (25 g column, eluting with Hex:EtOAc (0 to 50%)). Pure fractions were combined and concentrated to obtain 1-(4-fluoro-2-hydroxyphenyl)-N-(4-methoxybenzyl)-N-(thiazol-2-yl)isoquinoline-6-sulfonamide (0.108 g, 0.207 mmol, 92% yield) as light yellow solid.

Workup

  1. additionA vial containing
  2. additionwas added
  3. customThe vial was sealed
  4. concentrationthe organic layer was concentrated
  5. custompurified by silica gel chromatography (25 g column, eluting with Hex:EtOAc (0 to 50%))
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-10a1344219bf4cb6846b204825df1d59
Source dataset
uspto-grants-2015_04
Patent number
US09012443B2

Reaction notes

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