Potassium Phosphate, Tribasic → N-[6-(3,6-Dihydro-2H-pyran-4-yl)-5-methylpyridin-3-yl]-5-methyl-1-[4-(trifluoromethyl)-phenyl]-1H-pyrazole-4-carboxamide

HRID 1748634ノート

反応式

HRID 1748634 の反応式
[CH3:1][C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[CH:9][CH:8]=2)[N:5]=[CH:4][C:3]=1[C:17]([NH2:19])=[O:18].Br[C:21]1[CH:22]=[C:23]([CH3:33])[C:24]([C:27]2[CH2:28][CH2:29][O:30][CH2:31][CH:32]=2)=[N:25][CH:26]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(O)(C)(C)C.C(Cl)(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].C(P(C(C)(C)C)C1C(C)=C(C)C(C)=C(C)C=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C>[O:30]1[CH2:31][CH:32]=[C:27]([C:24]2[N:25]=[CH:26][C:21]([NH:19][C:17]([C:3]3[CH:4]=[N:5][N:6]([C:7]4[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:14])[F:15])=[CH:9][CH:8]=4)[C:2]=3[CH3:1])=[O:18])=[CH:22][C:23]=2[CH3:33])[CH2:28][CH2:29]1

参加物

8

反応物 3

HCID 62657Potassium Phosphate, TribasicHCID 178227615-methyl-1-[4-(trifluoromethyl)phenyl]-1H-pyrazole-4-carboxamideHCID 866925085-Bromo-2-(3,6-dihydro-2H-pyran-4-yl)-3-methylpyridine

生成物 1

HCID 86692571N-[6-(3,6-Dihydro-2H-pyran-4-yl)-5-methylpyridin-3-yl]-5-methyl-1-[4-(trifluoromethyl)-phenyl]-1H-pyrazole-4-carboxamide収率 58%

試薬・触媒・溶媒 4

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 11953610Di-tert-butyl[3,4,5,6-tetramethyl-2',4',6'-tris(propan-2-yl)-[1,1'-biphenyl]-2-yl]phosphane触媒HCID 6212Chloroform溶媒HCID 6386tert-Butanol溶媒

反応条件

温度
110 °C

実験手順

A suspension of 5-methyl-1-[4-(trifluoromethyl)phenyl]-1H-pyrazole-4-carboxamide (212 mg), 5-bromo-2-(3,6-dihydro-2H-pyran-4-yl)-3-methylpyridine (200 mg) described in Reference Example 135, 2-(di-tert-butylphosphino)-3,4,5,6-tetramethyl-2′,4′,6′-triisopropyl-1,1′-biphenyl (19 mg), tris(dibenzylideneacetone)dipalladium (0) (7.2 mg) and tripotassium phosphate (200 mg) in tert-butanol (3 ml) was stirred at 110° C. After the reaction, the reaction solution was left stand, diluted with chloroform and filtered through Celite. The organic layer was washed with water and saturated brine successively, dried over anhydrous sodium sulfate and concentrated. The resulting residue was purified with a silica gel column chromatography (chloroform/methanol), washed with hot ethanol and the resulting solid was filtered and dried at 60° C. in vacuo to give the titled compound (202 mg) as a white solid.

後処理

  1. customAfter the reaction
  2. waitthe reaction solution was left stand
  3. filtrationfiltered through Celite
  4. washThe organic layer was washed with water and saturated brine successively
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customThe resulting residue was purified with a silica gel column chromatography (chloroform/methanol)
  8. washwashed with hot ethanol
  9. filtrationthe resulting solid was filtered
  10. customdried at 60° C. in vacuo

出典と根拠

ORDレコード
ord-0436c03475aa45f292880c1dbd83ddd1
出典データセット
uspto-grants-2015_10
特許番号
US09150555B2

反応ノート

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