Water → N-(2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)-N-[4-(4H-1,2,4-triazol-4-yl)phenyl]acetamide

HRID 1039070Notes

Reaction equation

HRID 1039070 reaction equation
CC1C=CC(S(O[CH2:12][CH2:13][C@@H:14]2[CH2:16][C@@H:15]2[CH:17]2[CH2:22][CH2:21][N:20]([C:23]3[N:28]=[CH:27][C:26]([Cl:29])=[CH:25][N:24]=3)[CH2:19][CH2:18]2)(=O)=O)=CC=1.[N:30]1[N:31]=[CH:32][N:33]([C:35]2[CH:40]=[CH:39][C:38]([NH:41][C:42](=[O:44])[CH3:43])=[CH:37][CH:36]=2)[CH:34]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[Cl:29][C:26]1[CH:27]=[N:28][C:23]([N:20]2[CH2:19][CH2:18][CH:17]([C@H:15]3[CH2:16][C@H:14]3[CH2:13][CH2:12][N:41]([C:38]3[CH:37]=[CH:36][C:35]([N:33]4[CH:34]=[N:30][N:31]=[CH:32]4)=[CH:40][CH:39]=3)[C:42](=[O:44])[CH3:43])[CH2:22][CH2:21]2)=[N:24][CH:25]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 4086562N-[4-(4H-1,2,4-triazol-4-yl)phenyl]acetamideHCID 866661412-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl 4-methylbenzenesulfonate

Product 1

HCID 67777386N-(2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)-N-[4-(4H-1,2,4-triazol-4-yl)phenyl]acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl 4-methylbenzenesulfonate (60 mg, 0.14 mmol) from Example 5 step 1 and N-[4-(4H-1,2,4-triazol-4-yl)phenyl]acetamide (30.6 mg, 0.15 mmol) were added in DMF (0.7 mL), then cesium carbonate (224 mg, 0.69 mmol) was added and the reaction was heated to 50° C. overnight. The reaction was cooled to room temperature, water (10 mL) was added and extracted with ethyl acetate (20 mL), second wash with brine (10 mL). The organic phase was dried by magnesium sulfate, filtered, concentrated and purified by column chromatography through a 25 gram Biotage SNAP KP-Sil™silica gel cartridge eluting with 50% acetone/hexanes to give the title compound as a white solid.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. extractionextracted with ethyl acetate (20 mL)
  3. washsecond wash with brine (10 mL)
  4. dry with materialThe organic phase was dried by magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by column chromatography through a 25 gram Biotage SNAP KP-Sil™silica gel cartridge
  8. washeluting with 50% acetone/hexanes

Sources & evidence

ORD record
ord-28617cb42ca64f29aee5226ad345ffe5
Source dataset
uspto-grants-2013_10
Patent number
US08552022B2

Reaction notes

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