Nicotinic Acid → [4-(3-Pyridylcarbonylamino)-2-phenylbenzoyl]methionine methyl ester

HRID 2121175Notes

Reaction equation

HRID 2121175 reaction equation
[C:1]([OH:9])(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[CH3:16][O:17][C:18](=[O:40])[C@H:19]([CH2:36][CH2:37][S:38][CH3:39])[NH:20][C:21](=[O:35])[C:22]1[CH:27]=[CH:26][C:25]([NH2:28])=[CH:24][C:23]=1[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.C([O-])(O)=O.[Na+]>ClCCl.CN(C=O)C>[CH3:16][O:17][C:18](=[O:40])[C@H:19]([CH2:36][CH2:37][S:38][CH3:39])[NH:20][C:21](=[O:35])[C:22]1[CH:27]=[CH:26][C:25]([NH:28][C:1]([C:2]2[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=2)=[O:9])=[CH:24][C:23]=1[C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

7

Reactant 4

HCID 938Nicotinic AcidHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 18666758N-(4-Amino-2-phenylbenzoyl)methionine methyl ester

Product 1

HCID 10837807[4-(3-Pyridylcarbonylamino)-2-phenylbenzoyl]methionine methyl esterYield 96%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
25 °C

Procedure

Nicotinic acid (345 mg, 2.8 mmol) was suspended in 10 mL of dichloromethane and oxalyl chloride (2.8 mL of a 2.0 M soln in methylene chloride) was added by syringe followed by one drop of DMF. The reaction mixture was stirred at 25° C. for 2 hours and then was evaporated and azeotroped with toluene. The resulting acid chloride was then dissolved in dichloromethane and a solution of (4-amino-2-phenylbenzoyl)methionine methyl ester (669 mg, 1.87 mmol), prepared as in Example 192B, in 5 mL of dichloromethane was added followed by 4 mL of saturated aqeuous NaHCO3 and the reaction was stirred at 25° C. for 3 hours. The layers were separated and the organic layer was dried over Na2SO4, filtered and evaporated to give 830 mg (96%) of [4-(3-pyridylcarbonylamino)-2-phenylbenzoyl]methionine methyl ester as an oil. 1H NMR (300 mHz, CDCl3) δ 9.2 (d, 1H), 8.76 (d, 1H), 8.42 (bs, 1H), 8.2 (dt, 1H), 7.72-7.65 (m, 2H), 7.6 (dd, 1H), 7.45-7.35 (m, 5H), 6.02 (bd, 1H), 4.65 (dq, 1H), 3.68 (s, 3H), 2.20 (t, 2H), 2.01 (s, 3H), 1.98-1.88 (m, 1H), 1.80-1.78 (m, 1H). CIMS 464 (M+H)+.

Workup

  1. customwas evaporated
  2. customazeotroped with toluene
  3. dissolutionThe resulting acid chloride was then dissolved in dichloromethane
  4. stirringthe reaction was stirred at 25° C. for 3 hours
  5. customThe layers were separated
  6. dry with materialthe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-66d6eeff585341f69f31e31c88fc32d4
Source dataset
uspto-grants-2004_02
Patent number
US06693123B2

Reaction notes

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