Tetrahydrofuran → HCID 178467897, compound

HRID 2065810Notes

Reaction equation

HRID 2065810 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[NH:13][C:12]([C:14]2([C:17](OC)=[O:18])[CH2:16][CH2:15]2)=[N:11][C:10]=1[C:21]1[N:26]=[C:25]2[O:27][C:28]([NH:30][C@@H:31]([CH3:36])[CH2:32][O:33][CH2:34][CH3:35])=[N:29][C:24]2=[CH:23][CH:22]=1.C1COCC1.[BH4-].[Li+]>C(OCC)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[NH:13][C:12]([C:14]2([CH2:17][OH:18])[CH2:15][CH2:16]2)=[N:11][C:10]=1[C:21]1[N:26]=[C:25]2[O:27][C:28]([NH:30][C@@H:31]([CH3:36])[CH2:32][O:33][CH2:34][CH3:35])=[N:29][C:24]2=[CH:23][CH:22]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 4148881Lithium borohydrideHCID 178467898HCID 178467898, compound

Product 1

HCID 178467897HCID 178467897, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

Methyl 1-[5-(2,4-difluorophenyl)-4-[2-[[(1S)-2-ethoxy-1-methyl-ethyl]amino]oxazolo[5,4-b]pyridin-5-yl]-1H-imidazol-2-yl]cyclopropanecarboxylate (0.9 g, 1.99 mmol) is dissolved in dry diethyl ether (20 mL) and dry THF (7 mL) under a nitrogen atmosphere and cooled to 0° C. Lithium borohydride (87 mg, 3.99 mmol) is added portionwise and the mixture stirred at 0° C. for 1 h. The remaining reactants are quenched by adding 1 N HCl until pH=1 to the mixture at RT dropwise for 30 min. The mixture is washed with ethyl acetate, the aqueous layer basified (until pH=8) with NaOH, and extracted with dichloromethane. The combined organic layers are dried over MgSO4, filtered, and concentrated under reduced pressure. The residue is purified by normal phase chromatography (120 g silica-gel cartridge) using a gradient of hexane-ethanol to afford the title compound (0.56 g, 60%). LC-ES/MS m/z 470.2 (M+1); [α]D22−18.00°, (c=0.50, MeOH); [α]D22−18.0°, (c=0.50, CHCl3).

Workup

  1. customThe remaining reactants are quenched
  2. additionby adding 1 N HCl until pH=1 to the mixture at RT dropwise for 30 min
  3. washThe mixture is washed with ethyl acetate
  4. extractionextracted with dichloromethane
  5. dry with materialThe combined organic layers are dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue is purified by normal phase chromatography (120 g silica-gel cartridge)

Sources & evidence

ORD record
ord-0d43c56ab74a4e0a93715d2f7ea3cdae
Source dataset
uspto-grants-2012_10
Patent number
US08288548B2

Reaction notes

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