Water → (S)-1-(1-(5-ethylpyrimidin-2-yl)piperidine-4-yl)-3-(6-(methylsulfonyl)pyridine-3-yloxy)pyrrolidin-2-one

HRID 407949Notes

Reaction equation

HRID 407949 reaction equation
Cl.[CH3:2][S:3]([C:6]1[N:11]=[CH:10][C:9]([O:12][C@H:13]2[CH2:17][CH2:16][N:15]([CH:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)[C:14]2=[O:24])=[CH:8][CH:7]=1)(=[O:5])=[O:4].CCN(C(C)C)C(C)C.Cl[C:35]1[N:40]=[CH:39][C:38]([CH2:41][CH3:42])=[CH:37][N:36]=1.O>CN(C=O)C.CCOC(C)=O>[CH2:41]([C:38]1[CH:37]=[N:36][C:35]([N:21]2[CH2:22][CH2:23][CH:18]([N:15]3[CH2:16][CH2:17][C@H:13]([O:12][C:9]4[CH:10]=[N:11][C:6]([S:3]([CH3:2])(=[O:4])=[O:5])=[CH:7][CH:8]=4)[C:14]3=[O:24])[CH2:19][CH2:20]2)=[N:40][CH:39]=1)[CH3:42]

Participants

7

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 35727632-Chloro-5-ethylpyrimidineHCID 67469724(S)-3-(6-(methylsulfonyl)pyridin-3-yloxy)-1-(piperidin-4-yl)pyrrolidin-2-one hydrochloride salt

Product 1

HCID 67469827(S)-1-(1-(5-ethylpyrimidin-2-yl)piperidine-4-yl)-3-(6-(methylsulfonyl)pyridine-3-yloxy)pyrrolidin-2-oneYield 30.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (S)-3-(6-(methylsulfonyl)pyridin-3-yloxy)-1-(piperidin-4-yl)pyrrolidin-2-one hydrochloride salt (100 mg, 0.26 mmol) and DIEA (0.324 mL, 1.86 mmol) in DMF (3 mL) was added 2-chloro-5-ethylpyrimidine (76 mg, 0.532 mmol). The reaction was heated to 100° C. for 4 hours at which point the reaction was poured into water (10 mL) and EtOAc (10 mL). The organic layer was separated and the aqueous layer extracted with EtOAc (2×5 mL). The combined organic layers were dried with MgSO4 and concentrated in vacuo. The resulting material was purified by silica gel chromatography eluting with 1:1 hexanes/EtOAc to EtOAc to yield (S)-1-(1-(5-ethylpyrimidin-2-yl)piperidine-4-yl)-3-(6-(methylsulfonyl)pyridine-3-yloxy)pyrrolidin-2-one (35 mg, 30%) as an off white solid. Mass spectrum (apci) m/z=452.2 (M+H).

Workup

  1. customThe organic layer was separated
  2. extractionthe aqueous layer extracted with EtOAc (2×5 mL)
  3. dry with materialThe combined organic layers were dried with MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe resulting material was purified by silica gel chromatography
  6. washeluting with 1:1 hexanes/EtOAc to EtOAc

Sources & evidence

ORD record
ord-ffd6a5512cf043b1be6304e888720f04
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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