Water → HCID 50996946, compound

HRID 1424389Notes

Reaction equation

HRID 1424389 reaction equation
[CH2:1]([C:3]1[N:8]([CH2:9][C:10](=[O:17])[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:7](=[O:18])[C:6]2[C:19]([N:36](CC)[C:37](=O)[C:38](F)(F)F)=[C:20]([C:23]([NH:25][CH:26]3[CH2:31][CH2:30][N:29]([C:32](=[O:35])[CH2:33][OH:34])[CH2:28][CH2:27]3)=[O:24])[N:21]([CH3:22])[C:5]=2[CH:4]=1)[CH3:2].C(=O)([O-])[O-].[K+].[K+].O>CO>[CH2:1]([C:3]1[N:8]([CH2:9][C:10](=[O:17])[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:7](=[O:18])[C:6]2[C:19]([NH:36][CH2:37][CH3:38])=[C:20]([C:23]([NH:25][CH:26]3[CH2:31][CH2:30][N:29]([C:32](=[O:35])[CH2:33][OH:34])[CH2:28][CH2:27]3)=[O:24])[N:21]([CH3:22])[C:5]=2[CH:4]=1)[CH3:2]

Participants

5

Reactant 3

HCID 962WaterHCID 11430Potassium CarbonateHCID 86669130HCID 86669130, compound

Product 1

HCID 50996946HCID 50996946, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of the compound of Reference Example 25 (50 mg, 0.10 mmol), 2-(4-aminopiperidin-1-yl)-2-oxoethanol hydrochloride (24 mg, 0.13 mmol), HOBt (21 mg, 0.16 mmol), WSCD (30 mg, 0.16 mmol) and triethylamine (21 mg, 0.21 mmol) in DMF (2 ml) was stirred at room temperature for 2 days. The reaction mixture was diluted with saturated aqueous sodium hydrogen carbonate, and extracted twice with ethyl acetate. The extracts were combined, washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by aminosilica gel column chromatography (eluate, ethyl acetate) to give 6-ethyl-3-[ethyl(trifluoroacetyl)amino]-N-[1-(hydroxyacetyl)piperidin-4-yl]-1-methyl-4-oxo-5-(2-oxo-2-phenylethyl)-4,5-dihydro-1H-pyrrolo[3,2-c]pyridine-2-carboxamide (40 mg, 65%) as a colorless amorphous solid. A mixture of the 6-ethyl-3-[ethyl(trifluoroacetyl)amino]-N-[1-(hydroxyacetyl)piperidin-4-yl]-1-methyl-4-oxo-5-(2-oxo-2-phenylethyl)-4,5-dihydro-1H-pyrrolo[3,2-c]pyridine-2-carboxamide (40 mg, 0.065 mmol) and potassium carbonate (18 mg, 0.13 mmol) in methanol (3 mL) was stirred at room temperature for 3 hr. Water (10 mL) was added to the reaction mixture, and the mixture was concentrated under reduced pressure. The residue was partitioned between ethyl acetate and saturated aqueous sodium hydrogen carbonate, and the organic layer was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate-hexane to give the title compound (22 mg, 65%) as beige crystals.

Workup

  1. concentrationthe mixture was concentrated under reduced pressure
  2. customThe residue was partitioned between ethyl acetate and saturated aqueous sodium hydrogen carbonate
  3. washthe organic layer was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was recrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-33cbd306a7414963b4cb312a65eec0d4
Source dataset
uspto-grants-2015_01
Patent number
US08927718B2

Reaction notes

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