Lithium Hydroxide → 6-(7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)nicotinic acid

HRID 627325Notes

Reaction equation

HRID 627325 reaction equation
[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[CH:25]=[CH:24][C:19]([C:20]([O:22]C)=[O:21])=[CH:18][N:17]=4)[N:13]=[CH:14][C:9]=3[CH:8]=[C:7]2[C:26](=[O:30])[N:27]([CH3:29])[CH3:28])[CH2:5][CH2:4][CH2:3][CH2:2]1.[Li+].[OH-]>C1COCC1>[CH:1]1([N:6]2[C:10]3[N:11]=[C:12]([NH:15][C:16]4[CH:25]=[CH:24][C:19]([C:20]([OH:22])=[O:21])=[CH:18][N:17]=4)[N:13]=[CH:14][C:9]=3[CH:8]=[C:7]2[C:26](=[O:30])[N:27]([CH3:28])[CH3:29])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 67240111methyl 6-(7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)nicotinate

Product 1

HCID 583154726-(7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)nicotinic acidYield 80.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

To a suspension of methyl 6-(7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)nicotinate (2.0 g, 4.9 mmol) in THF (6 mL) was added 1M LiOH (aq) (6 mL, 1.2 equiv) and the slurry stirred at 45° C. for 12 hours (the slurry became clear). After cooling to room temperature, the THF was evaporated and the reaction mixture was treated with 1 N HCl until pH=1-2. The resulting precipitate was filtered and the filtrate extracted with 20% Isopropanol/CH2Cl2 (3×100 mL), the combined organic layers dried, filtered, and concentrated to a tan solid. The tan solid was triturated in acetone giving 6-(7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino) nicotinic acid as the desired product as a tan solid (1.56 g, 73% yield) which was used without further purification.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe THF was evaporated
  3. additionthe reaction mixture was treated with 1 N HCl until pH=1-2
  4. filtrationThe resulting precipitate was filtered
  5. extractionthe filtrate extracted with 20% Isopropanol/CH2Cl2 (3×100 mL)
  6. customthe combined organic layers dried
  7. filtrationfiltered
  8. concentrationconcentrated to a tan solid
  9. customThe tan solid was triturated in acetone

Sources & evidence

ORD record
ord-e7ef19c0148f46a99ff6482c75358549
Source dataset
uspto-grants-2016_04
Patent number
US09309252B2

Reaction notes

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