Acetonitrile → (2S,5R)-5-ethynyl-1-(N-(4-methyl-1-(3-cyano-pyridin-2-yl)piperidin-4-yl)glycyl)pyrrolidine-2-carbonitrile

HRID 475357Notes

Reaction equation

HRID 475357 reaction equation
[NH2:1][C:2]1([CH3:16])[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11](C#N)=[CH:10][N:9]=2)[CH2:4][CH2:3]1.Cl[CH2:18][C:19]([N:21]1[C@@H:25]([C:26]#[CH:27])[CH2:24][CH2:23][C@H:22]1[C:28]#[N:29])=[O:20].[C:30](#[N:32])C>>[C:26]([C@@H:25]1[N:21]([C:19](=[O:20])[CH2:18][NH:1][C:2]2([CH3:16])[CH2:3][CH2:4][N:5]([C:8]3[C:13]([C:30]#[N:32])=[CH:12][CH:11]=[CH:10][N:9]=3)[CH2:6][CH2:7]2)[C@H:22]([C:28]#[N:29])[CH2:23][CH2:24]1)#[CH:27]

Participants

4

Reactant 3

HCID 6342AcetonitrileHCID 129691214-Amino-1-(5-cyano-2-pyridyl)-4-methylpiperidineHCID 16090854(2S,5R)-1-(2-chloroacetyl)-5-ethynylpyrrolidine-2-carbonitrile

Product 1

HCID 46851905(2S,5R)-5-ethynyl-1-(N-(4-methyl-1-(3-cyano-pyridin-2-yl)piperidin-4-yl)glycyl)pyrrolidine-2-carbonitrile

Procedure

A mixture of Example 30D (60 mg, 0.31 mmol) and (2S,5R)-1-(chloroacetyl)-5-ethynylpyrrolidine-2-carbonitrile (105 mg, 0.49 mmol, Example 8D) in acetonitrile (2 mL) was stirred at 23° C. for 72 hours. The reaction mixture was concentrated under reduced pressure, and the crude residue was purified by chromatography (silica gel, eluting with 96% dichloromethane/4% methanol/0.1% ammonium hydroxide) to provide the titled compound as a white foam. MS (CI) m/z 377 (M+1)+; 1H NMR (300 MHz, CDCl3) δ ppm 8.38 (s, 1H), 7.58 (dd, 1H), 6.59 (d, 1H), 4.74 (t, 1H), 4.63-4.57 (m, 1H), 3.78-3.68 (m, 6H), 2.53 (s, 1H), 2.43-2.34 (m, 2H), 1.69-1.50 (m, 4H), 1.19 (s, 3H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe crude residue was purified by chromatography (silica gel, eluting with 96% dichloromethane/4% methanol/0.1% ammonium hydroxide)

Sources & evidence

ORD record
ord-0fd7aedf04d640fc8093e1172f05822b
Source dataset
uspto-grants-2014_01
Patent number
US08637546B2

Reaction notes

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