Methylamine → 2-Chloro-6-[4-(methylamino)piperidin-1-yl]isonicotinonitrile

HRID 2233856Notes

Reaction equation

HRID 2233856 reaction equation
CN.[Cl:3][C:4]1[CH:5]=[C:6]([CH:9]=[C:10]([N:12]2[CH2:17][CH2:16][C:15](=O)[CH2:14][CH2:13]2)[N:11]=1)[C:7]#[N:8].ClC1C=C(C=C(N2CCC(O)CC2)N=1)[C:23]#[N:24].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1>[Cl:3][C:4]1[CH:5]=[C:6]([CH:9]=[C:10]([N:12]2[CH2:17][CH2:16][CH:15]([NH:24][CH3:23])[CH2:14][CH2:13]2)[N:11]=1)[C:7]#[N:8]

Participants

6

Reactant 4

HCID 6329MethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 717484322-Chloro-6-(4-oxopiperidin-1-yl)isonicotinonitrileHCID 830734032-Chloro-6-(4-hydroxypiperidin-1-yl)isonicotinonitrile

Product 1

HCID 860383832-Chloro-6-[4-(methylamino)piperidin-1-yl]isonicotinonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methylamine (2.65 ml, 5.3 mmol) was added to a solution of 2-chloro-6-(4-oxopiperidin-1-yl)isonicotinonitrile (Intermediate 26; 500 mg, 2.12 mmol) in anhydrous THF (4 ml). The mixture was stirred for 30 minutes and sodium triacetoxyborohydride (674 mg, 3.18 mmol) was added. The mixture was stirred at room temperature for 18 h, then concentrated in vacuo, diluted with EtOAc and washed with 1 N NaOH, water and brine. The organic phase was dried over Na2SO4 then concentrated in vacuo to give a brown oil which was dried under vacuum to yield the title compound (507 mg).

Workup

  1. stirringThe mixture was stirred at room temperature for 18 h
  2. concentrationconcentrated in vacuo
  3. additiondiluted with EtOAc
  4. washwashed with 1 N NaOH, water and brine
  5. dry with materialThe organic phase was dried over Na2SO4
  6. concentrationthen concentrated in vacuo
  7. customto give a brown oil which
  8. customwas dried under vacuum

Sources & evidence

ORD record
ord-1e6b205f0853498eacce823b37a68b42
Source dataset
uspto-grants-2010_05
Patent number
US07709503B2

Reaction notes

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