Acetic Acid → 1-{5-[7-Ethyl-2-(3-ethyl-ureido)-benzothiazol-5-yl]-pyrimidin-2-yl}-4-methyl-piperidine-4-carboxylic acid ethyl ester

HRID 712260Notes

Reaction equation

HRID 712260 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([CH3:35])[CH2:11][CH2:10][N:9]([C:12]2[N:17]=[CH:16][C:15]([C:18]3[CH:19]=[C:20]([CH:33]=[CH2:34])[C:21]4[S:25][C:24]([NH:26][C:27]([NH:29][CH2:30][CH3:31])=[O:28])=[N:23][C:22]=4[CH:32]=3)=[CH:14][N:13]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].C1COCC1.C(O)(=O)C.C([O-])=O.[NH4+]>CCO.[Pd]>[CH2:1]([O:3][C:4]([C:6]1([CH3:35])[CH2:11][CH2:10][N:9]([C:12]2[N:17]=[CH:16][C:15]([C:18]3[CH:19]=[C:20]([CH2:33][CH3:34])[C:21]4[S:25][C:24]([NH:26][C:27]([NH:29][CH2:30][CH3:31])=[O:28])=[N:23][C:22]=4[CH:32]=3)=[CH:14][N:13]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 2723923Ammonium formateHCID 866639721-{5-[2-(3-Ethyl-ureido)-7-vinyl-benzothiazol-5-yl]-pyrimidin-2-yl}-4-methyl-piperidine-4-carboxylic acid ethyl ester

Product 1

HCID 866639731-{5-[7-Ethyl-2-(3-ethyl-ureido)-benzothiazol-5-yl]-pyrimidin-2-yl}-4-methyl-piperidine-4-carboxylic acid ethyl esterYield 70.1%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

1-{5-[2-(3-Ethyl-ureido)-7-vinyl-benzothiazol-5-yl]-pyrimidin-2-yl}-4-methyl-piperidine-4-carboxylic acid ethyl ester (27 mg) was dissolved in EtOH (5 mL), THF (0.5 mL) and acetic acid (0.5 mL) and 10% palladium on carbon (6 mg) and ammonium formate (168 mg) added. The flask was evacuated and purged with N2 (×2) and stirred at 60° C. for four days. The mixture was cooled to rt and filtered through a PTFE filter. The filter was rinsed with EtOH/DCM and the filtrate concentrated under reduced pressure. The residue was then taken up in EtOAc and washed with Na2CO3 (sat, aq). The aqueous layer was washed with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by chromatography, Biotage, 12 g Grace cartridge, DCM to 4% MeOH in DCM and the relevant fractions combined and concentrated under reduced pressure to give the desired product as a white solid (19 mg, 70%). m/z: 497 [M+H]+.

Workup

  1. customThe flask was evacuated
  2. custompurged with N2 (×2)
  3. temperatureThe mixture was cooled to rt
  4. filtrationfiltered through a PTFE
  5. filtrationfilter
  6. washThe filter was rinsed with EtOH/DCM
  7. concentrationthe filtrate concentrated under reduced pressure
  8. washwashed with Na2CO3 (sat, aq)
  9. washThe aqueous layer was washed with EtOAc
  10. washThe combined organic layers were washed with brine
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by chromatography, Biotage, 12 g Grace cartridge, DCM to 4% MeOH in DCM
  14. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-5baf8b459c8345d49bc15f86a9dcace1
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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