Triethylamine → 2-{3-[2-Fluoro-5-(4-oxo-3,4,5,6,7,8-hexahydro-phthalazin-1-ylmethyl)-phenyl]-ureido}-propionic Acid Methyl Ester

HRID 1012956Notes

Reaction equation

[F:1][C:2]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]2[C:21]3[CH2:20][CH2:19][CH2:18][CH2:17][C:16]=3[C:15](=[O:22])[NH:14][N:13]=2)=[CH:7][C:3]=1C(O)=O.C([N:25]([CH2:28]C)CC)C.Cl.[CH3:31][O:32][C:33](=[O:37])[C@H:34]([CH3:36])[NH2:35].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:45])C=CC=CC=1>C(#N)C.CN1CCCC1=O>[CH3:31][O:32][C:33](=[O:37])[CH:34]([NH:35][C:28]([NH:25][C:3]1[CH:7]=[C:8]([CH2:11][C:12]2[C:21]3[CH2:20][CH2:19][CH2:18][CH2:17][C:16]=3[C:15](=[O:22])[NH:14][N:13]=2)[CH:9]=[CH:10][C:2]=1[F:1])=[O:45])[CH3:36]

Participants

Conditions

Temperature: 85 °C

Procedure

To a suspension of 2-fluoro-5-(4-oxo-3,4,5,6,7,8-hexahydro-phthalazin-1-ylmethyl)benzoic acid (11) (0.50 g, 1.650 mmol), in acetonitrile (2.5 ml) was added triethylamine (0.46 ml, 3.31 mmol) the suspension dissolved to afford a brown solution which was subsequently heated to 85° C. D/L alanine methyl ester hydrochloride (2.30 g, 1.650 mmol) dissolved in acetonitrile (5 ml) and N-methylpyrrolidinone (0.5 ml) was added simultaneously to the reaction mixture with diphenylphosphinic azide (0.357 ml, 1.650 mmol). After 40 minutes of heating the reaction mixture was cooled to ambient temperature and concentrated to vacuo. The crude oil was then subjected to flash chromatography, eluent hexane/ethyl acetate, 7:13 (Rf=0.14). Single peak in LC-MS, (0.67 g, 98% purity); m/z (LC-MS, ESP), RT=3.37 mins (M+H 403.2).

Workup

dissolutiondissolved
customto afford a brown solution which
temperatureAfter 40 minutes of heating the reaction mixture
temperaturewas cooled to ambient temperature
concentrationconcentrated to vacuo

Sources & evidence

ORD record: ord-f745de5a42854b289975365c67a7309a
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07981890B2

Reaction notes

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