Potassium Phosphate, Tribasic → 7-(3-Difluoromethylphenyl)-isoquinoline-5-sulfonic acid (2-amino-ethyl)-amide

HRID 269986노트

반응식

HRID 269986 반응식
C(OC(=O)[NH:7][CH2:8][CH2:9][NH:10][S:11]([C:14]1[C:15]2[CH:16]=[CH:17][N:18]=[CH:19][C:20]=2[CH:21]=[C:22](Br)[CH:23]=1)(=[O:13])=[O:12])(C)(C)C.[F:26][CH:27]([F:37])[C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.CO.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]>[NH2:7][CH2:8][CH2:9][NH:10][S:11]([C:14]1[C:15]2[CH:16]=[CH:17][N:18]=[CH:19][C:20]=2[CH:21]=[C:22]([C:32]2[CH:31]=[CH:30][CH:29]=[C:28]([CH:27]([F:37])[F:26])[CH:33]=2)[CH:23]=1)(=[O:12])=[O:13]

참가 물질

7

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 447172443-Difluoromethyl-phenylboronic acidHCID 58816140[2-(7-Bromo-isoquinoline-5-sulfonylamino)-ethyl]-carbamic acid tert-butyl ester

생성물 1

HCID 112803467-(3-Difluoromethylphenyl)-isoquinoline-5-sulfonic acid (2-amino-ethyl)-amide수율 88.3%

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 86595564Dimethoxyethane methanol용매

반응 조건

온도
82 °C

실험 절차

Dissolve [2-(7-bromo-isoquinoline-5-sulfonylamino)-ethyl]-carbamic acid tert-butyl ester (0.13 g, 0.30 mmol) and 3-(difluoromethyl)phenylboronic acid (0.057 g, 0.33 mmol) in DME-methanol (8:1, 10 ml). To the mixture, add K3PO4 (0.13 g, 0.60 mmol), and PdCl2(dppf) (0.012 g, 0.015 mmol). Heat this mixture at 82° C. overnight. Cool the reaction mixture, dilute with water and extract with EtOAc. Wash with brine and evaporate to dryness. Purify by silica gel chromatography to give the desired compound (0.10 g, 71% yield): 1H NMR (CDCl3): δ9.39 (s, 1H), 8.66 (m, 2H), 8.43 (d, J=5.7 Hz, 2H), 7.86 (m, 2H), 7.61 (m, 2H), 6.76 (t, J=52.1 Hz, 1H), 5.00 (br s, 1H), 3.18 (m, 2H), 3.03 (m, 2H), 1.37 (s, 9H); ESIMS: m/z 478 (M+H)+.

후처리

  1. temperatureCool the reaction mixture
  2. extractionextract with EtOAc
  3. washWash with brine
  4. customevaporate to dryness
  5. customPurify by silica gel chromatography

출처 및 근거

ORD 기록
ord-1c02f53ad4f34396a0e03e34fad62472
출처 데이터셋
uspto-grants-2008_11
특허 번호
US07449477B2

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