Water → (S)-1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)-3-(4-(5-methyl-1H-tetrazol-1-yl)phenoxy)pyrrolidin-2-one

HRID 407952Notes

Reaction equation

HRID 407952 reaction equation
Cl.[CH3:2][C:3]1[N:7]([C:8]2[CH:26]=[CH:25][C:11]([O:12][C@H:13]3[CH2:17][CH2:16][N:15]([CH:18]4[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]4)[C:14]3=[O:24])=[CH:10][CH:9]=2)[N:6]=[N:5][N:4]=1.CCN(C(C)C)C(C)C.Cl[C:37]1[N:42]=[CH:41][C:40]([CH2:43][CH3:44])=[CH:39][N:38]=1.O>CN(C=O)C.CCOC(C)=O>[CH2:43]([C:40]1[CH:39]=[N:38][C:37]([N:21]2[CH2:20][CH2:19][CH:18]([N:15]3[CH2:16][CH2:17][C@H:13]([O:12][C:11]4[CH:10]=[CH:9][C:8]([N:7]5[C:3]([CH3:2])=[N:4][N:5]=[N:6]5)=[CH:26][CH:25]=4)[C:14]3=[O:24])[CH2:23][CH2:22]2)=[N:42][CH:41]=1)[CH3:44]

Participants

7

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 35727632-Chloro-5-ethylpyrimidineHCID 67470530(S)-3-(4-(5-methyl-1H-tetrazol-1-yl)phenoxy)-1-(piperidin-4-yl)pyrrolidin-2-one hydrochloride salt

Product 1

HCID 67470566(S)-1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)-3-(4-(5-methyl-1H-tetrazol-1-yl)phenoxy)pyrrolidin-2-oneYield 17%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (S)-3-(4-(5-methyl-1H-tetrazol-1-yl)phenoxy)-1-(piperidin-4-yl)pyrrolidin-2-one hydrochloride salt (128 mg, 0.198 mmol) and DIEA (0.173 mL, 0.99 mmol) in DMF (3 mL) was added 2-chloro-5-ethylpyrimidine (85 mg, 0.532 mmol). The reaction was heated to 100° C. for 4 hours and then 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 a gradient of 1:1 hexanes/EtOAc to EtOAc to yield (S)-1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)-3-(4-(5-methyl-1H-tetrazol-1-yl)phenoxy)pyrrolidin-2-one (15 mg, 17%) as an off white solid. Mass spectrum (apci) m/z=449.2 (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 a gradient of 1:1 hexanes/EtOAc to EtOAc

Sources & evidence

ORD record
ord-55544d2663e0448d915b785d2c1eb289
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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