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Acetonitrile → N-[6-(6-Cyano-1H-indol-4-yl)-1H-indazol-4-yl]-1-(1-methylethyl)-1H-pyrazole-5-carboxamide

HRID 244738
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HRID 244738 반응식
[CH3:1][CH:2]([N:4]1[C:8]([C:9]([NH:11][C:12]2[C:13]3[C:17]([CH:18]=[C:19](B4OC(C)(C)CC(C)(C)O4)[CH:20]=2)=[N:16][N:15](C2CCCCO2)[CH:14]=3)=[O:10])=[CH:7][CH:6]=[N:5]1)[CH3:3].Br[C:38]1[CH:46]=[C:45]([C:47]#[N:48])[CH:44]=[C:43]2[C:39]=1[CH:40]=[CH:41][NH:42]2.[O-]P(OP(OP([O-])([O-])=O)([O-])=O)(=O)[O-].[K+].[K+].[K+].[K+].[K+].CC#N>O1CCOCC1.O.Cl[Pd]C1C=CC=CC=1C1C=CC=CC=1N(C)C.[C@H]12C[C@H](CC1)CC2PC1C[C@H]2C[C@@H]1CC2>[C:47]([C:45]1[CH:44]=[C:43]2[C:39]([CH:40]=[CH:41][NH:42]2)=[C:38]([C:19]2[CH:18]=[C:17]3[C:13]([CH:14]=[N:15][NH:16]3)=[C:12]([NH:11][C:9]([C:8]3[N:4]([CH:2]([CH3:3])[CH3:1])[N:5]=[CH:6][CH:7]=3)=[O:10])[CH:20]=2)[CH:46]=1)#[N:48]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

8

반응물 4

HCID 6342AcetonitrileHCID 61695Pentapotassium TriphosphateHCID 247288834-bromo-1H-indole-6-carbonitrileHCID 582557371-(1-Methylethyl)-N-[2-(tetrahydro-2H-pyran-2-yl)-6-(4,4,6,6-tetramethyl-1,3,2-dioxaborinan-2-yl)-2H-indazol-4-yl]-1H-pyrazole-5-carboxamide

생성물 1

HCID 58356342N-[6-(6-Cyano-1H-indol-4-yl)-1H-indazol-4-yl]-1-(1-methylethyl)-1H-pyrazole-5-carboxamide
수율 15.6%

시약·촉매·용매 3

HCID 178420574HCID 178420574, 화합물촉매HCID 962Water용매HCID 312751,4-Dioxane용매2회

실험 절차

1-(1-Methylethyl)-N-[2-(tetrahydro-2H-pyran-2-yl)-6-(4,4,6,6-tetramethyl-1,3,2-dioxaborinan-2-yl)-2H-indazol-4-yl]-1H-pyrazole-5-carboxamide (49 mg, 0.1 mmol) was dissolved in 1,4-Dioxane (0.4 mL) and added to 4-bromo-1H-indole-6-carbonitrile (22 mg, 0.1 mmol, available from Sinova) in a microwave vessel. 1,4-Dioxane (0.4 ml) was added followed by chloro[2′-(dimethylamino)-2-biphenylyl]palladium-(1R,4S)-bicyclo[2.2.1]hept-2-yl[(1S,4R)-bicyclo[2.2.1]hept-2-yl]phosphane (1:1) (Solvias catalyst, 2 mg, 0.004 mmol, (heaped microspatula) available from ABCR) and a solution of potassium triphosphate (0.2 g, 0.1 mmol) in water (0.2 ml). The vessel was sealed and heated in CEM Discover using initial 150 W to 110° C. for 20 min. After cooling the solution was loaded onto a C18 SPE cartridge (pre-conditioned with MeCN/0.1% TFA) and flushed through with a further 3 ml MeCN/0.1% TFA. Solvent was removed by blowdown under a stream of nitrogen. The residue was dissolved in MeOH (0.5 ml) and loaded onto a SCX-2 SPE cartridge (1 g) pre-conditioned with MeOH. The material was left on the column for 1 hr then eluted with 2M ammonia/MeOH and evaporated to dryness. The sample was purified by Mass Directed AutoPrep (Method C) to afford the title compound (6.4 mg).

후처리

  1. customThe vessel was sealed
  2. temperatureheated in CEM Discover
  3. customfor 20 min
  4. temperatureAfter cooling the solution
  5. customflushed through with a further 3 ml MeCN/0.1% TFA
  6. customSolvent was removed by blowdown under a stream of nitrogen
  7. dissolutionThe residue was dissolved in MeOH (0.5 ml)
  8. washthen eluted with 2M ammonia/MeOH
  9. customevaporated to dryness
  10. customThe sample was purified by Mass Directed AutoPrep (Method C)

출처 및 근거

ORD 기록
ord-dd4ba67a312d488ab9a35a6075471e98
출처 데이터셋
uspto-grants-2014_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08658635B2

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