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 1518292노트

반응식

HRID 1518292 반응식
[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]

참가 물질

7

반응물 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

생성물 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-carboxylate수율 60.6%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 887Methanol용매HCID 80711,2-Dimethoxyethane용매

반응 조건

온도
110 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-0e8f681b553043bfaada600ed8755e48
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08232273B2

반응 노트

불러오는 중…