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

HRID 1502340

반응식

HRID 1502340 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.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]

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)촉매HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

반응 조건

온도
120 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-ab3e2283fa6e47bda8eadfaab15250b6
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09206175B2

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