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

HRID 2205890노트

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HRID 2205890 반응식
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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 6386tert-Butanol용매HCID 8857Ethyl Acetate용매

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온도
80 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-a7c20540c027485f805c3d27918d0fa6
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09371319B2

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