1,4-Dimethyl-N-[1-(phenylsulfonyl)-6-(trimethylstannanyl)-1H-indazol-4-yl]-1H-pyrazole-3-carboxamide → N-[6-(6-Cyano-1H-indol-4-yl)-1H-indazol-4-yl]-1,4-dimethyl-1H-pyrazole-3-carboxamide

HRID 520649노트

반응식

HRID 520649 반응식
Br[C:2]1[CH:10]=[C:9]([C:11]#[N:12])[CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][N:6]2S(C1C=CC([N+]([O-])=O)=CC=1)(=O)=O.[CH3:25][N:26]1[CH:30]=[C:29]([CH3:31])[C:28]([C:32]([NH:34][C:35]2[CH:43]=[C:42]([Sn](C)(C)C)[CH:41]=[C:40]3[C:36]=2[CH:37]=[N:38][N:39]3S(C2C=CC=CC=2)(=O)=O)=[O:33])=[N:27]1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN(C=O)C>[C:11]([C:9]1[CH:8]=[C:7]2[C:3]([CH:4]=[CH:5][NH:6]2)=[C:2]([C:42]2[CH:41]=[C:40]3[C:36]([CH:37]=[N:38][NH:39]3)=[C:35]([NH:34][C:32]([C:28]3[C:29]([CH3:31])=[CH:30][N:26]([CH3:25])[N:27]=3)=[O:33])[CH:43]=2)[CH:10]=1)#[N:12]

참가 물질

5

반응물 2

HCID 583564471,4-Dimethyl-N-[1-(phenylsulfonyl)-6-(trimethylstannanyl)-1H-indazol-4-yl]-1H-pyrazole-3-carboxamideHCID 666922724-Bromo-1-[(4-nitrophenyl)sulfonyl]-1H-indole-6-carbonitrile

생성물 1

HCID 53233212N-[6-(6-Cyano-1H-indol-4-yl)-1H-indazol-4-yl]-1,4-dimethyl-1H-pyrazole-3-carboxamide

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 6228Dimethylformamide용매

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온도
120 °C

실험 절차

4-Bromo-1-[(4-nitrophenyl)sulfonyl]-1H-indole-6-carbonitrile (70 mg), 1,4-dimethyl-N-[1-(phenylsulfonyl)-6-(trimethylstannanyl)-1H-indazol-4-yl]-1H-pyrazole-3-carboxamide (51 mg) and Pd(PPh3)4 (22 mg) were weighed to a microwave vial and DMF (1 ml) was added. The reaction was heated at 120° C. for 1 h, then cooled and passed through a silica (1 g) cartridge, which had been pre-washed with methanol and washed through with methanol:DCM. The solvent was dried under nitrogen blowdown. The residue was purified using MDAP (method K but using an isocratic 50:50 solvent mix over 10 min). Purified fraction was dissolved in methanol (1 ml) and 2M NaOH (aq) (2 ml) was added and the reaction left at RT over the weekend. The reaction was neutralised using 2M HCl (aq) and dried under nitrogen blowdown. The residue was taken into water and extracted into ethyl acetate. The ethyl acetate was passed through a hydrophobic frit, then through an SAX cartridge pre-conditioned with ethyl acetate. The solvent was evaporated by nitrogen blow down to give title compound, 12 mg.

후처리

  1. additionwas added
  2. temperaturecooled
  3. washhad been pre-washed with methanol
  4. washwashed through with methanol
  5. customThe solvent was dried under nitrogen
  6. customThe residue was purified
  7. additionmix over 10 min)
  8. customPurified fraction
  9. dissolutionwas dissolved in methanol (1 ml)
  10. addition2M NaOH (aq) (2 ml) was added
  11. waitthe reaction left at RT over the weekend
  12. customdried under nitrogen
  13. extractionextracted into ethyl acetate
  14. customThe solvent was evaporated by nitrogen blow down

출처 및 근거

ORD 기록
ord-ddfb70eb47554b59934a953c87838a19
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09326987B2

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