Trifluoroacetic acid → HCID 86712305, compound

HRID 592406Notes

Reaction equation

HRID 592406 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2(C(N)=O)[CH2:18][CH2:17]2)[C:5]([Cl:22])=[CH:4][N:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[NH2:29][C:30]1[CH:34]=[C:33]([CH3:35])[N:32](C(OC(C)(C)C)=O)[N:31]=1.NC1[N:48]([C:49](OC(C)(C)C)=[O:50])N=C(C)C=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(O)(C(F)(F)F)=O.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[Cl:22][C:5]1[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH:16]2[CH2:17][CH:18]2[C:49]([NH2:48])=[O:50])=[N:7][C:2]([NH:29][C:30]2[CH:34]=[C:33]([CH3:35])[NH:32][N:31]=2)=[N:3][CH:4]=1

Participants

12

Reactant 7

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 113215371H-Pyrazole-1-carboxylicacid,3-amino-5-methyl-,1,1-dimethylethylesterHCID 56972293tert-Butyl 5-amino-3-methyl-1H-pyrazole-1-carboxylateHCID 867122951-(2-(2-(2,5-Dichloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

Product 1

HCID 86712305HCID 86712305, compoundYield 3%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

A suspension of 1-(2-(2-(2,5-dichloropyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide A14 (263 mg, 0.781 mmol), Cs2CO3 (509 mg, 1.56 mmol) and a mixture of tert-butyl 3-amino-5-methyl-1H-pyrazole-1-carboxylate and tert-butyl 5-amino-3-methyl-1H-pyrazole-1-carboxylate A27 (154 mg, 0.781 mmol) in 1,4-dioxane (5 mL) was sonicated for 10 minutes. Xantphos (23 mg, 0.039 mmol) and Pd2(dba)3 (36 mg, 0.039 mmol) were added and the mixture was irradiated in the microwave at 120° C. for 20 minutes. The resulting mixture was adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) to give a yellow oil which was dissolved in DCM (5.0 mL). TFA (1.0 mL) was added and the mixture was stirred at room temperature for 2 hours before the addition of sat. aq. Na2CO3 (20 mL) and water (100 mL). The resultant precipitate was collected by filtration, adsorbed onto silica gel and purified by silica gel column chromatography (Biotage Isolera, 12 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C. then 0-30% MeOH in EtOAc) to give the title compound 27 as a yellow solid (8 mg, 3%). LCMS-A: rt 5.412 min; m/z 397.2 [M+H]+.

Workup

  1. customwas sonicated for 10 minutes
  2. customthe mixture was irradiated in the microwave at 120° C. for 20 minutes
  3. custompurified by column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.)
  4. customto give a yellow oil which
  5. filtrationThe resultant precipitate was collected by filtration
  6. custompurified by silica gel column chromatography (Biotage Isolera, 12 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.

Sources & evidence

ORD record
ord-9c36246a26e14916ab0a084283dcb0a3
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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