1,8-Diazabicyclo(5.4.0)undec-7-ene → 3-{[7-Cyano-4-hydroxy-7-(pyridin-3-yloxy)-isoquinoline-3-carbonyl]amino}-2-cyclopropyl-propionic acid tert-butyl ester

HRID 1481229Notes

Reaction equation

[C:1]([O:5][C:6](=[O:13])[CH:7]([CH:10]1[CH2:12][CH2:11]1)[CH2:8][NH2:9])([CH3:4])([CH3:3])[CH3:2].C(O[C:17]([C:19]1[N:20]=[C:21](C#N)[C:22]2[C:27]([C:28]=1[OH:29])=[CH:26][CH:25]=[C:24]([O:30][C:31]1[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=1)[CH:23]=2)=[O:18])C.C1CCN2[C:42](=[N:43]CCC2)CC1>CC(N(C)C)=O>[C:1]([O:5][C:6](=[O:13])[CH:7]([CH:10]1[CH2:12][CH2:11]1)[CH2:8][NH:9][C:17]([C:19]1[N:20]=[CH:21][C:22]2[C:27]([C:28]=1[OH:29])=[CH:26][CH2:25][C:24]([C:42]#[N:43])([O:30][C:31]1[CH:32]=[N:33][CH:34]=[CH:35][CH:36]=1)[CH:23]=2)=[O:18])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of 3-amino-2-cyclopropyl-propionic acid tert-butyl ester (39 mg), 1-cyano-4-hydroxy-7-(pyridin-3-yloxy)-isoquinoline-3-carboxylic acid ethyl ester (28 mg) and DBU (0.019 mL) in DMA (0.5 mL) was heated in an oil bath (150° C.) for 1 h. The reaction mixture was then partitioned between EtOAc and diluted HCl solution, EtOAc phase was separated and washed with water, diluted NaCl solution and dried over anhydrous sodium sulfate solution, filtered, concentrated and silica gel column purified to give desired product (21 mg). LC-MS ESI+: 475 (M+1)+.

Workup

customThe reaction mixture was then partitioned between EtOAc and diluted HCl solution, EtOAc phase
customwas separated
washwashed with water, diluted NaCl solution
dry with materialdried over anhydrous sodium sulfate solution
filtrationfiltered
concentrationconcentrated
customsilica gel column purified

Sources & evidence

ORD record: ord-6f0f02f28d1d4b9aa97333ebb94001e3
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409892B2

Reaction notes

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