Lithium aluminum hydride → N-(7-(1-hydroxy-2-methylpropan-2-yloxy)isoquinolin-3-yl)cyclopropanecarboxamide

HRID 1502286Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1502286
[CH:1]1([C:4]([NH:6][C:7]2[N:8]=[CH:9][C:10]3[C:15]([CH:16]=2)=[CH:14][CH:13]=[C:12]([O:17][C:18]([CH3:25])([CH3:24])[C:19](OCC)=[O:20])[CH:11]=3)=[O:5])[CH2:3][CH2:2]1.[AlH4-].[Li+]>O1CCCC1>[OH:20][CH2:19][C:18]([CH3:25])([O:17][C:12]1[CH:11]=[C:10]2[C:15]([CH:16]=[C:7]([NH:6][C:4]([CH:1]3[CH2:3][CH2:2]3)=[O:5])[N:8]=[CH:9]2)=[CH:14][CH:13]=1)[CH3:24]

Komponenten

4

Edukt 2

HCID 28112Lithium aluminum hydrideHCID 67974885Ethyl 2-(3-(cyclopropanecarboxamido)isoquinolin-7-yloxy)-2-methylpropanoate

Produkt 1

HCID 57410975N-(7-(1-hydroxy-2-methylpropan-2-yloxy)isoquinolin-3-yl)cyclopropanecarboxamideAusbeute 9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a solution of ethyl 2-(3-(cyclopropanecarboxamido)isoquinolin-7-yloxy)-2-methylpropanoate (63.4 mg, 0.185 mmol) in tetrahydrofuran (3 mL, 40 mmol) was added 1.0 M of lithium tetrahydroaluminate in tetrahydrofuran (0.20 mL). The reaction mixture was stirred at room temperature for 1 hour. The reaction was quenched by sequential addition of 9 μL water, then 9 μL 15% aq NaOH, then 26 μL water. The resulting mixture was stirred at room temperature for 15 minutes, then diluted with dichloromethane, dried with MgSO4, filtered through celite, and evaporated in vacuo. The crude product was purified via reverse phase HPLC and lyophilized to yield 4.8 mg (9%) of N-(7-(1-hydroxy-2-methylpropan-2-yloxy)isoquinolin-3-yl)cyclopropanecarboxamide. LCMS (ESI): RT (min)=3.414, M+H=301.1, method=E; 1H NMR (400 MHz, DMSO-d6) δ 10.77 (s, 1H), 9.03 (s, 1H), 8.38 (s, 1H), 7.76 (d, J=8.9 Hz, 1H), 7.61 (d, J=2.0 Hz, 1H), 7.39 (dd, J=8.9, 2.3 Hz, 1H), 4.93 (t, J=5.6 Hz, 1H), 3.45 (d, J=5.7 Hz, 2H), 3.27 (s, overlapping water non-integratable), 2.12-1.97 (m, 1H), 0.83 (dt, J=10.1, 5.4 Hz, 4H).

Aufarbeitung

  1. customThe reaction was quenched by sequential addition of 9 μL water
  2. stirringThe resulting mixture was stirred at room temperature for 15 minutes
  3. additiondiluted with dichloromethane
  4. dry with materialdried with MgSO4
  5. filtrationfiltered through celite
  6. customevaporated in vacuo
  7. customThe crude product was purified via reverse phase HPLC

Quellen und Nachweise

ORD-Eintrag
ord-e110a4c444ac40d6844bb4b60af5f637
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09206175B2

Notizen zur Reaktion

Wird geladen…