3-Pyridinecarbonyl chloride, hydrochloride (1:1) → [4-(3-Pyridylcarbonylamino)-2-(2-methylphenyl)benzoyl]methionine Methyl Ester

HRID 2121229Notes

Reaction equation

HRID 2121229 reaction equation
[CH3:1][O:2][C:3](=[O:26])[C@H:4]([CH2:22][CH2:23][S:24][CH3:25])[NH:5][C:6](=[O:21])[C:7]1[CH:12]=[CH:11][C:10]([NH2:13])=[CH:9][C:8]=1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[CH3:20].Cl.[C:28](Cl)(=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[N:31][CH:30]=1.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:26])[C@H:4]([CH2:22][CH2:23][S:24][CH3:25])[NH:5][C:6](=[O:21])[C:7]1[CH:12]=[CH:11][C:10]([NH:13][C:28]([C:29]2[CH:30]=[N:31][CH:32]=[CH:33][CH:34]=2)=[O:35])=[CH:9][C:8]=1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[CH3:20]

Participants

5

Reactant 3

HCID 884383-Pyridinecarbonyl chloride, hydrochloride (1:1)HCID 516892Sodium BicarbonateHCID 20622819[4-Amino-2-(2-methylphenyl)benzoyl]methionine methyl ester

Product 1

HCID 59926755[4-(3-Pyridylcarbonylamino)-2-(2-methylphenyl)benzoyl]methionine Methyl EsterYield 80%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of the [4-amino-2-(2-methylphenyl)benzoyl]methionine methyl ester (85 mg, 0.23 mmol) in CH2Cl2 (5 mL) was added nicotinic acid chloride hydrochloride (81 mg, 0.46 mmol) and saturated NaHCO3 (2 mL). The reaction was stirred at ambient temperature for 2 hours. The reaction was diluted with CH2Cl2 (10 mL), the layers were separated and the organic layer washed with saturated aqueous NaHCO3 (5 mL), dried (MgSO4) and concentrated in vacuo. Flash chromatography (CH2Cl2-methanol 50:1) and crystallization from ethyl acetate gave the desired compound (87 mg, 80%) as a white powder. 1H NMR (300 MHz, CDCl3) δ 9.10 (dd, 1H, J=2.4, 1.0 Hz), 8.80 (dd, 1H, J=4.7, 1.7 Hz), 8.21 (ddd, 1H, J=7.8, 2.4, 1.7 Hz), 8.09-8.00 (m, 2H), 7.71-7.66 (m, 1H), 7.64-7.61 (m, 1H), 7.46 (ddd, 1H, J=7.8, 4.7, 1.0 Hz), 7.35-7.20 (m, 4H), 5.92 (bd, J=7.5 Hz), 4.67-4.57 (m, 1H), 3.66 (s, 3H), 2.23-2.01 (4 s and m, 8H), 2.00 (m, 1H), 1.65-1.52 (m, 1H). MS m/z 478 (M+1)+.

Workup

  1. customthe layers were separated
  2. washthe organic layer washed with saturated aqueous NaHCO3 (5 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customFlash chromatography (CH2Cl2-methanol 50:1) and crystallization from ethyl acetate

Sources & evidence

ORD record
ord-5ac6a4109b1a4bd0b9289040838e7114
Source dataset
uspto-grants-2004_02
Patent number
US06693123B2

Reaction notes

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