Aluminium lithium hydride → HCID 131725929, compound

HRID 2213140Notes

Reaction equation

HRID 2213140 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]2[C:9]([O:10][CH2:11][C:12]3([C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=4)[CH2:14][CH2:13]3)=[CH:8][CH:7]=[CH:6][N:5]2[C:21]=1[C:22](OCC)=[O:23].[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[CH3:1][C:2]1[N:3]=[C:4]2[C:9]([O:10][CH2:11][C:12]3([C:15]4[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=4)[CH2:14][CH2:13]3)=[CH:8][CH:7]=[CH:6][N:5]2[C:21]=1[CH2:22][OH:23]

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 70245761HCID 70245761, compound

Product 1

HCID 131725929HCID 131725929, compoundYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a cold (0°), stirred solution of ethyl 2-methyl-8-[(1-phenylcyclopropyl)methoxy]imidazo[1,2-α]pyridine-3-carboxylate (0.629 g, 1.83 mmol, see example 30) in anhydrous tetrahydrofuran (12 mL) under argon was added lithium aluminum hydride (0.104 g, 2.74 mmol). The reaction mixture was stirred for 1 h at 0° C., then quenched with water (25 mL) and extracted successively with ethyl acetate (75 mL) and dichloromethane (3×30 mL). The organic extracts were combined, dried over anhydrous sodium sulfate and concentrated in vacuo to yield 0.485 g (86% yield) of {2-methyl-8-[(1-phenylcyclopropyl)methoxy]imidazo[1,2-α]pyridin-3-yl}methanol free base as a pale yellow solid. A stirred solution of the free amine (0.479 g, 1.55 mmol) in anhydrous methanol (27 mL) was treated with ethereal hydrogen chloride to form the hydrochloride salt. After the solvent was removed in vacuo, the residue was triturated in anhydrous diethyl ether to yield a gummy solid. Recrystallization of this material from a mixture of diethyl ether and methanol yielded 0.509 g (95% yield) of the title compound as an off-white solid. 1H-NMR (300 MHz, CDCl3) δ 14.92 (s, 1H, +NH), 8.41 (s, 1H, Ar), 7.57 (m, 2H, Ar), 7.21 (m, 2H, Ar), 7.10 (m, 1H, Ar), 6.96 (m, 1H, Ar), 6.70 (m, 1H, Ar), 4.86 (s, 2H, HOCH2), 4.21 (s, 2H, CH2O), 2.59 (s, 3H, CH3), 1.06 (m, 4H, CH2CH2); 13C-NMR (75 MHz, CDCl3, APT) δ 144.21 (+), 142.21 (+), 132.30(+), 131.66(+), 129.87(−), 128.32(−), 126.81 (−), 123.23 (+), 119.12(−), 116.61 (−), 109.86 (−), 77.85 (+), 51.30 (+), 25.34 (+), 11.59 (+), 9.90 (−); LRMS-FAB m/z: MH+ 309 (100%); Anal. calcd for C19H20N2O2.HCl: C, 66.18; H, 6.14; N, 8.12%. found: C, 64.67; H, 6.36; N, 7.64%.

Workup

  1. customquenched with water (25 mL)
  2. extractionextracted successively with ethyl acetate (75 mL) and dichloromethane (3×30 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3beb168813904154bb6a83fd28a29b74
Source dataset
uspto-grants-2006_09
Patent number
US07105534B2

Reaction notes

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