Diisopropylethylamine → HCID 69337249, compound

HRID 844876Notes

Reaction equation

HRID 844876 reaction equation
[CH3:1][O:2][C:3](=[O:24])[C@H:4]([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[C:14](=[O:22])[N:15]([CH3:21])[C:16](=[O:20])[N:17]([CH3:19])[CH:18]=2)=[C:9]([CH3:23])[CH:8]=1)[NH2:5].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl:49][C:50]1[CH:58]=[CH:57][CH:56]=[C:55]([CH3:59])[C:51]=1[C:52](O)=[O:53].C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:24])[C@H:4]([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[C:14](=[O:22])[N:15]([CH3:21])[C:16](=[O:20])[N:17]([CH3:19])[CH:18]=2)=[C:9]([CH3:23])[CH:8]=1)[NH:5][C:52]([C:51]1[C:55]([CH3:59])=[CH:56][CH:57]=[CH:58][C:50]=1[Cl:49])=[O:53]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 888702-Chloro-6-methylbenzoic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 69336446HCID 69336446, compound

Product 1

HCID 69337249HCID 69337249, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 4-(1,3-dimethyl-2,4-dioxo-5-pyrimidinyl)-3-methyl-L-phenylalanine methyl ester (0.125 mmol, 46 mg), HBTU (0.125 mmol, 47.5 mg) and 2-chloro-6-methylbenzoic acid (0.137 mmol, 25 mg) in DMF (2 mL) was added diisopropylethylamine (0.312 mmol, 44 uL) at room temperature. After 5 min, everything went into solution and the clear yellow solution was stirred for 72 h at room temperature. The resulting dark-brown solution was diluted with ethyl acetate (30 mL). The ethyl acetate layer was washed successively with 1N hydrochloric acid (2×30 mL), saturated sodium bicarbonate solution (30 mL), and brine solution (30 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 42 mg (70% yield) of N-[(2-chloro-6-methylphenyl)carbonyl]-4-(1,3-dimethyl-2,4-dioxo-5-pyrimidinyl)-3-methyl-L-phenylalanine methyl ester as a oily residue. ES-HRMS m/e calcd for C25H26ClN3O5 (M+Na) 506.1454, found 506.1459.

Workup

  1. washThe ethyl acetate layer was washed successively with 1N hydrochloric acid (2×30 mL), saturated sodium bicarbonate solution (30 mL), and brine solution (30 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-808f2bb4833141ce99640781ef029076
Source dataset
uspto-grants-2002_04
Patent number
US06380387B1

Reaction notes

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