Acetic Acid → HCID 178468904, compound

HRID 931212Notes

Reaction equation

HRID 931212 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(O)(=O)C.C(N(CC)CC)C.Cl.C(O[C:39](=N)[C:40]1[CH:41]=[C:42]([CH:48]=[C:49]([CH2:51][CH3:52])[N:50]=1)[C:43]([O:45][CH2:46][CH3:47])=[O:44])C>C(O)C>[CH2:51]([C:49]1[CH:48]=[C:42]([CH:41]=[C:40]([C:39]2[NH:10][C:9]3=[N:8][C:7]([N:11]4[CH2:16][CH2:15][CH2:14][C@@H:13]([C:17]([N:19]5[CH2:23][CH2:22][CH2:21][CH2:20]5)=[O:18])[CH2:12]4)=[CH:6][CH:5]=[C:4]3[N:3]=2)[N:50]=1)[C:43]([O:45][CH2:46][CH3:47])=[O:44])[CH3:52]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8471TriethylamineHCID 89852906HCID 89852906, compoundHCID 89854051(R)-(1-(5,6-Diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride

Product 1

HCID 178468904HCID 178468904, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
110 °C

Procedure

To a solution (R)-(1-(5,6-diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride (116 mg, 0.595 mmol) in anhydrous ethanol (5.0 mL) was added acetic acid (0.293 mL, 5.12 mmol) followed by triethylamine (0.179 mL, 1.28 mmol). Ethyl 2-(ethoxy(imino)methyl)-6-ethylisonicotinate hydrochloride (80 mg, 0.32 mmol) was added and the reaction mixture was heated to 110° C. for 30 min. The reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure. The residue was partitioned between a saturated aqueous solution of ammonium chloride (50 mL) and ethyl acetate (50 mL). The pH of the aqueous layer was adjusted to 3 using an aqueous solution of hydrochloric acid (1N). The aqueous layer was extracted with ethyl acetate (50 mL×2). The combined organic layers were washed with brine, 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) 477.2; HPLC retention time 2.7 min (Method A).

Workup

  1. temperatureThe reaction 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 (50 mL) and ethyl acetate (50 mL)
  4. extractionThe aqueous layer was extracted with ethyl acetate (50 mL×2)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude material was purified via HPLC

Sources & evidence

ORD record
ord-0901e796486641f7b949371eaa899057
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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