Potassium Carbonate → N-[2-chloro-4-(phenoxyacetyl)benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine

HRID 393110Notes

Reaction equation

HRID 393110 reaction equation
[Cl:1][C:2]1[CH:23]=[C:22]([Sn](CCCC)(CCCC)CCCC)[CH:21]=[CH:20][C:3]=1[C:4]([NH:6][C@H:7]([C:17]([OH:19])=[O:18])[CH2:8][NH:9][C:10]([C:12]1[S:13][CH:14]=[CH:15][CH:16]=1)=[O:11])=[O:5].[O:37]([CH2:44][C:45](Cl)=[O:46])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.C(=O)([O-])[O-].[K+].[K+].C(N(C(C)C)CC)(C)C>O1CCCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:1][C:2]1[CH:23]=[C:22]([C:45](=[O:46])[CH2:44][O:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH:21]=[CH:20][C:3]=1[C:4]([NH:6][C@H:7]([C:17]([OH:19])=[O:18])[CH2:8][NH:9][C:10]([C:12]1[S:13][CH:14]=[CH:15][CH:16]=1)=[O:11])=[O:5]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 69703Phenoxyacetyl chlorideHCID 81531DiisopropylethylamineHCID 68819630N-[2-chloro-4-(tri-n-butylstannyl)benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine

Product 1

HCID 60115141N-[2-chloro-4-(phenoxyacetyl)benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of N-[2-chloro-4-(tri-n-butylstannyl)benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine on Wang resin (Example 375; 100 mg), phenoxyacetyl chloride (100 μL, 0.72 mmol), tris(dibenzylidene-acetone)dipalladium(0) (18 mg, 0.02 mmol), potassium carbonate (50 mg, 0.36 mmol) and diisopropylethylamine (100 μL, 0.57 mmol) in tetrahydrofuran (2 mL) was shaken for 2 h, then washed with water, dichloromethane, and methanol. Cleavage was effected by treatment with trifluoroacetic acid/dichloromethane (1:1; 4 mL) and shaking for an hour. The cleavage solution was collected by filtration and the solvent was evaporated. The residue was purified by reverse phase HPLC to give N-[2-chloro-4-(phenoxyacetyl)benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine.

Workup

  1. washwashed with water, dichloromethane, and methanol
  2. stirringshaking for an hour
  3. filtrationThe cleavage solution was collected by filtration
  4. customthe solvent was evaporated
  5. customThe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-1cc19e030f384c4faa605bd3b395027f
Source dataset
uspto-grants-2004_10
Patent number
US06803384B2

Reaction notes

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