Water → N-[5-[4-(5-{[4-(1-Methylethyl)-1-piperazinyl]methyl}-1,3-oxazol-2-yl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]methanesulfonamide

HRID 2036061

반응식

HRID 2036061 반응식
Cl[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2S(C2C=CC=CC=2)(=O)=O)=[C:4]([C:20]2[O:21][C:22]([CH2:25][N:26]3[CH2:31][CH2:30][N:29]([CH:32]([CH3:34])[CH3:33])[CH2:28][CH2:27]3)=[CH:23][N:24]=2)[CH:3]=1.[CH3:35][O:36][C:37]1[C:42]([NH:43][S:44]([CH3:47])(=[O:46])=[O:45])=[CH:41][C:40](B2OC(C)(C)C(C)(C)O2)=[CH:39][N:38]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O>O1CCOCC1.Cl[Pd]C1C=CC=CC=1C1C=CC=CC=1N(C)C.[C@H]12C[C@H](CC1)CC2PC1C[C@H]2C[C@@H]1CC2>[CH3:33][CH:32]([N:29]1[CH2:28][CH2:27][N:26]([CH2:25][C:22]2[O:21][C:20]([C:4]3[CH:3]=[C:2]([C:40]4[CH:41]=[C:42]([NH:43][S:44]([CH3:47])(=[O:45])=[O:46])[C:37]([O:36][CH3:35])=[N:38][CH:39]=4)[CH:10]=[C:9]4[C:5]=3[CH:6]=[N:7][NH:8]4)=[N:24][CH:23]=2)[CH2:31][CH2:30]1)[CH3:34]

참가 물질

7

반응물 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 59564698N-(2-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methanesulfonamideHCID 595647082-[1-(Benzenesulfonyl)-6-chloroindazol-4-yl]-5-[(4-propan-2-ylpiperazin-1-yl)methyl]-1,3-oxazole

생성물 1

HCID 49783924N-[5-[4-(5-{[4-(1-Methylethyl)-1-piperazinyl]methyl}-1,3-oxazol-2-yl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]methanesulfonamide수율 10.5%

시약·촉매·용매 2

HCID 178420574HCID 178420574, 화합물촉매HCID 312751,4-Dioxane용매

반응 조건

온도
120 °C

실험 절차

To a solution of 6-chloro-4-(5-{[4-(1-methylethyl)-1-piperazinyl]methyl}-1,3-oxazol-2-yl)-1-(phenylsulfonyl)-1H-indazole (200 mg, 0.400 mmol) and N-[2-(methoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridyl]methanesulfonamide (171 mg, 0.520 mmol) in 1,4-dioxane (2 ml) was added chloro[2′-(dimethylamino)-2-biphenylyl]palladium-1(1R,4S)-bicyclo[2.2.1]hept-2-yl[(1S,4R)-bicyclo[2.2.1]hept-2-yl]phosphane (11.2 mg, 0.020 mmol), potassium phosphate tribasic (255 mg, 1.20 mmol) and water (0.2 ml). The reaction mixture was heated and stirred at 120° C. under microwave irradiation for 3 h. The reaction mixture was filtered through a silica SPE and eluted with methanol. The solvent was removed in vacuo and the residue partitioned between dichloromethane (5 ml) and water (5 ml). The layers were separated and the aqueous extracted with further dichloromethane (2×2 ml). The combined organics were concentrated under a stream of nitrogen and the residue dissolved in MeOH:DMSO (2 ml, 1:1, v/v) and purified by MDAP (method A) in 2 injections. The appropriate fractions were combined and concentrated and the residue dissolved in MeOH:DMSO (1 ml, 1:1, v/v) and further purified by MDAP (method B). The appropriate fractions were basified to pH 7 with saturated sodium bicarbonate solution and extracted with dichloromethane (2×20 ml). The combined organics were dried (hydrophobic frit) and concentrated to give the title compound as a white solid (22 mg).

후처리

  1. temperatureThe reaction mixture was heated
  2. filtrationThe reaction mixture was filtered through a silica SPE
  3. washeluted with methanol
  4. customThe solvent was removed in vacuo
  5. customthe residue partitioned between dichloromethane (5 ml) and water (5 ml)
  6. customThe layers were separated
  7. extractionthe aqueous extracted with further dichloromethane (2×2 ml)
  8. concentrationThe combined organics were concentrated under a stream of nitrogen
  9. dissolutionthe residue dissolved in MeOH
  10. customDMSO (2 ml, 1:1, v/v) and purified by MDAP (method A) in 2 injections
  11. concentrationconcentrated
  12. dissolutionthe residue dissolved in MeOH
  13. customDMSO (1 ml, 1:1, v/v) and further purified by MDAP (method B)
  14. extractionextracted with dichloromethane (2×20 ml)
  15. customThe combined organics were dried (hydrophobic frit)
  16. concentrationconcentrated

출처 및 근거

ORD 기록
ord-bc75891cff4046829dfb8f509ff8a35d
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08575162B2

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