(S)-8-(2-amino-6-((R)-1-(4-((E)-3-ethoxy-3-oxoprop-1-en-1-yl)-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2-((((2E,4Z)-2-vinylhexa-2,4-dien-1-yl)oxy)carbonyl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid → (S)-8-(2-amino-6-((R)-1-(4-(3-ethoxy-3-oxopropyl)-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid

HRID 1499149Notes

Reaction equation

HRID 1499149 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:31][CH2:30][C:11]3([CH2:15][N:14](C(OC/C(/C=C)=C/C=C\C)=O)[C@H:13]([C:27]([OH:29])=[O:28])[CH2:12]3)[CH2:10][CH2:9]2)[CH:5]=[C:4]([O:32][C@H:33]([C:38]2[CH:43]=[CH:42][C:41](/[CH:44]=[CH:45]/[C:46]([O:48][CH2:49][CH3:50])=[O:47])=[CH:40][C:39]=2[N:51]2[CH:55]=[CH:54][C:53]([CH3:56])=[N:52]2)[C:34]([F:37])([F:36])[F:35])[N:3]=1>CO.[Pd]>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:31][CH2:30][C:11]3([CH2:15][NH:14][C@H:13]([C:27]([OH:29])=[O:28])[CH2:12]3)[CH2:10][CH2:9]2)[CH:5]=[C:4]([O:32][C@H:33]([C:38]2[CH:43]=[CH:42][C:41]([CH2:44][CH2:45][C:46]([O:48][CH2:49][CH3:50])=[O:47])=[CH:40][C:39]=2[N:51]2[CH:55]=[CH:54][C:53]([CH3:56])=[N:52]2)[C:34]([F:37])([F:36])[F:35])[N:3]=1

Participants

4

Reactant 1

HCID 117952361(S)-8-(2-amino-6-((R)-1-(4-((E)-3-ethoxy-3-oxoprop-1-en-1-yl)-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2-((((2E,4Z)-2-vinylhexa-2,4-dien-1-yl)oxy)carbonyl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid

Product 1

HCID 117952855(S)-8-(2-amino-6-((R)-1-(4-(3-ethoxy-3-oxopropyl)-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a solution of ((S)-8-(2-amino-6-((R)-1-(4-((E)-3-ethoxy-3-oxoprop-1-en-1-yl)-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)-2-((((2E,4Z)-2-vinylhexa-2,4-dien-1-yl)oxy)carbonyl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid (180 mg, 0.15 mmol) in MeOH (5 mL) was hydrogenated in an H-Cube apparatus using a 10% (w/w) Pd/C cartridge with a flow rate of 1.0 mL/min at RT. The resulting eluent was concentrated in vacuo and the product was purified by column chromatography using an Isco Gold reversed phase silica cartridge (100% CH2Cl2 to 90:9:1 CH2Cl2:MeOH:conc. NH4OH) to provide the title compound as a white solid.

Workup

  1. customat RT
  2. concentrationThe resulting eluent was concentrated in vacuo
  3. customthe product was purified by column chromatography

Sources & evidence

ORD record
ord-8e235e7d579e413da1ac7d841623061c
Source dataset
uspto-grants-2015_12
Patent number
US09199994B2

Reaction notes

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