Trifluoroacetic acid → HCID 86712305、化合物

HRID 592406ノート

反応式

HRID 592406 の反応式
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

参加物

12

反応物 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

生成物 1

HCID 86712305HCID 86712305、化合物収率 3%

試薬・触媒・溶媒 4

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 312751,4-Dioxane溶媒

実験手順

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]+.

後処理

  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.

出典と根拠

ORDレコード
ord-9c36246a26e14916ab0a084283dcb0a3
出典データセット
uspto-grants-2016_01
特許番号
US09238644B2

反応ノート

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