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

HRID 2199559Notes

Reaction equation

HRID 2199559 reaction equation
C[N:2](/[CH:4]=[C:5](/[C:8](=O)[CH3:9])\[C:6]#N)C.C(O)C.CC(O)C.[CH3:18][N:19]1[CH2:24][CH2:23][CH:22]([CH2:25][CH2:26][CH2:27][NH:28][C:29]([NH2:31])=[NH:30])[CH2:21][CH2:20]1.C(=O)([O-])[O-].[K+].[K+]>>[CH3:9][C:8]1[C:5]([C:4]#[N:2])=[CH:6][N:31]=[C:29]([NH:28][CH2:27][CH2:26][CH2:25][CH:22]2[CH2:21][CH2:20][N:19]([CH3:18])[CH2:24][CH2:23]2)[N:30]=1

Participants

5

Reactant 4

HCID 11430Potassium CarbonateHCID 22179027Isopropanol ethanol3×HCID 299417973-(Dimethylamino)-2-acetylacrylonitrile2×HCID 178480300HCID 178480300, compound

Product 1

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

Conditions

Temperature
72.5 °C

Procedure

In a 100 L glass-lined reactor, a solution of (E)-2-[(dimethylamino)methylene]-3-oxobutanenitrile in ethanol/2-propanol (4.48 kg, 32.43 mol in 8.81 kg of ethanol/2-propanol) was added at 20-25° C. to a stirring solution of N-[3-(N-methyl-4-piperidinyl)-1-propyl]guanidine in ethanol/2-propanol (5.41 kg, 27.28 mol in 28.35 kg of ethanol/2-propanol). The resultant mixture was heated for 1.5 h at reflux, followed by an additional charge of (E)-2-[(dimethylamino)methylene]-3-oxobutanenitrile in ethanol/2-propanol (2.02 kg, 14.57 mol in 3.96 kg of ethanol/2-propanol). The resultant mixture was stirred and cooled to 70-75° C. and then potassium carbonate (7.50 kg, 54.26 mol) was added. The resultant mixture was heated to reflux until the reaction was deemed complete by HPLC. When the reaction was deemed complete, about 35-40 L of solvent was removed via atmospheric distillation. The heating was discontinued and purified water (80.00 kg) was added to the resultant suspension, which was then cooled to 20-25° C. and stirred for about 1 h. The resultant suspension was then further cooled to 0-5° C. and aged for 30 min. The solid was filtered, washed with purified water (40.00 kg) and dried at 75-80° C. under vacuum to yield the title compound.

Workup

  1. temperatureat reflux
  2. temperatureto reflux until the reaction
  3. customabout 35-40 L of solvent was removed via atmospheric distillation
  4. custompurified water (80.00 kg)
  5. additionwas added to the resultant suspension, which
  6. temperaturewas then cooled to 20-25° C.
  7. temperatureThe resultant suspension was then further cooled to 0-5° C. and aged for 30 min
  8. filtrationThe solid was filtered
  9. washwashed with purified water (40.00 kg)
  10. customdried at 75-80° C. under vacuum

Sources & evidence

ORD record
ord-943e223825424d8789d6ad051d679cd6
Source dataset
uspto-grants-2016_06
Patent number
US09359327B2

Reaction notes

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