Water → HCID 67470507, compound

HRID 407943Notes

Reaction equation

HRID 407943 reaction equation
Cl.Cl.[N:3]1([C:8]2[N:13]=[CH:12][C:11]([O:14][CH:15]3[CH2:19][CH2:18][N:17]([CH:20]4[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]4)[C:16]3=[O:26])=[CH:10][CH:9]=2)[CH:7]=[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>[N:3]1([C:8]2[N:13]=[CH:12][C:11]([O:14][CH:15]3[CH2:19][CH2:18][N:17]([CH:20]4[CH2:21][CH2:22][N:23]([C:37]5[N:42]=[CH:41][C:40]([CH2:43][CH3:44])=[CH:39][N:38]=5)[CH2:24][CH2:25]4)[C:16]3=[O:26])=[CH:10][CH:9]=2)[CH:7]=[N:6][N:5]=[N:4]1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 35727632-Chloro-5-ethylpyrimidineHCID 67470611HCID 67470611, compound

Product 1

HCID 67470507HCID 67470507, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 3-(6-(1H-tetrazol-1-yl)pyridin-3-yloxy)-1-(piperidin-4-yl)pyrrolidin-2-one bishydrochloride salt (101 mg, 0.25 mmol) and DIEA (0.30 mL, 1.75 mmol) in DMF (3 mL) was added 2-chloro-5-ethylpyrimidine (71 mg, 0.50 mmol). The reaction was heated at 100° C. for 6 hours. The reaction was cooled to ambient temperature and diluted by the addition of water (5 mL). The aqueous layer was extracted with EtOAc (3×10 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The material was purified by silica gel chromatography eluting with a gradient of 2:1 hexanes/EtOAc up to 100% EtOAc to yield 3-(6-(1H-tetrazol-1-yl)pyridin-3-yloxy)-1-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yl)pyrrolidin-2-one (52 mg, 48%) as an off white solid. Mass spectrum (apci) m/z=383.2 (M-N3CH+3H).

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. extractionThe aqueous layer was extracted with EtOAc (3×10 mL)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe material was purified by silica gel chromatography
  8. washeluting with a gradient of 2:1 hexanes/EtOAc up to 100% EtOAc

Sources & evidence

ORD record
ord-baeb5e9d206c498e897e7de6646bd455
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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