Water → RO-0506997

HRID 844893Notes

Reaction equation

HRID 844893 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]([NH:11][C@H:12]([C:31]([OH:33])=[O:32])[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[C:21](=[O:30])[N:22]([CH3:29])[C:23](=[O:28])[N:24]([CH3:27])[C:25]=2[CH3:26])=[CH:16][CH:15]=1)=[O:10].C(=O)(O)[O-].[Na+].I[CH2:40][CH3:41].O>CN(C=O)C>[CH2:40]([O:32][C:31](=[O:33])[C@H:12]([CH2:13][C:14]1[CH:15]=[CH:16][C:17]([C:20]2[C:21](=[O:30])[N:22]([CH3:29])[C:23](=[O:28])[N:24]([CH3:27])[C:25]=2[CH3:26])=[CH:18][CH:19]=1)[NH:11][C:9]([C:3]1[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=1[F:8])=[O:10])[CH3:41]

Participants

6

Reactant 4

HCID 962WaterHCID 6340IodoethaneHCID 516892Sodium BicarbonateHCID 69337579CH9Z955RV6

Product 1

HCID 10277800RO-0506997Yield 93%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of N-[(2,6-difluorophenyl)carbonyl]-4-(1,3,6-trimethyl-2,4-dioxo-5-pyrimidinyl)-L-phenylalanine (0.743 mmol, 340 mg) and sodium bicarbonate (5.94 mmol, 499 mg) in DMF (3.8 mL) was added iodoethane (5.94 mmol, 0.475 mL) at room temperature. The mixture was stirred for 48 h at room temperature. Then, the reaction mixture was poured into water (100 mL) and was extracted with ethyl acetate (3×25 mL). The combined extracts were washed with brine solution (80 mL) and were dried over anhydrous sodium sulfate. Filtration of the drying agent and concentration of the filtrate gave the crude product which was purified by silica gel chromatography using a Biotage (40s) column to obtain 335 mg (93% yield) of N-[(2,6-difluorophenyl)carbonyl]-4-(1,3,6-trimethyl-2,4-dioxo-5-pyrimidinyl)-L-phenylalanine ethyl ester as a crystalline white solid: mp 218-219° C. ES-HRMS m/e calcd for C25H25F2N3O5 (M+Na) 508.1654, found 508.1660.

Workup

  1. extractionwas extracted with ethyl acetate (3×25 mL)
  2. washThe combined extracts were washed with brine solution (80 mL)
  3. dry with materialwere dried over anhydrous sodium sulfate
  4. filtrationFiltration of the drying agent and concentration of the filtrate
  5. customgave the crude product which
  6. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-7b6e6f611f3f43eeba0ca7e37602e981
Source dataset
uspto-grants-2002_04
Patent number
US06380387B1

Reaction notes

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