Water → 4-Methyl-2-[3-(1-methyl-piperidin-4-yl)-propylamino]-pyrimidine-5-carbonitrile

HRID 2199556Notes

Reaction equation

HRID 2199556 reaction equation
CCOC(C)=O.O.[C:8]([C:10]1[C:11]([CH3:30])=[N:12][C:13]([N:16]([CH2:20][CH2:21][CH2:22][CH:23]2[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]2)C(=O)C)=[N:14][CH:15]=1)#[N:9]>Cl>[CH3:30][C:11]1[C:10]([C:8]#[N:9])=[CH:15][N:14]=[C:13]([NH:16][CH2:20][CH2:21][CH2:22][CH:23]2[CH2:28][CH2:27][N:26]([CH3:29])[CH2:25][CH2:24]2)[N:12]=1

Participants

5

Reactant 3

HCID 962WaterHCID 8857Ethyl AcetateHCID 68527494N-(5-cyano-4-methyl-pyrimidin-2-yl)-N-[3-(1-methyl-piperidin-4-yl)-propyl]-acetamide

Product 1

HCID 445457774-Methyl-2-[3-(1-methyl-piperidin-4-yl)-propylamino]-pyrimidine-5-carbonitrile

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

The resultant mixture was treated at 20-25° C. with a dilute HCl solution (37% HCl (4.80 g) diluted with water (15.00 g)), followed by EtOAc (9.02 g) and water (10.00 g). The resultant mixture was settled and the top organic layer was removed. The acidic aqueous layer was stirred at room temperature for 1 h to yield a mixture (which contained the hydrolysis product, N-(5-cyano-4-methyl-pyrimidin-2-yl)-N-[3-(1-methyl-piperidin-4-yl)-propyl]-acetamide). The aqueous layer was extracted one time with EtOAc (9.02 g). 2-Methyl-THF (8.60 g) was added and the pH of the biphasic mixture was adjusted to about pH=12 by addition of 6N NaOH (9.69 g). The aqueous layer was removed and the 2-Me-THF layer was diluted with 2-MeT-HF (8.60 g) and dried with MgSO4 (1.0 g). The pH of the dried 2-MeTHF solution was adjusted to about pH=1 by dropwise addition of 5-6N HCl/IPA, whereupon the HCl salt of the title compound precipitated. The solid was filtered, dissolved in EtOH (3.95 g) and the pH was adjusted to about pH=12 using 6N NaOH (4.85 g). The solid which precipitated during the addition was filtered, washed with water (10.00 g) and dried in a vacuum oven at 60-70° C. for 5 h to yield the title compound as a solid.

Workup

  1. customthe top organic layer was removed
  2. customto yield a mixture (which
  3. extractionThe aqueous layer was extracted one time with EtOAc (9.02 g)
  4. addition2-Methyl-THF (8.60 g) was added
  5. additionthe pH of the biphasic mixture was adjusted to about pH=12 by addition of 6N NaOH (9.69 g)
  6. customThe aqueous layer was removed
  7. additionthe 2-Me-THF layer was diluted with 2-MeT-HF (8.60 g)
  8. dry with materialdried with MgSO4 (1.0 g)
  9. additionThe pH of the dried 2-MeTHF solution was adjusted to about pH=1 by dropwise addition of 5-6N HCl/IPA, whereupon the HCl salt of the title compound
  10. customprecipitated
  11. filtrationThe solid was filtered
  12. dissolutiondissolved in EtOH (3.95 g)
  13. customThe solid which precipitated during the addition
  14. filtrationwas filtered
  15. washwashed with water (10.00 g)
  16. customdried in a vacuum oven at 60-70° C. for 5 h

Sources & evidence

ORD record
ord-a3039eee6f6d405f962aef95e7683c58
Source dataset
uspto-grants-2016_06
Patent number
US09359327B2

Reaction notes

Loading…