HCID 59293924, compound → HCID 86641183, compound

HRID 1930785Notes

Reaction equation

HRID 1930785 reaction equation
[CH3:1][N:2]([CH3:29])[CH2:3][CH2:4][O:5][C:6](=[O:28])[C@@H:7]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:8][CH2:9][C:10]([O:12]CC1C=CC=CC=1)=[O:11]>[C].[Pd].C(O)C>[CH3:29][N:2]([CH3:1])[CH2:3][CH2:4][O:5][C:6](=[O:28])[C@@H:7]([NH:20][C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])[CH2:8][CH2:9][C:10]([OH:12])=[O:11]

Participants

4

Reactant 1

HCID 59293924HCID 59293924, compound

Product 1

HCID 86641183HCID 86641183, compoundYield 134.6%

Reagents, catalysts & solvents 2

HCID 178418390HCID 178418390, compoundCatalystHCID 702EthanolSolvent

Procedure

To a mixture of (S)-2-tert-butoxycarbonylamino-pentanedioic acid 5-benzyl ester 1-(2-dimethylamino-ethyl)ester (370 mg, 0.70 mmol; 77% purity) described in Manufacturing Example 3-1 and ethanol (4 mL) was added palladium-carbon (40 mg, 0.19 mmol; 50% water content) at room temperature, which was stirred overnight at room temperature under a hydrogen atmosphere (1 atm). The reaction mixture was replaced with nitrogen and filtered through a Celite pad. The solvent was evaporated under a reduced pressure, so as to obtain (S)-2-tert-butoxycarbonylamino-pentanedioic acid 1-(2-dimethylamino-ethyl)ester (300 mg) in a crude form. The crude product thus obtained was used directly in the next reaction. To a mixture of 3-(3-(4-(pyridin-2-yloxymethyl)-benzyl)-isoxazol-5-yl)-pyridin-2-ylamine (150 mg, 0.42 mmol) described in Reference Example 1 and acetonitrile (3 mL) were added (S)-2-tert-butoxycarbonylamino-pentanedioic acid 1-(2-dimethylamino-ethyl)ester (crude, 190 mg) and O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl-uronium hexafluorophosphate (160 mg, 0.42 mmol) in this order at 0° C., which was stirred overnight at room temperature. Water was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated under a reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=30:1), so as to obtain the titled compound (56 mg, purity of 75%).

Workup

  1. filtrationfiltered through a Celite pad
  2. customThe solvent was evaporated under a reduced pressure

Sources & evidence

ORD record
ord-b1df49c4cc9e4cbd81554bd9735e2c58
Source dataset
uspto-grants-2012_05
Patent number
US08188119B2

Reaction notes

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