Water → tert-Butyl 4-(6-(4-fluorophenylamino)-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazole-1-carboxylate

HRID 2205890ノート

反応式

HRID 2205890 の反応式
Cl[C:2]1[N:7]=[CH:6][C:5]2[CH:8]=[C:9]([C:15]3[CH:16]=[N:17][N:18]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH:19]=3)[N:10]([S:11]([CH3:14])(=[O:13])=[O:12])[C:4]=2[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[F:33][C:34]1[CH:40]=[CH:39][C:37]([NH2:38])=[CH:36][CH:35]=1.O>CC(O)(C)C.CCOC(C)=O.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]>[F:33][C:34]1[CH:40]=[CH:39][C:37]([NH:38][C:2]2[N:7]=[CH:6][C:5]3[CH:8]=[C:9]([C:15]4[CH:16]=[N:17][N:18]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH:19]=4)[N:10]([S:11]([CH3:14])(=[O:13])=[O:12])[C:4]=3[CH:3]=2)=[CH:36][CH:35]=1

参加物

8

反応物 4

HCID 962WaterHCID 97314-FluoroanilineHCID 10796Cesium carbonateHCID 86706273tert-Butyl 4-(6-chloro-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazole-1-carboxylate

生成物 1

HCID 86706303tert-Butyl 4-(6-(4-fluorophenylamino)-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazole-1-carboxylate収率 42%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 6386tert-Butanol溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
80 °C

実験手順

Pd2(dba)3 (9.2 mg, 0.01 mmol) was added to a mixture of tert-butyl 4-(6-chloro-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazole-1-carboxylate (15) (40 mg, 0.101 mmol), cesium carbonate (131 mg, 0.403 mmol), 4-fluoroaniline (19 μL, 0.202 mmol) and di-tBuX-Phos (17.1 mg, 0.040 mmol) in t-BuOH containing water (3%) (1.1 mL). The reaction mixture was heated at 80° C. for 1.5 hr under microwave irradiation. It was then diluted with EtOAc and washed with water. The organic extracts were dried over MgSO4, filtered and concentrated under vacuum. The residue was then purified by prep TLC (DCM/MeOH, 95/5) to afford 20 mg of title compound mixed with some starting material. This mixture was used in the next step without further purification. 1H NMR (500 MHz, CDCl3) 1.69 (s, 9H), 2.90 (s, 3H), 6.69 (d, J=0.9 Hz, 1H), 7.05-7.09 (m, 2H), 7.33-7.37 (m, 2H), 7.46 (br m, 1H), 7.93 (d, J=0.9 Hz, 1H), 8.35 (d, J=0.9 Hz, 1H), 8.48 (m, 1H).

後処理

  1. washwashed with water
  2. dry with materialThe organic extracts were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customThe residue was then purified by prep TLC (DCM/MeOH, 95/5)

出典と根拠

ORDレコード
ord-a7c20540c027485f805c3d27918d0fa6
出典データセット
uspto-grants-2016_06
特許番号
US09371319B2

反応ノート

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