Acetic Acid → HCID 178521015, compound

HRID 931277Notes

Reaction equation

HRID 931277 reaction equation
[CH:1]1([C:4]2[CH:5]=[N:6][CH:7]=[C:8]([CH:14]=2)[C:9](=[NH:13])OCC)[CH2:3][CH2:2]1.C(O)(=O)C.C(N(CC)CC)C.Cl.Cl.[NH2:28][C:29]1[CH:30]=[CH:31][C:32]([N:36]2[CH2:41][CH2:40][CH2:39][C@@H:38]([C:42]([N:44]3[CH2:48][CH2:47][CH2:46][CH2:45]3)=[O:43])[CH2:37]2)=[N:33][C:34]=1N>C(O)C>[CH:1]1([C:4]2[CH:14]=[C:8]([C:9]3[NH:13][C:34]4=[N:33][C:32]([N:36]5[CH2:41][CH2:40][CH2:39][C@@H:38]([C:42]([N:44]6[CH2:48][CH2:47][CH2:46][CH2:45]6)=[O:43])[CH2:37]5)=[CH:31][CH:30]=[C:29]4[N:28]=3)[CH:7]=[N:6][CH:5]=2)[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8471TriethylamineHCID 89853752Ethyl 5-cyclopropylnicotinimidateHCID 89854051(R)-(1-(5,6-Diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride

Product 1

HCID 178521015HCID 178521015, compoundYield 5.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To a solution of ethyl 5-cyclopropylnicotinimidate (0.2 g, 1.04 mmol) in ethanol was added acetic acid (0.1 mL), triethylamine (0.1 mL) and a solution of (R)-(1-(5,6-diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride salt (0.4 g, 1.1 mmol) in ethanol. The reaction mixture was heated at reflux for 24 h. The solvent was removed under reduced pressure and to the resulting residue was added a saturated aqueous solution of ammonium chloride. The mixture was extracted with ethyl acetate. The organic layer was concentrated under reduced pressure. The crude material was purified via preparative TLC to afford the title compound (0.025 g). 1H NMR (400 MHz, DMSO-d6) δ 0.85 (br s, 2H), 1.07 (d, 2H), 1.47-1.74 (m, 4H), 1.74-1.96 (m, 5H), 1.98-2.10 (m, 1H), 2.61 (br s, 2H), 2.92 (d, 2H), 3.41-3.59 (m, 2H), 4.33 (d, 1H), 4.39 (d, 1H), 6.86 (d, 1H), 7.81 (d, 1H), 8.00 (br s, 1H), 8.47 (br s, 1H), 9.05 (br s, 1H), 13.07 (br s, 1H). MS (ES+) (M+H) 417.36; LCMS retention time 3.03 min (Method S).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 24 h
  3. customThe solvent was removed under reduced pressure and to the resulting residue
  4. additionwas added a saturated aqueous solution of ammonium chloride
  5. extractionThe mixture was extracted with ethyl acetate
  6. concentrationThe organic layer was concentrated under reduced pressure
  7. customThe crude material was purified via preparative TLC

Sources & evidence

ORD record
ord-18c3e61935e5430d967f3ea2d2868b9d
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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