Cesium carbonate → N-(7-(5-methoxy-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide

HRID 468792

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HRID 468792 반응식
CC1(C)C(C)(C)OB([C:9]2[CH:18]=[C:17]3[C:12]([CH:13]=[C:14]([NH:19][C:20]([CH:22]4[CH2:24][CH2:23]4)=[O:21])[N:15]=[CH:16]3)=[CH:11][CH:10]=2)O1.Br[C:27]1[CH:32]=[C:31]([O:33][CH3:34])[CH:30]=[CH:29][C:28]=1[CH3:35].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:34][O:33][C:31]1[CH:30]=[CH:29][C:28]([CH3:35])=[C:27]([C:9]2[CH:18]=[C:17]3[C:12]([CH:13]=[C:14]([NH:19][C:20]([CH:22]4[CH2:23][CH2:24]4)=[O:21])[N:15]=[CH:16]3)=[CH:11][CH:10]=2)[CH:32]=1

참가 물질

6

반응물 3

HCID 10796Cesium carbonateHCID 5202882-Bromo-4-methoxy-1-methylbenzeneHCID 67976378N-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-3-yl)cyclopropanecarboxamide

생성물 1

HCID 68095312N-(7-(5-methoxy-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide수율 21.7%

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 218864351,4-Dioxane--water (1/1)용매

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온도
130 °C

실험 절차

To a solution of N-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-3-yl)cyclopropanecarboxamide (200 mg, 0.59 mmol) in dioxane/water (5.0 ml) were added 2-bromo-4-methoxy-1-methylbenzene (100 mg, 0.50 mmol), cesium carbonate (391 mg, 1.2 mmol) and [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (22 mg, 0.03 mmol). It was purged with nitrogen and heated at 130° C. for 30 min under microwave irradiation. The reaction mixture was concentrated, washed with water and extracted with ethyl acetate. It was dried over sodium sulfate, concentrated and purified by pre-HPLC to give the product (36 mg, 18.4%). LCMS (ESI): RT (min)=1.214, M+H+=332.9, method=A; 1H NMR (400 MHz, DMSO-d6) δ 9.17 (s, 1H), 8.49 (s, 1H), 8.00 (s, 1H), 7.90 (d, J=8.8 Hz, 1H), 7.70-7.68 (m, 1H), 7.24 (d, J=8.4 Hz, 1H), 6.91-6.86 (m, 2H), 3.76 (s, 3H), 2.19 (s, 3H), 2.09-2.05 (m, 1H), 0.87-0.81 (m, 4H).

후처리

  1. customIt was purged with nitrogen
  2. concentrationThe reaction mixture was concentrated
  3. washwashed with water
  4. extractionextracted with ethyl acetate
  5. dry with materialIt was dried over sodium sulfate
  6. concentrationconcentrated
  7. custompurified by pre-HPLC

출처 및 근거

ORD 기록
ord-c3e7206cbe3a484b89c4f44801219019
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08623889B2

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