Diisopropylethylamine → 4-[(2-chloro-5-cyanophenylcarbonyl)amino]-N-[[1-(2-methoxy-ethyl)cyclopentyl]carbonyl]-L-phenylalanine methyl ester

HRID 393472Notes

Reaction equation

HRID 393472 reaction equation
OC(C(F)(F)F)=O.[CH3:8][O:9][C:10](=[O:32])[C@H:11]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:21]([C:23]2[CH:28]=[C:27]([C:29]#[N:30])[CH:26]=[CH:25][C:24]=2[Cl:31])=[O:22])=[CH:16][CH:15]=1)[NH2:12].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:57][O:58][CH2:59][CH2:60][C:61]1([C:66](O)=[O:67])[CH2:65][CH2:64][CH2:63][CH2:62]1.C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C>[CH3:8][O:9][C:10](=[O:32])[C@H:11]([CH2:13][C:14]1[CH:15]=[CH:16][C:17]([NH:20][C:21]([C:23]2[CH:28]=[C:27]([C:29]#[N:30])[CH:26]=[CH:25][C:24]=2[Cl:31])=[O:22])=[CH:18][CH:19]=1)[NH:12][C:66]([C:61]1([CH2:60][CH2:59][O:58][CH3:57])[CH2:65][CH2:64][CH2:63][CH2:62]1)=[O:67]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 223820551-(2-Methoxyethyl)cyclopentane-1-carboxylic acidHCID 1317235094-[(2-chloro-5-cyanophenylcarbonyl)amino]-L-phenylalanine methyl ester TFA salt

Product 1

HCID 541472274-[(2-chloro-5-cyanophenylcarbonyl)amino]-N-[[1-(2-methoxy-ethyl)cyclopentyl]carbonyl]-L-phenylalanine methyl esterYield 88.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-[(2-chloro-5-cyanophenylcarbonyl)amino]-L-phenylalanine methyl ester TFA salt (0.55 mmol, 0.35 g), HBTU (0.65 mmol, 0.24 g) and 1-(2-methoxyethyl)cyclopentane carboxylic acid (0.65 mmol, 0.11 g) in DMF (3 mL) was added diisopropylethylamine (1.65 mmol, 0.29 mL) at room temperature. The clear solution was stirred for 15 h at room temperature and diluted with 50 mL of ethyl acetate. Then, the ethyl acetate layer was washed successively with 0.5N hydrochloric acid (2×20 mL), saturated sodium bicarbonate solution (2×20 mL) and brine solution and was dried over anhydrous magnesium sulfate. Filtration of the drying agent and concentration of the solvent gave a crude product which was purified by silica gel column chromatography to afford 0.25 g (87%) of a white solid: mp 172-175° C. HR MS (C27H30ClN3O5): Obs mass, 512.1949. Calcd mass, 512.1953 (M+H).

Workup

  1. washThen, the ethyl acetate layer was washed successively with 0.5N hydrochloric acid (2×20 mL), saturated sodium bicarbonate solution (2×20 mL) and brine solution
  2. dry with materialwas dried over anhydrous magnesium sulfate
  3. filtrationFiltration of the drying agent and concentration of the solvent
  4. customgave a crude product which
  5. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-b8777ff8855d4ae0a7572dc8f06cf13c
Source dataset
uspto-grants-2004_10
Patent number
US06806365B2

Reaction notes

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