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

HRID 1502286Notes

Reaction equation

HRID 1502286 reaction equation
[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]

Participants

4

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-e110a4c444ac40d6844bb4b60af5f637
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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