Potassium Carbonate → 2-{(2S)-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-morpholin-4-yl}-1H-[4,4']bipyrimidinyl-6-one

HRID 2045908Notes

Reaction equation

HRID 2045908 reaction equation
Cl.[CH3:2][C:3]1[O:7][N:6]=[C:5]([C:8]2[CH:13]=[CH:12][C:11]([C@@H:14]3[O:19][CH2:18][CH2:17][NH:16][CH2:15]3)=[CH:10][CH:9]=2)[N:4]=1.Cl.[N:21]1([C:26](N)=[NH:27])C=CC=N1.C(N(CC)C(C)C)(C)C.C(O[C:41](=[O:51])[CH2:42][C:43](=O)[C:44]1[CH:49]=[CH:48][N:47]=[CH:46][N:45]=1)C.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C(O)C>[CH3:2][C:3]1[O:7][N:6]=[C:5]([C:8]2[CH:13]=[CH:12][C:11]([C@@H:14]3[O:19][CH2:18][CH2:17][N:16]([C:26]4[NH:27][C:41](=[O:51])[CH:42]=[C:43]([C:44]5[CH:49]=[CH:48][N:47]=[CH:46][N:45]=5)[N:21]=4)[CH2:15]3)=[CH:10][CH:9]=2)[N:4]=1

Participants

8

Reactant 5

HCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 2734672Pyrazole-1-carboxamidine monohydrochlorideHCID 11961458Ethyl 3-oxo-3-(pyrimidin-4-yl)propanoateHCID 66603801(2S)-2-(4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl)morpholine hydrochloride2×

Product 1

HCID 1359101862-{(2S)-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-morpholin-4-yl}-1H-[4,4']bipyrimidinyl-6-oneYield 33%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (2S)-2-(4-(5-methyl-1,2,4-oxadiazol-3-yl)phenyl)morpholine hydrochloride (intermediate 13, 4.00 g, 14.2 mmol) and 1H-pyrazole-1-carboxamidine hydrochloride (2.19 g, 14.9 mmol) in N,N-dimethylformamide (14 ml) was added. N,N-diisopropylethylamine (4.05 g, 31.3 mmol) at room temperature and the solution was stirred for 4 hours. The solution was decanted with ether, then 3-oxo-3-pyrimidin-4-yl-propionic acid ethyl ester (3.59 g, 18.5 mmol), potassium carbonate (4.92 g, 35.6 mmol) and ethanol (30 ml) were added to the resulting solution. After refluxed for 18 hours, the solution was concentrated under reduced pressure. The residue was washed with water and the hot mixture of ethanol and 1N hydrochloric acid (1/1, v/v), and dried under reduced pressure to afford 2-{(2S)-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-morpholin-4-yl}-1H-[4,4′]bipyrimidinyl-6-one (1.94 g, 33%).

Workup

  1. customThe solution was decanted with ether
  2. temperatureAfter refluxed for 18 hours
  3. concentrationthe solution was concentrated under reduced pressure
  4. washThe residue was washed with water
  5. additionthe hot mixture of ethanol and 1N hydrochloric acid (1/1
  6. customv/v), and dried under reduced pressure

Sources & evidence

ORD record
ord-698c32bb8c254a46a4c1c5a7996f0d20
Source dataset
uspto-grants-2013_11
Patent number
US08592417B2

Reaction notes

Loading…