Acetic Acid → HCID 178503313, compound

HRID 931282Notes

Reaction equation

HRID 931282 reaction equation
Cl.Cl.[NH2:3][C:4]1[CH:5]=[CH:6][C:7]([N:11]2[CH2:16][CH2:15][CH2:14][C@@H:13]([C:17]([N:19]3[CH2:23][CH2:22][CH2:21][CH2:20]3)=[O:18])[CH2:12]2)=[N:8][C:9]=1[NH2:10].[CH3:24][S:25][C:26]1[CH:27]=[N:28][N:29]([C:31]2([C:34](=N)OCC)[CH2:33][CH2:32]2)[CH:30]=1.C(O)(=O)C.C(N(CC)CC)C>C(O)C>[CH3:24][S:25][C:26]1[CH:27]=[N:28][N:29]([C:31]2([C:34]3[NH:10][C:9]4=[N:8][C:7]([N:11]5[CH2:16][CH2:15][CH2:14][C@@H:13]([C:17]([N:19]6[CH2:23][CH2:22][CH2:21][CH2:20]6)=[O:18])[CH2:12]5)=[CH:6][CH:5]=[C:4]4[N:3]=3)[CH2:32][CH2:33]2)[CH:30]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8471TriethylamineHCID 89854051(R)-(1-(5,6-Diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochlorideHCID 117966333HCID 117966333, compound

Product 1

HCID 178503313HCID 178503313, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of (R)-(1-(5,6-diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride (189 mg, 0.653 mmol) and ethyl 1-(4-(methylthio)-1H-pyrazol-1-yl)cyclopropanecarbimidate (157 mg, 0.697 mmol) in ethanol (1.86 mL) was added acetic acid (0.372 mL) followed by triethylamine (0.545 mL, 3.91 mmol). The reaction mixture was heated to 110° C. for 2 h. The mixture was cooled to room temperature, the solvent was removed under reduced pressure and the residue was partitioned between a saturated aqueous solution of ammonium chloride (100 mL) and dichloromethane (200 mL). The aqueous layer was extracted with dichloromethane (100 mL) and 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) 452.2; HPLC retention time 2.11 min (Method A).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. customthe solvent was removed under reduced pressure
  3. customthe residue was partitioned between a saturated aqueous solution of ammonium chloride (100 mL) and dichloromethane (200 mL)
  4. extractionThe aqueous layer was extracted with dichloromethane (100 mL)
  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-f8048c40c482400698a62186839f971f
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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