Diisobutylaluminum hydride → 1-(2,2-Dimethylpropyl)-5-[(1R,2R)-2-(hydroxymethyl)cyclopropyl]-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

HRID 629906Notes

Reaction equation

HRID 629906 reaction equation
[CH3:1][C:2]([CH3:24])([CH3:23])[CH2:3][N:4]1[C:12]2[C:7](=[N:8][C:9]([C@@H:13]3[CH2:15][C@H:14]3[C:16](OCC)=[O:17])=[CH:10][CH:11]=2)[N:6]([CH3:21])[C:5]1=[O:22].CC(C[AlH]CC(C)C)C>C1COCC1>[CH3:1][C:2]([CH3:24])([CH3:23])[CH2:3][N:4]1[C:12]2[C:7](=[N:8][C:9]([C@@H:13]3[CH2:15][C@H:14]3[CH2:16][OH:17])=[CH:10][CH:11]=2)[N:6]([CH3:21])[C:5]1=[O:22]

Participants

4

Reactant 2

HCID 14487Diisobutylaluminum hydrideHCID 117718204Ethyl (1R,2R)-2-[1-(2,2-dimethylpropyl)-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl]cyclopropanecarboxylate

Product 1

HCID 1177025611-(2,2-Dimethylpropyl)-5-[(1R,2R)-2-(hydroxymethyl)cyclopropyl]-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Ethyl (1R,2R)-2-[1-(2,2-dimethylpropyl)-3-methyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl]cyclopropanecarboxylate (31-3, 126 mg, 0.38 mmol, 1.0 equiv) was added to anhydrous THF (3.8 mL) and cooled to 0° C. DIBAL-H (1.9 mL, 1.90 mmol, 5.0 equiv, 1.0M in THF) was added dropwise and the resulting solution was stirred at 0° C. for 2 h. The reaction was then quenched by the addition of saturated Rochelle salts (20 mL), diluted with EtOAc (10 mL) and stirred at RT for 18 h. Following this duration, the layers were separated and the aqueous layer was extracted with ethyl acetate (3×10 mL). The combined organics were dried over Na2SO4, filtered and concentrated in vacuo to give a clear, yellow oil. Purification by reverse-phase HPLC (10-100% 0.1% TFA in 1-120:CH3CN) provided 31-4 as a colorless oil.

Workup

  1. customThe reaction was then quenched by the addition of saturated Rochelle salts (20 mL)
  2. additiondiluted with EtOAc (10 mL)
  3. stirringstirred at RT for 18 h
  4. customthe layers were separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (3×10 mL)
  6. dry with materialThe combined organics were dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a clear, yellow oil
  10. customPurification by reverse-phase HPLC (10-100% 0.1% TFA in 1-120:CH3CN)

Sources & evidence

ORD record
ord-8fcd9f7f1a1747129662d18e587c2983
Source dataset
uspto-grants-2016_04
Patent number
US09315518B2

Reaction notes

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