Diisopropylethylamine → Methyl 4-[(6-chloro-3-methyl-pyridine-2-carbonyl)amino]-3,5-dimethyl-benzoate

HRID 239916

Reaction equation

HRID 239916 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([C:8]([O-:10])=O)[CH:5]=[CH:4][CH:3]=1.[K+].O=[C:13]1N([ClH]P([ClH]N2CCOC2=O)=O)CCO1.[NH2:28][C:29]1[C:38]([CH3:39])=[CH:37][C:32]([C:33]([O:35][CH3:36])=[O:34])=[CH:31][C:30]=1[CH3:40].C(N(C(C)C)CC)(C)C>CN(C)C=O.O>[Cl:1][C:2]1[N:7]=[C:6]([C:8]([NH:28][C:29]2[C:30]([CH3:40])=[CH:31][C:32]([C:33]([O:35][CH3:36])=[O:34])=[CH:37][C:38]=2[CH3:39])=[O:10])[C:5]([CH3:13])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 11030398Benzoic acid, 4-amino-3,5-dimethyl-, methyl esterHCID 86707310Potassium 6-chloropyridine-2-carboxylate

Product 1

HCID 86707309Methyl 4-[(6-chloro-3-methyl-pyridine-2-carbonyl)amino]-3,5-dimethyl-benzoateYield 86.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a suspension of potassium 6-chloropyridine-2-carboxylate (52 g, 265.8 mmoles) in dimethylformamide (676 mL) is added bis(2-oxo-3-oxazolidinyl)phosphonic chloride (115 g, 451.8 mmoles). The mixture is stirred at ambient temperature for 30 minutes. Methyl 4-amino-3,5-dimethyl-benzoate (42.9 g, 239.2 mmoles, see preparation 12) and diisopropylethylamine (115.9 mL, 664.5 mmoles) are added. The reaction is stirred at ambient temperature for 16 hours. The mixture is then poured into water (2000 mL) and is stirred for 30 minutes. The resulting solid is filtered and dried under reduced pressure at 45° C. The dry material is triturated with hexane (1400 mL) over 2 hours. The solid is filtered and dried under vacuum to give the title compound (69 g, 78%) as a white solid. Mass spectrum (m/z): 333.05 (M+1). 1H NMR (300 MHz, DMSO): 10.16 (s, 1H), 7.89 (d, J=8.2 Hz, 1H), 7.73 (s, 2H), 7.63 (d, J=8.2 Hz, 1H), 3.85 (s, 3H), 2.49 (s, 3H), 2.28 (s, 6H).

Workup

  1. stirringThe reaction is stirred at ambient temperature for 16 hours
  2. stirringis stirred for 30 minutes
  3. filtrationThe resulting solid is filtered
  4. customdried under reduced pressure at 45° C
  5. customThe dry material is triturated with hexane (1400 mL) over 2 hours
  6. filtrationThe solid is filtered
  7. customdried under vacuum

Sources & evidence

ORD record
ord-f6bb69db1dff4b349f23b9bbba4ba0fb
Source dataset
uspto-grants-2014_02
Patent number
US08642768B2

Linked notes

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