Water → Methyl 5-(3-aminoisoquinolin-7-yl)-6-methylnicotinate

HRID 468919노트

반응식

HRID 468919 반응식
CC1(C)C(C)(C)OB([C:9]2[CH:18]=[C:17]3[C:12]([CH:13]=[C:14]([NH2:19])[N:15]=[CH:16]3)=[CH:11][CH:10]=2)O1.Br[C:22]1[CH:23]=[C:24]([C:29]([O:31][CH3:32])=[O:30])[CH:25]=[N:26][C:27]=1[CH3:28].C(=O)([O-])[O-].[K+].[K+].COCCOC.O>C(OCC)(=O)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[NH2:19][C:14]1[N:15]=[CH:16][C:17]2[C:12]([CH:13]=1)=[CH:11][CH:10]=[C:9]([C:22]1[C:27]([CH3:28])=[N:26][CH:25]=[C:24]([CH:23]=1)[C:29]([O:31][CH3:32])=[O:30])[CH:18]=2

참가 물질

8

반응물 5

HCID 962WaterHCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 58001778Methyl 5-bromo-6-methylnicotinateHCID 679762687-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-3-amine

생성물 1

HCID 67975074Methyl 5-(3-aminoisoquinolin-7-yl)-6-methylnicotinate수율 74%

시약·촉매·용매 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)촉매HCID 8857Ethyl Acetate용매

실험 절차

A mixture of 7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-3-amine (337.3 mg; 0.8742 mmol), methyl 5-bromo-6-methyl-pyridine-3-carboxylate (214.2 mg; 0.9311 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (63.3 mg; 0.0894 mmol), potassium carbonate (307.2 mg; 2.223 mmol), 1,2-dimethoxyethane (3.0 mL; 28 mmol), and water (0.3 mL; 20 mmol) was subjected to microwave irradiation at 110° C. for 90 minutes. The reaction mixture was diluted with ethyl acetate, washed with water and brine, dried over magnesium sulfate, filtered, and evaporated in vacuo. The crude product was purified via flash chromatography on silica gel (40 g silica, solvent gradient: 0-10% methanol in dichloromethane) to yield 189.8 mg (74%) of the title compound. LCMS (ESI): M+H=294.2; 1H NMR (400 MHz, DMSO) δ 8.98 (d, J=1.9 Hz, 1H), 8.88 (s, 1H), 8.10 (d, J=1.9 Hz, 1H), 7.88 (s, 1H), 7.62 (d, J=8.6 Hz, 1H), 7.54 (d, J=8.6 Hz, 1H), 6.67 (s, 1H), 6.03 (s, 2H), 3.90 (s, 3H), 2.57 (s, 3H).

후처리

  1. customirradiation at 110° C. for 90 minutes
  2. washwashed with water and brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe crude product was purified via flash chromatography on silica gel (40 g silica, solvent gradient: 0-10% methanol in dichloromethane)

출처 및 근거

ORD 기록
ord-0231f21ea1d9415ca8d11eedb8c12cb8
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08623889B2

반응 노트

불러오는 중…