Triethylamine → HCID 19736673, compound

HRID 326282

Reaction equation

HRID 326282 reaction equation
[NH2:1][C:2]1[CH:11]=[C:10]([Cl:12])[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].Cl.[N:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1CC(O)=O.C(N(CC)CC)C.O=C1N(P(Cl)(N2CCOC2=O)=O)[CH2:35][CH2:34][O:33]1.N1C=CC=CC=1CC(O)=O>ClCCCl>[Cl:12][C:10]1[CH:9]=[CH:8][C:3]([C:4]([O:6][CH3:7])=[O:5])=[C:2]([NH:1][C:34](=[O:33])[CH2:35][C:18]2[CH:19]=[N:14][CH:15]=[CH:16][CH:17]=2)[CH:11]=1

Participants

7

Reactant 5

HCID 8471Triethylamine2×HCID 80001Methyl 4-chloroanthranilateHCID 853172-Pyridineacetic acid, hydrochloride (1:1)HCID 853182-Pyridineacetic acidHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chloride

Product 1

HCID 19736673HCID 19736673, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of methyl 2-amino-4-chlorobenzoate (2 g, 10.8 mmol) in 1,2-dichlorethane (60 ml) was added 2-pyridylacetic acid hydrochloride (1.9 g, 10.8 mmol), triethylamine (3.2 ml, 22.7 mmol) and bis (2-oxo-3-oxazolidinyl)phosphinic chloride and the reaction refluxed for 8 h. More 2-pyridylacetic acid (1.9 g, 10.8 mmol) and triethylamine (3.2 ml, 22.7 mmol) were added and refluxing continued for a further 16 h. The solvent was evaporated and the residue partitioned between saturated aqueous sodium bicarbonate solution (50 ml) and dichloromethane (50 ml). The organic phase was dried (MgSO4) and evaporated. The residue was purified by flash chromatography on silica (eluting with 50% ethyl acetate/60°-90° petrol) to afford methyl 4-chloro-2-(3-pyridyl)acetamidobenzoate as a green solid (2.5 g), m.p. 85°-87° C. To a solution of the foregoing amide (1 g, 3.3 mmol) in tetrahydrofuran (40 mml) was added a solution of potassium hexamethyldisilazide in toluene (0.5M, 16.6 ml, 8.3 mmol) and the reaction stirred for 2 h. Methanol (15 ml) was added and the solvent evaporated. The residue was partitioned between aqueous sodium hydroxide (1M, 40 ml) and diethyl ether (40 ml), and the aqueous layer acidified with hydrochloric acid (5M). The resultant precipitate was collected and recrystallised from dimethylformamide/water to afford the title compound as a yellow-green solid; m.p.>330° C. (from DMF/H2O) (Found: C, 61.48; H, 3.20; N, 10.20; C14H9ClN2O2 requires C, 61.66; H, 3.33; N, 10.27%); δH (DMSO-d6) 7.15 (1H, dd, J=8.5 Hz and 1.9 Hz, 5-H), 7.26 (1H, s, 8-H), 7.42 (1H, t, J=6.1 Hz, 5'-H), 8.02 (1H, d, J=8.5 Hz, 5-H), 8.16 (1H, t, J=7.3 Hz, 4'-H), 8.78 (1H, d, J=8.6 Hz, 6'-H), 9.38 (1H, d, J=8.8 Hz, 3'-H), 11.20 (1H, s, NH); m/z 272 (M+).

Workup

  1. temperaturethe reaction refluxed for 8 h
  2. temperaturerefluxing
  3. customThe solvent was evaporated
  4. customthe residue partitioned between saturated aqueous sodium bicarbonate solution (50 ml) and dichloromethane (50 ml)
  5. dry with materialThe organic phase was dried (MgSO4)
  6. customevaporated
  7. customThe residue was purified by flash chromatography on silica (eluting with 50% ethyl acetate/60°-90° petrol)

Sources & evidence

ORD record
ord-c2682c8eec7843e69178a774e2b5f3fc
Source dataset
uspto-grants-1993_12
Patent number
US05268378

Linked notes

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