Acetic Acid → HCID 178493806, compound

HRID 931284Notes

Reaction equation

HRID 931284 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[N:5][N:6]([C:8]2([C:11](=[NH:15])OCC)[CH2:10][CH2:9]2)[CH:7]=1.Cl.Cl.[NH2:18][C:19]1[CH:20]=[CH:21][C:22]([N:26]2[CH2:31][CH2:30][CH2:29][C@@H:28]([C:32]([N:34]3[CH2:38][CH2:37][CH2:36][CH2:35]3)=[O:33])[CH2:27]2)=[N:23][C:24]=1N.C(O)(=O)C.C(N(CC)CC)C.[Cl-].[NH4+]>C(O)C>[CH3:1][O:2][C:3]1[CH:4]=[N:5][N:6]([C:8]2([C:11]3[NH:15][C:24]4=[N:23][C:22]([N:26]5[CH2:31][CH2:30][CH2:29][C@@H:28]([C:32]([N:34]6[CH2:38][CH2:37][CH2:36][CH2:35]6)=[O:33])[CH2:27]5)=[CH:21][CH:20]=[C:19]4[N:18]=3)[CH2:9][CH2:10]2)[CH:7]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 89854051(R)-(1-(5,6-Diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochlorideHCID 117966276Ethyl 1-(4-methoxy-1H-pyrazol-1-yl)cyclopropanecarbimidate

Product 1

HCID 178493806HCID 178493806, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of crude ethyl 1-(4-methoxy-1H-pyrazol-1-yl)cyclopropanecarbimidate (79.5 mg, 0.380 mmol) in ethanol (1.5 mL) was added (R)-(1-(5,6-diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride (151 mg, 0.417 mmol) followed by glacial acetic acid (0.435 mL, 7.59 mmol). The mixture was degassed with nitrogen, and then triethylamine (0.318 mL, 2.28 mmol) was added. The reaction mixture was heated at 100° C. for 20 min and then at 85° C. for 18 h. The mixture was poured into a saturated aqueous solution of ammonium chloride (40 mL) and extracted with dichloromethane (50 mL×3). The combined organics were washed with a saturated aqueous solution of sodium bicarbonate. The aqueous layer was extracted with dichloromethane (40 mL×2). The combined organics were dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified via HPLC to afford the title compound. MS (ESI+) (M+H) 436.2; HPLC retention time 1.85 min (Method A).

Workup

  1. customThe mixture was degassed with nitrogen
  2. extractionextracted with dichloromethane (50 mL×3)
  3. washThe combined organics were washed with a saturated aqueous solution of sodium bicarbonate
  4. extractionThe aqueous layer was extracted with dichloromethane (40 mL×2)
  5. dry with materialThe combined organics were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was purified via HPLC

Sources & evidence

ORD record
ord-b896a86a6cca482ea9f90a24f57b327c
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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