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

HRID 1473434ノート

反応式

HRID 1473434 の反応式
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

参加物

7

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
125 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-10a1344219bf4cb6846b204825df1d59
出典データセット
uspto-grants-2015_04
特許番号
US09012443B2

反応ノート

読み込み中…