Triethylamine → (R)-3-Oxo-3-(3-(2-(2-oxo-1,2-dihydropyridin-3-ylamino)pyrimidin-4-ylamino) piperidin-1-yl)propanenitrile

HRID 574004Notes

Reaction equation

HRID 574004 reaction equation
C(N(CC)CC)C.O=C1CCC(=O)N1[O:15][C:16](=O)[CH2:17][C:18]#[N:19].[NH:21]1[CH2:26][CH2:25][CH2:24][C@@H:23]([NH:27][C:28]2[CH:33]=[CH:32][N:31]=[C:30]([NH:34][C:35]3[C:36](=[O:41])[NH:37][CH:38]=[CH:39][CH:40]=3)[N:29]=2)[CH2:22]1>ClCCl>[O:15]=[C:16]([N:21]1[CH2:26][CH2:25][CH2:24][C@@H:23]([NH:27][C:28]2[CH:33]=[CH:32][N:31]=[C:30]([NH:34][C:35]3[C:36](=[O:41])[NH:37][CH:38]=[CH:39][CH:40]=3)[N:29]=2)[CH2:22]1)[CH2:17][C:18]#[N:19]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 534158962,5-Dioxopyrrolidin-1-yl 2-cyanoacetateHCID 71245038(R)-3-(4-(piperidin-3-ylamino)pyrimidin-2-ylamino)pyridin-2(1H)-one

Product 1

HCID 71245122(R)-3-Oxo-3-(3-(2-(2-oxo-1,2-dihydropyridin-3-ylamino)pyrimidin-4-ylamino) piperidin-1-yl)propanenitrileYield 13.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Triethylamine (33 μL, 0.24 mmol) and 3-[(2,5-dioxopyrrolidin-1-yl)oxy]-3-oxopropane nitrile (prepared as described in BE875054(A1), 51 mg, 0.28 mmol) were added to a solution of (R)-3-(4-(piperidin-3-ylamino)pyrimidin-2-ylamino)pyridin-2(1H)-one (Preparation 19c, 67 mg, 0.23 mmol) in dichloromethane (3 mL). The reaction mixture was stirred at ambient temperature for 24 hours and solvent was evaporated. Water was added and the mixture was extracted with dichloromethane. The organic layer was dried (MgSO4), evaporated under reduced pressure and the residue was purified by reverse phase chromatography (C-18 silica from Waters©, water/acetonitrile/methanol as eluents [0.1% v/v formic acid buffered] 0% to 100%) to give the title compound (11 mg, 12%) as a solid.

Workup

  1. customsolvent was evaporated
  2. additionWater was added
  3. extractionthe mixture was extracted with dichloromethane
  4. dry with materialThe organic layer was dried (MgSO4)
  5. customevaporated under reduced pressure
  6. customthe residue was purified by reverse phase chromatography (C-18 silica from Waters©, water/acetonitrile/methanol as eluents [0.1% v/v formic acid

Sources & evidence

ORD record
ord-b96213d4a58e4316b284eab2551e95e9
Source dataset
uspto-grants-2015_05
Patent number
US09034311B2

Reaction notes

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