Sodium Carbonate → N-(7-(2-cyano-5-hydroxyphenyl)isoquinolin-3-yl)cyclopropanecarboxamide

HRID 468822

反応式

HRID 468822 の反応式
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.Cl[C:27]1[CH:34]=[C:33]([OH:35])[CH:32]=[CH:31][C:28]=1[C:29]#[N:30].C(=O)([O-])[O-].[Na+].[Na+]>C(#N)C.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>[C:29]([C:28]1[CH:27]=[CH:34][C:33]([OH:35])=[CH:32][C:31]=1[C:9]1[CH:18]=[C:17]2[C:12]([CH:13]=[C:14]([NH:19][C:20]([CH:22]3[CH2:23][CH2:24]3)=[O:21])[N:15]=[CH:16]2)=[CH:11][CH:10]=1)#[N:30]

参加物

7

反応物 3

HCID 10340Sodium CarbonateHCID 5927972-Chloro-4-hydroxybenzonitrileHCID 67976378N-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-3-yl)cyclopropanecarboxamide

生成物 1

HCID 67974908N-(7-(2-cyano-5-hydroxyphenyl)isoquinolin-3-yl)cyclopropanecarboxamide収率 91.1%

試薬・触媒・溶媒 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)触媒HCID 6342Acetonitrile溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
120 °C

実験手順

A mixture of N-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoquinolin-3-yl)cyclopropanecarboxamide (48 mg, 0.1 mmol), 2-chloro-4-hydroxybenzonitrile (45 mg, 0.3 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (10 mg, 0.015 mmol), and saturated aqueous sodium carbonate (0.1 mL) in acetonitrile (1 mL) was heated under microwave irradiation (Biotage, 200 watts) at 120° C. for 20 minutes. The cooled reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (50 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was purified by reverse phase HPLC (5-85% acetonitrile in water with 0.1% formic acid over 14 min) to afford the title compound as an off-white solid (30 mg, 60%). 1H NMR (400 MHz, DMSO) δ 10.98 (s, 1H), 10.95-10.68 (brs, 1H), 9.23 (s, 1H), 8.52 (s, 1H), 8.22 (s, 1H), 7.99 (d, J=8.6 Hz, 1H), 7.84 (d, J=8.6 Hz, 1H), 7.80 (d, J=8.5 Hz, 1H), 7.03 (d, J=2.1 Hz, 1H), 6.97 (dd, J=8.5, 2.2 Hz, 1H), 2.14-2.03 (m, 1H), 0.94-0.77 (m, 4H). LCMS (Method E): RT=4.137 min, M+H+=330.1.

後処理

  1. customThe cooled reaction mixture
  2. washwashed with water (50 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customto afford a residue that
  8. customwas purified by reverse phase HPLC (5-85% acetonitrile in water with 0.1% formic acid over 14 min)

出典と根拠

ORDレコード
ord-776c475ff6484669b4647fc2df8ecdd4
出典データセット
uspto-grants-2014_01
特許番号
US08623889B2

関連ノート

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