2,6-Dichlorobenzoyl chloride → N-[(2,6-dichlorophenyl)carbonyl]-4-(1,3,6-trimethyl-2,4-dioxo-5-pyrimidinyl)-L-phenylalanine 1-(acetoxy)ethyl ester

HRID 844891Notes

Reaction equation

HRID 844891 reaction equation
Cl.[C:2]([O:5][CH:6]([O:8][C:9](=[O:30])[C@H:10]([CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[C:20](=[O:29])[N:21]([CH3:28])[C:22](=[O:27])[N:23]([CH3:26])[C:24]=2[CH3:25])=[CH:15][CH:14]=1)[NH2:11])[CH3:7])(=[O:4])[CH3:3].[Cl:31][C:32]1[CH:40]=[CH:39][CH:38]=[C:37]([Cl:41])[C:33]=1[C:34](Cl)=[O:35].C(N(C(C)C)CC)(C)C>ClCCl>[C:2]([O:5][CH:6]([O:8][C:9](=[O:30])[C@H:10]([CH2:12][C:13]1[CH:14]=[CH:15][C:16]([C:19]2[C:20](=[O:29])[N:21]([CH3:28])[C:22](=[O:27])[N:23]([CH3:26])[C:24]=2[CH3:25])=[CH:17][CH:18]=1)[NH:11][C:34]([C:33]1[C:32]([Cl:31])=[CH:40][CH:39]=[CH:38][C:37]=1[Cl:41])=[O:35])[CH3:7])(=[O:4])[CH3:3]

Participants

5

Reactant 3

HCID 783922,6-Dichlorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 693358364-(1,3,6-trimethyl-2,4-dioxo-5-pyrimidinyl)-L-phenylalanine 1-(acetoxy)ethyl ester hydrochloride

Product 1

HCID 10166979N-[(2,6-dichlorophenyl)carbonyl]-4-(1,3,6-trimethyl-2,4-dioxo-5-pyrimidinyl)-L-phenylalanine 1-(acetoxy)ethyl esterYield 74.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of 4-(1,3,6-trimethyl-2,4-dioxo-5-pyrimidinyl)-L-phenylalanine 1-(acetoxy)ethyl ester hydrochloride salt (0.723 mmol, 399 mg) and 2,6-dichlorobenzoyl chloride (0.8 mmol, 0.17 g) in dichloromethane (5 mL) was added diisopropylethylamine (3.2 mmol, 0.45 mL) at room temperature. After 5 min, everything went into solution and the clear yellow solution was stirred for 48 h at room temperature. The resulting light brown solution was diluted with dichloromethane (50 mL). The dichloromethane layer was washed successively with 1N hydrochloric acid (2×50 mL), saturated sodium bicarbonate solution (50 mL), and brine solution (50 mL) and was dried over anhydrous magnesium sulfate. Filtration of the drying agent and concentration of the solvent gave the crude product, which was purified by silica gel chromatography using a Biotage (40s) column to afford 0.312 g (67% yield) of N-[(2,6-dichlorophenyl)carbonyl]-4-(1,3,6-trimethyl-2,4-dioxo-5-pyrimidinyl)-L-phenylalanine 1-(acetoxy)ethyl ester as a white solid: mp 168-170° C. ES-HRMS m/e calcd for C27H27Cl2N3O7 (M+Na) 598.1118, found 598.1122.

Workup

  1. washThe dichloromethane layer was washed successively with 1N hydrochloric acid (2×50 mL), saturated sodium bicarbonate solution (50 mL), and brine solution (50 mL)
  2. dry with materialwas dried over anhydrous magnesium sulfate
  3. filtrationFiltration of the drying agent and concentration of the solvent
  4. customgave the crude product, which
  5. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-6503b0193c844046a0ee113111140864
Source dataset
uspto-grants-2002_04
Patent number
US06380387B1

Reaction notes

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