Lithium aluminum hydride → HCID 67974857, compound

HRID 1502281Notes

Reaction equation

HRID 1502281 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]([C:17]2[C:18]([CH3:27])=[N:19][CH:20]=[C:21]([CH:26]=2)[C:22](OC)=[O:23])[CH:11]=3)=[O:5])[CH2:3][CH2:2]1.[AlH4-].[Li+]>O1CCCC1>[OH:23][CH2:22][C:21]1[CH:26]=[C:17]([C:12]2[CH:11]=[C:10]3[C:15]([CH:16]=[C:7]([NH:6][C:4]([CH:1]4[CH2:3][CH2:2]4)=[O:5])[N:8]=[CH:9]3)=[CH:14][CH:13]=2)[C:18]([CH3:27])=[N:19][CH:20]=1

Participants

4

Reactant 2

HCID 28112Lithium aluminum hydrideHCID 71115058HCID 71115058, compound

Product 1

HCID 67974857HCID 67974857, compoundYield 41%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of Methyl 5-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-6-methylnicotinate (11.9 mg, 0.0329 mmol) in tetrahydrofuran (3 mL, 40 mmol) was added 1.0 M of lithium tetrahydroaluminate in tetrahydrofuran (0.10 mL). The reaction mixture was stirred at room temperature for 30 minutes. The reaction was then quenched with water and extracted twice with dichloromethane. The combined organic extracts were dried over MgSO4, filtered, and evaporated in vacuo. The crude material was purified via flash chromatography on silica gel (25 g silica, solvent gradient: 0-10% methanol in dichloromethane) to yield 4.5 mg (41%) of N-(7-(5-(hydroxymethyl)-2-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide. LCMS (ESI): RT (Min)=2.995, M+H=334.1, method=E; 1H NMR (400 MHz, DMSO-d6) δ 10.91 (s, 1H), 9.19 (s, 1H), 8.50 (s, 1H), 8.46 (s, 1H), 8.06 (s, 1H), 7.95 (d, J=8.7 Hz, 1H), 7.74 (d, J=8.6 Hz, 1H), 7.64 (s, 1H), 5.30 (t, J=5.4 Hz, 1H), 4.58 (d, J=5.2 Hz, 2H), 2.47 (s, 3H), 2.08 (s, 1H), 0.91-0.78 (m, 4H).

Workup

  1. customThe reaction was then quenched with water
  2. extractionextracted twice with dichloromethane
  3. dry with materialThe combined organic extracts were dried over MgSO4
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe crude material was purified via flash chromatography on silica gel (25 g silica, solvent gradient: 0-10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-237846ef8e0145c68752c88a15178634
Source dataset
uspto-grants-2015_12
Patent number
US09206175B2

Reaction notes

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