Dimethylformamide → beta-[[[[4-Cyanophenyl]butyl]amino]carbonyl]aminobenzenepropanoic acid

HRID 2225445Notes

Reaction equation

[N-:1]=[C:2]=O.C(N([CH2:9][CH3:10])CC)C.[NH2:11][C@H:12]([CH2:19][C:20]([OH:22])=[O:21])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[CH3:23][N:24]([CH:26]=[O:27])C>>[C:2]([C:16]1[CH:17]=[CH:18][C:13]([CH2:12][CH2:9][CH2:10][CH2:23][NH:24][C:26]([NH:11][CH:12]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:19][C:20]([OH:22])=[O:21])=[O:27])=[CH:14][CH:15]=1)#[N:1]

Participants

Reactant 4

HCID 6228Dimethylformamide

HCID 8471Triethylamine

HCID 105034Isocyanate

HCID 686703(3R)-3-amino-3-phenylpropanoic acid

Product 1

HCID 54501418beta-[[[[4-Cyanophenyl]butyl]amino]carbonyl]aminobenzenepropanoic acid

Conditions

Temperature: 23 °C

Procedure

A solution of the isocyanate (6) (4.74 mmol), triethylamine (0.479 g, 4.74 mmol), β-phenylalanine (1.17 g, 7.11 mmol), and anhydrous DMF (10 mL) was warmed to 120° C. for 20 hours. After cooling to 23° C., the reaction mixture was concentrated on the rotovap, diluted with ethyl acetate (400 mL), washed with KHSO4 (1N, 2×100 mL), washed with brine (1×100 mL), and dried (Na2SO4). After concentration in vacuo, the urea was purified by flash chromatography (step gradient ethyl acetate with 1% acetic acid to ethyl acetate with 10% methanol and 1% acetic acid) to afford 1.49 g (86%) of(7).

Workup

concentrationthe reaction mixture was concentrated on the rotovap
additiondiluted with ethyl acetate (400 mL)
washwashed with KHSO4 (1N, 2×100 mL)
washwashed with brine (1×100 mL)
dry with materialdried (Na2SO4)
concentrationAfter concentration in vacuo
customthe urea was purified by flash chromatography (step gradient ethyl acetate with 1% acetic acid to ethyl acetate with 10% methanol and 1% acetic acid)
customto afford 1.49 g (86%) of(7)

Sources & evidence

ORD record: ord-c7d9ca83b83444cd9414f53c09849282
Source dataset: uspto-grants-1994_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05344837

Reaction notes

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