Oxalyl chloride → N-{3-[2-amino-6-(2-{[tert-butyl(dimethyl)silyl]oxy}phenyl)-3-cyano-4-pyridinyl]phenyl}-3-(1-piperidinyl)propanamide

HRID 2218251Notes

Reaction equation

HRID 2218251 reaction equation
[N:1]1([CH2:7][CH2:8][C:9]([OH:11])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.[NH2:18][C:19]1[N:26]=[C:25]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35])[CH:24]=[C:23]([C:41]2[CH:46]=[CH:45][CH:44]=[C:43]([NH2:47])[CH:42]=2)[C:20]=1[C:21]#[N:22]>ClCCl.C(#N)C>[NH2:18][C:19]1[C:20]([C:21]#[N:22])=[C:23]([C:41]2[CH:42]=[C:43]([NH:47][C:9](=[O:11])[CH2:8][CH2:7][N:1]3[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]3)[CH:44]=[CH:45][CH:46]=2)[CH:24]=[C:25]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=2[O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:35])[CH3:36])[N:26]=1

Participants

6

Reactant 3

HCID 65578Oxalyl chlorideHCID 1177821-Piperidinepropanoic acidHCID 597696742-Amino-4-(3-aminophenyl)-6-(2-{[tert-butyl(dimethyl)silyl]oxy}phenyl)nicotinonitrile2×

Product 1

HCID 69144979N-{3-[2-amino-6-(2-{[tert-butyl(dimethyl)silyl]oxy}phenyl)-3-cyano-4-pyridinyl]phenyl}-3-(1-piperidinyl)propanamideYield 45%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a cold (0° C.) solution of 3-(1-piperidinyl)-propanoic acid (0.676 g, 3.601 mmol) in dichloromethane was added oxalyl chloride (0.471 mL, 5.401 mmol) and stirred at room temperature for 12 hrs. The mixture was concentrated under reduced pressure. The residue was added to the solution of 2-amino-4-(3-aminophenyl)-6-(2-{[tert-butyl(dimethyl)silyl]oxy}-phenyl)nicotinonitrile (starting compound 2, 1.500 g, 3.601 mmol) in acetonitrile (3 mL), and the resulting mixture was stirred at 0° C. for 1 hr. The reaction mixture was extracted with ethyl acetate and water. The separated organic phase was washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. Purification was carried out by silica gel column chromatography (chloroform/methanol=10/1) to give N-{3-[2-amino-6-(2-{[tert-butyl(dimethyl)silyl]oxy}phenyl)-3-cyano-4-pyridinyl]phenyl}-3-(1-piperidinyl)propanamide as a white solid (0.860 g, yield 45%).

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. stirringthe resulting mixture was stirred at 0° C. for 1 hr
  3. extractionThe reaction mixture was extracted with ethyl acetate and water
  4. washThe separated organic phase was washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification

Sources & evidence

ORD record
ord-4233f018a4d5494cbc227a97cf94c8b3
Source dataset
uspto-grants-2008_08
Patent number
US07410986B2

Reaction notes

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