Methanol → 2-[(2-Chloro-pyridin-4-ylmethyl)-amino]-nicotinic acid methyl ester

HRID 602425Notes

Reaction equation

HRID 602425 reaction equation
[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][CH:7]=[N:6][C:5]=1[NH:10][C:11]([C:13]1[CH:18]=[CH:17][N:16]=[C:15]([Cl:19])[CH:14]=1)=O.B.CSC.CO>C1COCC1>[CH3:1][O:2][C:3](=[O:20])[C:4]1[CH:9]=[CH:8][CH:7]=[N:6][C:5]=1[NH:10][CH2:11][C:13]1[CH:18]=[CH:17][N:16]=[C:15]([Cl:19])[CH:14]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 12423031(Dimethyl sulfide)trihydroboronHCID 586749492-[(2-Chloro-pyridine-4-carbonyl)-amino]-nicotinic acid methyl ester

Product 1

HCID 586749472-[(2-Chloro-pyridin-4-ylmethyl)-amino]-nicotinic acid methyl esterYield 19.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A stirred solution of 2-[(2-chloro-pyridine-4-carbonyl)-amino]-nicotinic acid methyl ester (4 g, 13.72 mmol) in dry THF (60 mL), under nitrogen, was treated with borane-dimethyl sulphide complex (2M solution in THF, 34 mL, 68.6 mmol). On completion of the reaction the mixture was carefully poured into MeOH and the resulting mixture heated at reflux for 30 minutes. The volatiles were removed in vacuo and the residue partitioned between dilute aqueous sodium hydrogencarbonate solution and dichloromethane. The aqueous layer was extracted with dichloromethane and the combined organic layers washed with brine, dried and concentrated in vacuo. Purification was achieved by chromatography on Isolute® flash silica gel (Separtis) to give 2-[(2-chloro-pyridin-4-ylmethylamino]-nicotinic acid methyl ester (0.76 g); 1H-NMR (300 MHz, d6-DMSO) 8.47 (1H, t), 8.30 (1H, d), 8.23 (1H, unresolved dd), 8.13 (1H, unresolved dd), 7.38 (1H, s), 7.30 (1H, d), 6.68 (1H, dd), 4.73 (2H, d), 3.85 (3H, s).

Workup

  1. customOn completion of the reaction the mixture
  2. temperaturethe resulting mixture heated
  3. temperatureat reflux for 30 minutes
  4. customThe volatiles were removed in vacuo
  5. customthe residue partitioned between dilute aqueous sodium hydrogencarbonate solution and dichloromethane
  6. extractionThe aqueous layer was extracted with dichloromethane
  7. washthe combined organic layers washed with brine
  8. customdried
  9. concentrationconcentrated in vacuo
  10. customPurification

Sources & evidence

ORD record
ord-9eb1f2aca118401f800236d574c17d6c
Source dataset
uspto-grants-2011_03
Patent number
US07906533B2

Reaction notes

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