HCID 86712347, compound → HCID 86712346, compound

HRID 592484Notes

Reaction equation

HRID 592484 reaction equation
[C:1]([C:4]1([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[C:13]#[C:14][C:15]2[C:20]([C:21]([F:24])([F:23])[F:22])=[CH:19][N:18]=[C:17]([NH:25][C:26]3[CH:27]=[N:28][N:29]([CH:31]4[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:33][CH2:32]4)[CH:30]=3)[N:16]=2)[CH2:6][CH2:5]1)(=[O:3])[NH2:2]>CCOC(C)=O.CO.[Pd]>[C:1]([C:4]1([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[CH2:13][CH2:14][C:15]2[C:20]([C:21]([F:24])([F:22])[F:23])=[CH:19][N:18]=[C:17]([NH:25][C:26]3[CH:27]=[N:28][N:29]([CH:31]4[CH2:36][CH2:35][N:34]([C:37]([O:39][C:40]([CH3:41])([CH3:42])[CH3:43])=[O:38])[CH2:33][CH2:32]4)[CH:30]=3)[N:16]=2)[CH2:6][CH2:5]1)(=[O:3])[NH2:2]

Participants

5

Reactant 1

HCID 86712347HCID 86712347, compound

Product 1

HCID 86712346HCID 86712346, compound

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of tert-butyl 4-(4-((4-((2-(1-carbamoylcyclopropyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)piperidine-1-carboxylate A76 (0.405 g, 0.680 mmol) and 10% Pd/C (wetted with ca. 53% water, 0.200 g) in EtOAc (30 mL) and MeOH (15 mL) was stirred under an atmosphere of H2 at room temperature for 16 hours. The mixture was filtered through a plug of Celite and the filtrate was concentrated in vacuo. Purification by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-10% MeOH in DCM) gave a yellow oil which was further purified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 10-90% EtOAc in petroleum benzine 40-60° C.) to give the title compound A77 as a yellow solid (0.213 g, 52%). LCMS-D: rt 3.62 min; m/z 600 [M+H]+.

Workup

  1. filtrationThe mixture was filtered through a plug of Celite
  2. concentrationthe filtrate was concentrated in vacuo
  3. customPurification by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-10% MeOH in DCM)
  4. customgave a yellow oil which
  5. customwas further purified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 10-90% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-4065b19706534c0bb7a5a6bbe8892484
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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