Water → 9-Chloro-1-[6-methoxy-2-(trifluoromethyl)pyridin-3-yl]-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carbaldehyde

HRID 1399364Notes

Reaction equation

HRID 1399364 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[C:16]([C:23]([F:26])([F:25])[F:24])=[N:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=4)[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH2:27][OH:28])=[CH:4][CH:3]=1.CC1(C)N([O])C(C)(C)CCC1.[N+]([O-])([O-])=O.[Na+].O>C(O)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:27]=[O:28])=[C:6]2[C:10]=1[N:9]=[C:8]1[N:11]([C:15]3[C:16]([C:23]([F:25])([F:24])[F:26])=[N:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=3)[CH2:12][CH2:13][CH2:14][N:7]21

Participants

6

Reactant 4

HCID 962WaterHCID 24268Sodium NitrateHCID 2724126TempoHCID 57786319{9-Chloro-1-[6-methoxy-2-(trifluoromethyl)pyridin-3-yl]-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl}methanol

Product 1

HCID 441565019-Chloro-1-[6-methoxy-2-(trifluoromethyl)pyridin-3-yl]-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole-6-carbaldehydeYield 68%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of {9-chloro-1-[6-methoxy-2-(trifluoromethyl)pyridin-3-yl]-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl}methanol (500 mg, 1.21 mmol), 2,2,6,6-tetramethylpiperidine 1-oxyl (18.9 mg, 0.12 mmol) and sodium nitrate (33.4 mg, 0.484 mmol) in acetic acid (10 mL) was stirred at room temperature and ambient pressure for 64 hr. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with aqueous sodium hydrogen carbonate and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with a 20-80% ethyl acetate/n-hexane gradient mixture to give the title compound (336.3 mg, 0.82 mmol, 68%) as a pale yellow solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with aqueous sodium hydrogen carbonate and brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography on silica gel eluting with a 20-80% ethyl acetate/n-hexane gradient mixture

Sources & evidence

ORD record
ord-15e572e190854714ae20f965120bdda2
Source dataset
uspto-grants-2014_12
Patent number
US08901141B2

Reaction notes

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