Diisopropylethylamine → tert-butyl 6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-4-(5-fluoropicolinoyl)-1H-benzo[d]imidazole-1-carboxylate

HRID 1773686Notes

Reaction equation

HRID 1773686 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[C:9]([CH:26]([C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][N:29]=3)[OH:27])[C:10]3[N:14]=[C:13]([O:15][CH2:16][CH3:17])[N:12]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C:11]=3[CH:25]=2)=[C:5]([CH3:35])[O:4][N:3]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.C(N(CC)C(C)C)(C)C.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O>ClCCl.CN(C)C1C=CN=CC=1>[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[C:9]([C:26](=[O:27])[C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][N:29]=3)[C:10]3[N:14]=[C:13]([O:15][CH2:16][CH3:17])[N:12]([C:18]([O:20][C:21]([CH3:23])([CH3:24])[CH3:22])=[O:19])[C:11]=3[CH:25]=2)=[C:5]([CH3:35])[O:4][N:3]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 90495Di-tert-butyl dicarbonateHCID 159087TriacetoxyperiodinaneHCID 117600940tert-butyl 6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-4-((5-fluoropyridin-2-yl)(hydroxy)methyl)-1H-benzo[d]imidazole-1-carboxylate

Product 1

HCID 117601919tert-butyl 6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-4-(5-fluoropicolinoyl)-1H-benzo[d]imidazole-1-carboxylate

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To tert-butyl 6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-4-((5-fluoropyridin-2-yl)(hydroxy)methyl)-1H-benzo[d]imidazole-1-carboxylate (57 mg, 0.12 mmol) in dichloromethane (6 mL) was added Dess-Martin periodinane (154.1 mg, 0.34 mmol). After 15 minutes, the reaction was quenched with saturated Na2S2O3(aq) (10 mL) and extracted with dichloromethane (3×10 mL). The combined organics were washed with water (30 mL) and brine (30 mL), and dried over Na2SO4. To the crude solution was added N,N-diisopropylethylamine (0.05 mL, 0.26 mmol), 4-(dimethylamino)pyridine (6.8 mg, 0.05 mmol), and di-tert-butyl dicarbonate (120.9 mg). After 90 minutes, the reaction mixture was washed with water (2×30 mL), dried over Na2SO4, and concentrated in vacuo. Purification by flash chromatography (0-50% ethyl acetate/hexane) afforded tert-butyl 6-(3,5-dimethylisoxazol-4-yl)-2-ethoxy-4-(5-fluoropicolinoyl)-1H-benzo[d]imidazole-1-carboxylate as an amber residue.

Workup

  1. customthe reaction was quenched with saturated Na2S2O3(aq) (10 mL)
  2. extractionextracted with dichloromethane (3×10 mL)
  3. washThe combined organics were washed with water (30 mL) and brine (30 mL)
  4. dry with materialdried over Na2SO4
  5. waitAfter 90 minutes
  6. washthe reaction mixture was washed with water (2×30 mL)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customPurification by flash chromatography (0-50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-aa3998bcc12243929ebb7eedeb58dfa5
Source dataset
uspto-grants-2016_02
Patent number
US09255089B2

Reaction notes

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