Potassium Phosphate, Tribasic → 8-(4-Bromo-2-chloro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester

HRID 2067026ノート

反応式

HRID 2067026 の反応式
[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][N:8]2[CH:11]=[N:12][CH:13]=[C:7]2[C:6]=1Cl)=[O:4].[Br:15][C:16]1[CH:22]=[CH:21][C:19]([NH2:20])=[C:18]([Cl:23])[CH:17]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][N:8]2[CH:11]=[N:12][CH:13]=[C:7]2[C:6]=1[NH:20][C:19]1[CH:21]=[CH:22][C:16]([Br:15])=[CH:17][C:18]=1[Cl:23])=[O:4]

参加物

7

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 6101694-Bromo-2-chloroanilineHCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 59565199Methyl 8-chloroimidazo[1,5-a]pyridine-7-carboxylate

生成物 1

HCID 595652138-(4-Bromo-2-chloro-phenylamino)-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester収率 50%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 1140Toluene溶媒

反応条件

温度
110 °C

実験手順

A suspension of 8-chloro-imidazo[1,5-a]pyridine-7-carboxylic acid methyl ester (300 mg, 1.43 mmol), 4-bromo-2-chloroaniline (354 mg, 1.72 mmol), Pd2dba3 (65 mg, 0.07 mmol), 2-dicyclohexylphosphino-2′,6′-diisopropoxybiphenyl (131 mg, 0.28 mmol) and K3PO4 (424 mg, 2.00 mmol) in toluene (5 ml) was degassed and then heated at 110° C. for 18 hours. The reaction mixture was then cooled to room temperature and diluted with ethyl acetate. The resultant mixture was washed with water and brine, then loaded onto a 10 g Isolute® SCX-2 cartridge which was eluted with methanol and then a 2M solution of ammonia in methanol. The appropriate fractions were combined and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si-PPC, gradient 0% to 100%, ethyl actetate in DCM) to afford the title compound as a yellow oil (271 mg, 50%). LCMS (method B): RT=3.65 min, [M+H]+=381/383.

後処理

  1. customwas degassed
  2. temperatureThe reaction mixture was then cooled to room temperature
  3. additiondiluted with ethyl acetate
  4. washThe resultant mixture was washed with water and brine
  5. washwas eluted with methanol
  6. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-1af585ebf4b54b31aeb5f21a83039607
出典データセット
uspto-grants-2012_10
特許番号
US08293763B2

反応ノート

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