Sodium Hydroxide → [9-Methoxy-1-(2-methoxy-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]methanol

HRID 1629019Notes

Reaction equation

HRID 1629019 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH3:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([C:32](OC)=[O:33])=[C:13]2[C:17]=1[N:16]=[C:15]1[N:18]([C:22]3[C:23]([CH3:31])=[N:24][C:25]([O:29][CH3:30])=[N:26][C:27]=3[CH3:28])[CH2:19][CH2:20][CH2:21][N:14]21.[OH-].[Na+].S([O-])([O-])(=O)=O.[Mg+2]>O1CCCC1.O>[CH3:7][O:8][C:9]1[C:17]2[N:16]=[C:15]3[N:18]([C:22]4[C:23]([CH3:31])=[N:24][C:25]([O:29][CH3:30])=[N:26][C:27]=4[CH3:28])[CH2:19][CH2:20][CH2:21][N:14]3[C:13]=2[C:12]([CH2:32][OH:33])=[CH:11][CH:10]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 24083Sulfuric acid magnesium salt (1:1)HCID 21226445Aluminium lithium hydrideHCID 57785995Methyl 9-methoxy-1-(2-methoxy-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylate

Product 1

HCID 57786030[9-Methoxy-1-(2-methoxy-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]methanolYield 71.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of lithium aluminum hydride (0.14 g, 3.69 mmol) in tetrahydrofuran (10 mL) was added dropwise a solution of methyl 9-methoxy-1-(2-methoxy-4,6-dimethylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylate (720 mg, 1.81 mmol) in tetrahydrofuran (30 mL) at 0° C. After stirring at 0° C. for 1 hr, water (0.14 mL), 15% aqueous sodium hydroxide (0.14 mL) and water (0.42 mL) were successively added dropwise to the reaction mixture at 0° C. The mixture was stirred at room temperature for 4 hr and anhydrous magnesium sulfate was added to the mixture. The solid was removed by filtration. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel eluting with a 5-25% methanol/ethyl acetate gradient mixture to give the title compound as a colorless solid (478 mg, 1.29 mmol, 71%).

Workup

  1. stirringThe mixture was stirred at room temperature for 4 hr
  2. customThe solid was removed by filtration
  3. concentrationThe filtrate was concentrated in vacuo
  4. customthe residue was purified by flash column chromatography on silica gel eluting with a 5-25% methanol/ethyl acetate gradient mixture

Sources & evidence

ORD record
ord-c7d0affc4e954c3b8c94a5ca959067f3
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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