Trifluoroacetic acid → Methyl 6-amino-5-chloro-2-(3-fluorophenyl)nicotinate

HRID 717828Notes

Reaction equation

HRID 717828 reaction equation
[Cl:1][C:2]1[C:3]([NH:19]CC2C=CC(OC)=C(OC)C=2)=[N:4][C:5]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].FC(F)(F)C(O)=O>>[NH2:19][C:3]1[C:2]([Cl:1])=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[C:5]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)[N:4]=1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66993070Methyl 5-chloro-6-[(3,4-dimethoxybenzyl)amino]-2-(3-fluorophenyl)nicotinate

Product 1

HCID 58515985Methyl 6-amino-5-chloro-2-(3-fluorophenyl)nicotinateYield 76.7%

Procedure

A solution of methyl 5-chloro-6-[(3,4-dimethoxybenzyl)amino]-2-(3-fluorophenyl)nicotinate (0.11 g, 0.26 mmol) in trifluoroacetic acid (4 mL, 50 mmol) was heated at 60° C. for 22 hours. The reaction mixture was concentrated, diluted with methanol, and filtered. The filtrate was concentrated and purified via RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) to give the desired product (56 mg, 75%). LCMS calculated for C13H11ClFN2O2 (M+H)+: m/z=281.0. found: 280.8.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. additiondiluted with methanol
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated
  5. custompurified via RP-HPLC (XBridge C18 column
  6. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-9af2435025ab4278b8c6cf63fbba3e0b
Source dataset
uspto-grants-2015_11
Patent number
US09193721B2

Reaction notes

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