Triacetoxyperiodinane → 9-Chloro-1-(4,6-dimethoxy-2-methylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carbaldehyde

HRID 1628859Notes

Reaction equation

HRID 1628859 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:26](OC)=[O:27])=[C:6]2[C:10]=1[N:9]=[C:8]1[N:11]([C:15]3[C:16]([O:24][CH3:25])=[N:17][C:18]([CH3:23])=[N:19][C:20]=3[O:21][CH3:22])[CH2:12][CH2:13][CH2:14][N:7]21.[BH4-].[Li+].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>O1CCCC1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:26]=[O:27])=[C:6]2[C:10]=1[N:9]=[C:8]1[N:11]([C:15]3[C:16]([O:24][CH3:25])=[N:17][C:18]([CH3:23])=[N:19][C:20]=3[O:21][CH3:22])[CH2:12][CH2:13][CH2:14][N:7]21

Participants

6

Reactant 3

HCID 159087TriacetoxyperiodinaneHCID 4148881Lithium borohydrideHCID 57785929Methyl 9-chloro-1-(4,6-dimethoxy-2-methylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylate

Product 1

HCID 577863749-Chloro-1-(4,6-dimethoxy-2-methylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carbaldehydeYield 75.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of methyl 9-chloro-1-(4,6-dimethoxy-2-methylpyrimidin-5-yl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carboxylate (627 mg, 1.50 mmol) in tetrahydrofuran (15 mL) was added lithium borohydride (131 mg, 6.00 mmol) at room temperature. After being stirred for 15 h at 0° C., the reaction mixture was quenched with aqueous ammonium chloride, extracted with ethyl acetate, and concentrated in vacuo. The resulting solid was washed with ethyl acetate and dissolved in dimethyl sulfoxide (15 mL). To the solution was added Dess-Martin reagent (1.27 g, 3.00 mmol) at room temperature, and the mixture was stirred for 15 h. The reaction mixture was diluted with ethyl acetate, quenched with aqueous sodium hydrogen carbonate, washed with water and brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 20-80% ethyl acetate/hexane gradient mixture to give the title compound as a pale yellow solid (439 mg, 75%).

Workup

  1. customthe reaction mixture was quenched with aqueous ammonium chloride
  2. extractionextracted with ethyl acetate
  3. concentrationconcentrated in vacuo
  4. washThe resulting solid was washed with ethyl acetate
  5. dissolutiondissolved in dimethyl sulfoxide (15 mL)
  6. stirringthe mixture was stirred for 15 h
  7. customquenched with aqueous sodium hydrogen carbonate
  8. washwashed with water and brine
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by flash column chromatography on silica gel eluting with a 20-80% ethyl acetate/hexane gradient mixture

Sources & evidence

ORD record
ord-79554342083a4a8b9e2afcd8251f4ab8
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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