Acetic Acid → HCID 178481783, compound

HRID 931211Notes

Reaction equation

HRID 931211 reaction equation
[CH3:1][N:2]1[C:6]([CH2:7][C:8]#[N:9])=[CH:5][CH:4]=[N:3]1.[C:10](Cl)(=O)[CH3:11].Cl.Cl.N[C:17]1[CH:18]=[CH:19][C:20]([N:24]2[CH2:29][CH2:28][CH2:27][C@@H:26]([C:30]([N:32]3[CH2:36][CH2:35][CH2:34][CH2:33]3)=[O:31])[CH2:25]2)=[N:21][C:22]=1[NH2:23].C(N(CC)CC)C.C(O)(=O)C>C(O)C>[CH3:1][N:2]1[C:6]([C:7]2([C:8]3[NH:23][C:22]4=[N:21][C:20]([N:24]5[CH2:29][CH2:28][CH2:27][C@@H:26]([C:30]([N:32]6[CH2:36][CH2:35][CH2:34][CH2:33]6)=[O:31])[CH2:25]5)=[CH:19][CH:18]=[C:17]4[N:9]=3)[CH2:11][CH2:10]2)=[CH:5][CH:4]=[N:3]1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 252483742-(1-methyl-1H-pyrazol-5-yl)acetonitrileHCID 89854051(R)-(1-(5,6-Diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride

Product 1

HCID 178481783HCID 178481783, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To a solution of 2-(1-methyl-1H-pyrazol-5-yl)acetonitrile (14.5 mg, 0.10 mmol) in ethanol (150 μL, 2.6 mmol) was added acetyl chloride (110 μL, 1.5 mmol). The reaction mixture was stirred at room temperature for 16 h. The solvent was removed under a stream of nitrogen. Ethanol (0.5 mL) was added to the residue followed by a solution of (R)-(1-(5,6-diaminopyridin-2-yl)piperidin-3-yl)(pyrrolidin-1-yl)methanone dihydrochloride (36 mg, 0.01 mmol) and triethylamine (70 μL, 0.50 mmol) in ethanol (1 mL). Acetic acid (100 μL, 1.75 mmol) was added and the reaction mixture was heated in the microwave for 45 min at 130° C. The solvent was removed under a stream of nitrogen. Ethyl acetate (10 mL) was added to the residue. The solution was washed with aqueous sodium hydroxide (1N, 3 mL), washed with water (3 mL), washed with brine (3 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude material was purified via HPLC to afford the title compound. MS (ESI+) (M+H) 420.3; HPLC retention time 1.88 min (Method B).

Workup

  1. customThe solvent was removed under a stream of nitrogen
  2. additionEthanol (0.5 mL) was added to the residue
  3. temperaturethe reaction mixture was heated in the microwave for 45 min at 130° C
  4. customThe solvent was removed under a stream of nitrogen
  5. additionEthyl acetate (10 mL) was added to the residue
  6. washThe solution was washed with aqueous sodium hydroxide (1N, 3 mL)
  7. washwashed with water (3 mL)
  8. washwashed with brine (3 mL)
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe crude material was purified via HPLC

Sources & evidence

ORD record
ord-061c00ae9b70407cb3b1423857ec3dce
Source dataset
uspto-grants-2016_03
Patent number
US09296745B2

Reaction notes

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