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

HRID 1473434노트

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HRID 1473434 반응식
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

참가 물질

7

반응물 3

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

생성물 1

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

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

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온도
125 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-10a1344219bf4cb6846b204825df1d59
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09012443B2

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