Cesium fluoride → ethyl 2-(8-(benzo[d]thiazol-2-yl((2-(trimethylsilyl)ethoxy)methyl)carbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(4-(hydroxymethyl)phenyl)thiazole-4-carboxylate

HRID 1518292ノート

反応式

HRID 1518292 の反応式
[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[N:10]([CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:40])[CH3:39])[C:11]([C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[CH2:21][N:20]([C:23]1[S:24][C:25](Br)=[C:26]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[N:27]=1)[CH2:19][CH2:18]2)=[O:12].[OH:42][CH2:43][C:44]1[CH:49]=[CH:48][C:47](B(O)O)=[CH:46][CH:45]=1.[F-].[Cs+]>COCCOC.CO.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>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[N:10]([CH2:34][O:35][CH2:36][CH2:37][Si:38]([CH3:41])([CH3:40])[CH3:39])[C:11]([C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[C:22]=1[CH2:21][N:20]([C:23]1[S:24][C:25]([C:47]3[CH:48]=[CH:49][C:44]([CH2:43][OH:42])=[CH:45][CH:46]=3)=[C:26]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[N:27]=1)[CH2:19][CH2:18]2)=[O:12]

参加物

7

反応物 3

HCID 25953Cesium fluorideHCID 27347064-(Hydroxymethyl)benzeneboronic acidHCID 59447650ethyl 2-(8-(benzo[d]thiazol-2-yl((2-(trimethylsilyl)ethoxy)methyl)carbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-bromothiazole-4-carboxylate

生成物 1

HCID 59447480ethyl 2-(8-(benzo[d]thiazol-2-yl((2-(trimethylsilyl)ethoxy)methyl)carbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-5-(4-(hydroxymethyl)phenyl)thiazole-4-carboxylate収率 60.6%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 887Methanol溶媒HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
110 °C

実験手順

A mixture of compound 34C (0.135 g, 0.2 mmol), 4-(hydroxymethyl)phenylboronic acid (0.033 g, 0.22 mmol), Pd(PPh3)4 (0.012 g, 0.01 mmol) and CsF (0.091 g, 0.6 mmol) in the DME (2 mL) and MeOH (1 mL) were heated under microwave conditions (110° C., 20 minutes). The reaction mixture was concentrated, and partitioned between water and EtOAc. The aqueous layer was extracted with additional EtOAc. The combined organic layers were washed with brine, dried (MgSO4), filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel eluting with 1:1/hexanes:EtOAc to provide 0.085 g of the desired product 34D, which was also a mixture of two regioisomers. MS (ESI(+)): m/z 701 (M+H).

後処理

  1. concentrationThe reaction mixture was concentrated
  2. custompartitioned between water and EtOAc
  3. extractionThe aqueous layer was extracted with additional EtOAc
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash column chromatography on silica gel eluting with 1:1/hexanes

出典と根拠

ORDレコード
ord-0e8f681b553043bfaada600ed8755e48
出典データセット
uspto-grants-2012_07
特許番号
US08232273B2

反応ノート

読み込み中…