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

HRID 269986ノート

反応式

HRID 269986 の反応式
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]

参加物

7

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 86595564Dimethoxyethane methanol溶媒

反応条件

温度
82 °C

実験手順

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)+.

後処理

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

出典と根拠

ORDレコード
ord-1c02f53ad4f34396a0e03e34fad62472
出典データセット
uspto-grants-2008_11
特許番号
US07449477B2

反応ノート

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