Triethylamine → N2,N2-dimethyl-N1-(4-((2S)-4-(3-methyl-4-oxo-3,4-dihydro-6-(3-fluoropyridin-4-yl)pyrimidin-2-yl)-morpholin-2-yl)phenyl)glycinamide

HRID 1091406Notes

Reaction equation

HRID 1091406 reaction equation
[CH3:1][N:2]([CH3:19])[CH2:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([C@@H:13]2[O:18][CH2:17][CH2:16][NH:15][CH2:14]2)=[CH:9][CH:8]=1)=[O:5].Cl[C:21]1[N:26]([CH3:27])[C:25](=[O:28])[CH:24]=[C:23]([C:29]2[CH:34]=[CH:33][N:32]=[CH:31][C:30]=2[F:35])[N:22]=1.C(N(CC)CC)C>O1CCCC1>[CH3:1][N:2]([CH3:19])[CH2:3][C:4]([NH:6][C:7]1[CH:8]=[CH:9][C:10]([C@@H:13]2[O:18][CH2:17][CH2:16][N:15]([C:21]3[N:26]([CH3:27])[C:25](=[O:28])[CH:24]=[C:23]([C:29]4[CH:34]=[CH:33][N:32]=[CH:31][C:30]=4[F:35])[N:22]=3)[CH2:14]2)=[CH:11][CH:12]=1)=[O:5]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 595768122-Chloro-3-methyl-6-(3-fluoropyridin-4-yl)-3H-pyrimidin-4-oneHCID 66594891N2,N2-dimethyl-N1-(4-((2S)-morpholin-2-yl)phenyl)glycinamide

Product 1

HCID 11698414N2,N2-dimethyl-N1-(4-((2S)-4-(3-methyl-4-oxo-3,4-dihydro-6-(3-fluoropyridin-4-yl)pyrimidin-2-yl)-morpholin-2-yl)phenyl)glycinamideYield 50%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
95 °C

Procedure

A solution of N2,N2-dimethyl-N1-(4-((2S)-morpholin-2-yl)phenyl)glycinamide obtained in Reference Example 13 (0.21 g, 0.8 mmol), 2-chloro-6-(3-fluoropyridin-4-yl)-3-methyl-3H-pyrimidin-4-one (0.15 g, 0.64 mmol), and triethylamine (0.40 g, 4 mmol) in tetrahydrofuran (10 ml) was stirred at 95° C. for one hour. The solvent was removed in vacuo and the residue was partitioned between water and dichloromethane. The organic layer was dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform/methanol=10/1) to afford N2,N2-dimethyl-N1-(4-((2S)-4-(3-methyl-4-oxo-3,4-dihydro-6-(3-fluoropyridin-4-yl)pyrimidin-2-yl)-morpholin-2-yl)phenyl)glycinamide (0.15 g, 50%) as colorless crystals.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was partitioned between water and dichloromethane
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. customthe solvent was removed under reduced pressure
  5. customThe resulting residue was purified by silica gel column chromatography (chloroform/methanol=10/1)

Sources & evidence

ORD record
ord-200c33a5d01a4ecfbd810e1b16d52efc
Source dataset
uspto-grants-2012_03
Patent number
US08129377B2

Reaction notes

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