1,8-Diazabicyclo(5.4.0)undec-7-ene → 2-Cyclopropyl-3-[(4-hydroxy-7-phenoxy-isoquinoline-3-carbonyl)-amino]propionic acid tert-butyl ester

HRID 1481213Notes

Reaction equation

HRID 1481213 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:15][C:16]([C:18]1[N:19]=[CH:20][C:21]2[C:26]([C:27]=1[OH:28])=[CH:25][CH:24]=[C:23]([O:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH:22]=2)=O.C1CCN2C(=NCCC2)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:16]([C:18]1[N:19]=[CH:20][C:21]2[C:26]([C:27]=1[OH:28])=[CH:25][CH:24]=[C:23]([O:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[CH:22]=2)=[O:15])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 86709142Methyl 4-hydroxy-7-phenoxyisoquinoline-3-carboxylateHCID 89812868Tert-butyl 3-amino-2-cyclopropylpropanoate

Product 1

HCID 898131072-Cyclopropyl-3-[(4-hydroxy-7-phenoxy-isoquinoline-3-carbonyl)-amino]propionic acid tert-butyl esterYield 97.8%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 3-amino-2-cyclopropyl-propionic acid tert-butyl ester (66 mg), 4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid methyl ester (35 mg) and DBU (0.027 mL) in DMA (1 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 as brown solid (52 mg). LC-MS ESI+: 449 (M+1)+.

Workup

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

Sources & evidence

ORD record
ord-0c27736fe2444859bf7798c2d2bedcd2
Source dataset
uspto-grants-2016_08
Patent number
US09409892B2

Reaction notes

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