Cesium carbonate → Ethyl 2-(3-cyano-6-(isoquinolin-3-ylamino)pyrazin-2-yloxy)acetate

HRID 40690

반응식

HRID 40690 반응식
CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.Cl[C:44]1[N:45]=[CH:46][C:47]2[C:52]([CH:53]=1)=[CH:51][CH:50]=[CH:49][CH:48]=2.C(=O)([O-])[O-].[Cs+].[Cs+].[NH2:60][C:61]1[N:66]=[C:65]([O:67][CH2:68][C:69]([O:71][CH2:72][CH3:73])=[O:70])[C:64]([C:74]#[N:75])=[N:63][CH:62]=1>C1(C)C=CC=CC=1.CN(C=O)C.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].CCOCC>[C:74]([C:64]1[C:65]([O:67][CH2:68][C:69]([O:71][CH2:72][CH3:73])=[O:70])=[N:66][C:61]([NH:60][C:44]2[N:45]=[CH:46][C:47]3[C:52]([CH:53]=2)=[CH:51][CH:50]=[CH:49][CH:48]=3)=[CH:62][N:63]=1)#[N:75]

참가 물질

9

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 6409683-ChloroisoquinolineHCID 59636444Ethyl 2-(6-amino-3-cyanopyrazin-2-yloxy)acetate

생성물 1

HCID 44204747Ethyl 2-(3-cyano-6-(isoquinolin-3-ylamino)pyrazin-2-yloxy)acetate수율 25%

시약·촉매·용매 4

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매HCID 3283Diethyl Ether용매HCID 6228Dimethylformamide용매

반응 조건

온도
100 °C

실험 절차

A mixture of tris(dibenzylideneacetone)dipalladium (0) (39 mg, 0.043 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (50 mg, 0.086 mmol) in toluene (1.5 mL) and DMF (1.5 mL) was degassed under a stream of nitrogen gas with stirring for 15 minutes. 3-Chloroisoquinoline (70 mg, 0.428 mmol), caesium carbonate (279 mg, 0.856 mmol) and ethyl 2-(6-amino-3-cyanopyrazin-2-yloxy)acetate (105 mg, 0.471 mmol) were added and the mixture was degassed for a further 5 minutes. The mixture was then heated at 100° C. for 20 minutes, then at 130° C. for 20 minutes in a microwave reactor. The reaction mixture was partitioned between aqueous Na2HCO3 solution (2.5%) and ethyl acetate. The aqueous phase was re-extracted with ethyl acetate and the combined organic layers were washed with brine, dried (Na2SO4), passed sequentially through two PS-Thiol cartridges and concentrated to dryness. The residue was triturated with methanol and then ether affording ethyl 2-(3-cyano-6-(isoquinolin-3-ylamino)pyrazin-2-yloxy)acetate (37 mg, 0.107 mmol, 25%). LC-MS (2) Rt 2.89 min; m/z (ESI+) 350 (M+H).

후처리

  1. customwas degassed under a stream of nitrogen gas
  2. customthe mixture was degassed for a further 5 minutes
  3. waitat 130° C. for 20 minutes in a microwave reactor
  4. customThe reaction mixture was partitioned between aqueous Na2HCO3 solution (2.5%) and ethyl acetate
  5. extractionThe aqueous phase was re-extracted with ethyl acetate
  6. washthe combined organic layers were washed with brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated to dryness
  9. customThe residue was triturated with methanol

출처 및 근거

ORD 기록
ord-e1a47ca270f246b19bfce3d4d1e88faf
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08530468B2

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