Diisopropylethylamine → 4-[[(2,6-Dichlorophenyl)Carbonyl]Amino]-N-[[1-(2-Methoxyethyl)-Cyclopentyl]Carbonyl]-L-Phenylalanine Methyl Ester

HRID 393488Notes

Reaction equation

HRID 393488 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:25])[C@H:5]([CH2:7][C:8]1[CH:13]=[CH:12][C:11]([NH:14][C:15]([C:17]2[C:22]([Cl:23])=[CH:21][CH:20]=[CH:19][C:18]=2[Cl:24])=[O:16])=[CH:10][CH:9]=1)[NH2:6].[CH3:26][O:27][CH2:28][CH2:29][C:30]1([C:35](O)=[O:36])[CH2:34][CH2:33][CH2:32][CH2:31]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C>[CH3:2][O:3][C:4](=[O:25])[C@H:5]([CH2:7][C:8]1[CH:9]=[CH:10][C:11]([NH:14][C:15]([C:17]2[C:22]([Cl:23])=[CH:21][CH:20]=[CH:19][C:18]=2[Cl:24])=[O:16])=[CH:12][CH:13]=1)[NH:6][C:35]([C:30]1([CH2:29][CH2:28][O:27][CH3:26])[CH2:34][CH2:33][CH2:32][CH2:31]1)=[O:36]

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 23383932methyl (2S)-2-amino-3-{4-[(2,6-dichlorobenzoyl)amino]phenyl}propionate hydrochloride

Product 1

HCID 539042644-[[(2,6-Dichlorophenyl)Carbonyl]Amino]-N-[[1-(2-Methoxyethyl)-Cyclopentyl]Carbonyl]-L-Phenylalanine Methyl EsterYield 84.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-[[(2,6-dichlorophenyl)carbonyl]amino]-L-phenylalanine methyl ester hydrochloride salt (43.03 mmol, 11.75 g) and 1-(2-methoxyethyl)cyclopentane carboxylic acid (43.5 mmol, 7.5 g) in DMF (130 mL) was added HBTU (43.5 mmol, 16.5 g) and diisopropylethylamine (108.8 mmol, 19.02 mL) at room temperature. The clear solution was stirred 23 h at room temperature and was diluted with 200 mL of ethyl acetate. The ethyl acetate layer was washed successively with 0.5 N hydrochloric acid (2×100 mL), saturated sodium bicarbonate solution (2×100 mL), brine solution and was dried over anhydrous magnesium sulfate. Filtration of the drying agent and concentration of the solvent gave 18.86 g (84%) of a white solid, mp 85-87° C. 1H NMR (DMSO-d6) (400 MHz) δ 10.65 (s, 1H), 7.88 (d, 1H, J=19 Hz), 7.47-7.59 (m, 5H), 7.21 (d, 2H, J=19 Hz), 4.47-4.53 (m, 1H), 3.64 (s, 3H), 2.88-3.1 (m, 7H), 1.76-1.98 (m, 4H), 1.23-1.47 (m, 6H). HR MS C26H30Cl2N2O5): Obs. mass, 521.1586. Calcd. mass, 521.1610 (M+H).

Workup

  1. washThe ethyl acetate layer was washed successively with 0.5 N hydrochloric acid (2×100 mL), saturated sodium bicarbonate solution (2×100 mL), brine solution
  2. dry with materialwas dried over anhydrous magnesium sulfate
  3. filtrationFiltration of the drying agent and concentration of the solvent

Sources & evidence

ORD record
ord-db387b713f5e4377896ec5ee4392d7c6
Source dataset
uspto-grants-2004_10
Patent number
US06806365B2

Reaction notes

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