Oxalyl chloride → HCID 12042614, compound

HRID 1018153Notes

Reaction equation

HRID 1018153 reaction equation
[CH3:1][C:2]1[C:7]([C:8]([OH:10])=O)=[C:6]([CH3:11])[CH:5]=[CH:4][N:3]=1.C(Cl)(=O)C(Cl)=O.[CH3:18][O:19][C:20](=[O:46])[C@H:21]([CH2:38][C:39]1[CH:44]=[CH:43][C:42]([NH2:45])=[CH:41][CH:40]=1)[NH:22][C:23]([C:25]1([CH2:30][CH2:31][CH2:32][CH2:33][S:34]([CH3:37])(=[O:36])=[O:35])[CH2:29][CH2:28][CH2:27][CH2:26]1)=[S:24].C(N(C(C)C)CC)(C)C>ClCCl.CN(C=O)C.O>[CH3:18][O:19][C:20](=[O:46])[C@H:21]([CH2:38][C:39]1[CH:44]=[CH:43][C:42]([NH:45][C:8]([C:7]2[C:2]([CH3:1])=[N:3][CH:4]=[CH:5][C:6]=2[CH3:11])=[O:10])=[CH:41][CH:40]=1)[NH:22][C:23]([C:25]1([CH2:30][CH2:31][CH2:32][CH2:33][S:34]([CH3:37])(=[O:36])=[O:35])[CH2:29][CH2:28][CH2:27][CH2:26]1)=[S:24]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 15125612,4-Dimethyl-3-pyridinecarboxylic acidHCID 54107824HCID 54107824, compound

Product 1

HCID 12042614HCID 12042614, compoundYield 65%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

To an ice cold solution of 2,4-dimethyl-3-pyridinecarboxylic acid (0.3 mmol, 45 mg) in dichloromethane (2 mL) containing one drop of DMF, was added oxalyl chloride (0.39 mmol, 49.5 mg) at 0° C. The reaction mixture was stirred for 30 min at this temperature, was allowed to warm to room temperature and was stirred for an additional 2 h. The solution was concentrated and the residue was dried under high vacuum. To a mixture of above acid chloride and 4-amino-N-[[1-[4-(methylsulfonyl)butyl]cyclopentyl]thioxomethyl]-L-phenylalanine methyl ester (0.2 mmol, 88 mg) in dichloromethane (3 mL) was added diisopropylethylamine (1 mmol, 0.175 mL) at room temperature. After the solution had stirred for 15 h, TLC analysis of the mixture did not detect any starting material remaining. The solution was diluted with water (20 mL) and dichloromethane (20 mL) and the layers were separated. The aqueous phase was extracted with dichloromethane (10 mL) and the combined organic extracts were washed with brine (300 mL). The dried (MgSO4) solution was filtered and evaporated to dryness and the residual material was purified by RP-HPLC to obtain 74 mg (65%) of 4-[[(2,4-dimethylpyridin-3-yl)carbonyl]amino]-N-[[1-[4-(methylsulfonyl)butyl]cyclopentyl]thioxomethyl]-L-phenylalanine methyl ester as an amorphous colorless solid. HRMS: Obs. mass, 574.2389. Calcd. mass, 574.2409 (M+H).

Workup

  1. stirringwas stirred for an additional 2 h
  2. concentrationThe solution was concentrated
  3. customthe residue was dried under high vacuum
  4. stirringAfter the solution had stirred for 15 h
  5. customthe layers were separated
  6. extractionThe aqueous phase was extracted with dichloromethane (10 mL)
  7. washthe combined organic extracts were washed with brine (300 mL)
  8. dry with materialThe dried (MgSO4) solution
  9. filtrationwas filtered
  10. customevaporated to dryness
  11. customthe residual material was purified by RP-HPLC

Sources & evidence

ORD record
ord-eefe8920ff65467584a83fbc6bdc4a22
Source dataset
uspto-grants-2002_11
Patent number
US06479666B2

Reaction notes

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