Acetic Acid → HCID 178423611, compound

HRID 931210Notes

Reaction equation

HRID 931210 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].C(N(CC)CC)C.Cl.[C:32]1([CH3:46])[CH:37]=[CH:36][C:35]([C:38]2([C:41](=N)OCC)[CH2:40][CH2:39]2)=[CH:34][CH:33]=1.C(O)(=O)C>C(O)C>[N:19]1([C:17]([C@@H:13]2[CH2:14][CH2:15][CH2:16][N:11]([C:7]3[N:8]=[C:9]4[NH:10][C:41]([C:38]5([C:35]6[CH:34]=[CH:33][C:32]([CH3:46])=[CH:37][CH:36]=6)[CH2:39][CH2:40]5)=[N:3][C:4]4=[CH:5][CH:6]=3)[CH2:12]2)=[O:18])[CH2:23][CH2:22][CH2:21][CH2:20]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8471TriethylamineHCID 89853579HCID 89853579, compoundHCID 89854051(R)-(1-(5,6-Diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride

Product 1

HCID 178423611HCID 178423611, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
130 °C

Procedure

To a suspension of (R)-(1-(5,6-diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride (220 mg, 0.60 mmol) in ethanol (2 mL) was added triethylamine (250 μL, 1.8 mmol), a solution of ethyl 1-(p-tolyl)cyclopropanecarbimidate hydrochloride (140 mg, 0.58 mmol) in ethanol (1 mL), and acetic acid (0.5 mL, 8.70 mmol). The reaction mixture was heated in a microwave for 45 min at 130° C. The solvent was removed under reduced pressure. Ethyl acetate (10 mL) was added to the residue and the solution was washed with aqueous sodium hydroxide (1N, 5 mL). The aqueous layer was extracted with ethyl acetate (10 mL×3). The combined organics were washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified via HPLC to afford the title compound. MS (ESI+) (M+H) 430.2; HPLC retention time 2.51 min (Method A).

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionEthyl acetate (10 mL) was added to the residue
  3. washthe solution was washed with aqueous sodium hydroxide (1N, 5 mL)
  4. extractionThe aqueous layer was extracted with ethyl acetate (10 mL×3)
  5. washThe combined organics were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified via HPLC

Sources & evidence

ORD record
ord-1b78d060d4334e90b838ed27223f0e05
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

Loading…