Acetone → 7-(7-(2-Hydroxypropan-2-yl)-6-oxo-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid

HRID 517883Notes

Reaction equation

HRID 517883 reaction equation
[O:1]=[C:2]1[N:25]([CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][C:32]([OH:34])=[O:33])[C:6]2=[N:7][C:8]([C:18]3[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=3)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=3)[N:10]=[C:5]2[CH2:4][CH2:3]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:45][C:46]([CH3:48])=[O:47]>C1COCC1>[OH:47][C:46]([CH:3]1[C:2](=[O:1])[N:25]([CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][C:32]([OH:34])=[O:33])[C:6]2=[N:7][C:8]([C:18]3[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=3)=[C:9]([C:11]3[CH:12]=[CH:13][C:14]([CH3:17])=[CH:15][CH:16]=3)[N:10]=[C:5]2[CH2:4]1)([CH3:48])[CH3:45]

Participants

5

Reactant 3

HCID 180AcetoneHCID 2733832Lithium HexamethyldisilazideHCID 666657007-(6-oxo-2,3-dip-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid

Product 1

HCID 716574237-(7-(2-Hydroxypropan-2-yl)-6-oxo-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A cooled (−78° C.) solution of 7-(6-oxo-2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid (step 2) (100 mg, 0.219 mmol) in THF (5 ml) under a nitrogen atmosphere was treated dropwise with lithium bis trimethylsilylamide (1M in THF, 0.546 ml, 0.546 mmol). The mixture was stirred at −78° C. for 10 minutes and treated with acetone (0.100 ml, 0.546 mmol) in THF (2 ml) maintaining the internal temperature below −65° C. Once addition was complete, the reaction was quenched with sat. NH4Cl (aq). The organic portion was separated and the aqueous was extracted with ethyl acetate (×2). The combined organic extracts were concentrated under reduced pressure and the crude product was purified by chromatography on silica eluting with 0-10% MeOH in DCM to afford the titled compound;

Workup

  1. temperaturemaintaining the internal temperature below −65° C
  2. additionOnce addition
  3. customthe reaction was quenched with sat. NH4Cl (aq)
  4. customThe organic portion was separated
  5. extractionthe aqueous was extracted with ethyl acetate (×2)
  6. concentrationThe combined organic extracts were concentrated under reduced pressure
  7. customthe crude product was purified by chromatography on silica eluting with 0-10% MeOH in DCM

Sources & evidence

ORD record
ord-32c5ca4194b240aa8a4e0303c92d6c79
Source dataset
uspto-grants-2015_08
Patent number
US09115129B2

Reaction notes

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