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

HRID 520562

反応式

HRID 520562 の反応式
Cl[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)(=[O:13])=[O:12])=[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.[F:35][C:36]1[CH:41]=[C:40]([F:42])[CH:39]=[CH:38][C:37]=1[S:43]([NH:46][C:47]1[C:48]([O:62][CH3:63])=[N:49][CH:50]=[C:51](B2OC(C)(C)C(C)(C)O2)[CH:52]=1)(=[O:45])=[O:44].[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>[F:35][C:36]1[CH:41]=[C:40]([F:42])[CH:39]=[CH:38][C:37]=1[S:43]([NH:46][C:47]1[C:48]([O:62][CH3:63])=[N:49][CH:50]=[C:51]([C:2]2[CH:10]=[C:9]3[C:5]([CH:6]=[N:7][N:8]3[S:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)(=[O:12])=[O:13])=[C:4]([C:20]3[O:21][C:22]([CH2:25][N:26]4[CH2:27][CH2:28][N:29]([CH:32]([CH3:33])[CH3:34])[CH2:30][CH2:31]4)=[CH:23][N:24]=3)[CH:3]=2)[CH:52]=1)(=[O:45])=[O:44]

参加物

7

反応物 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 595647052,4-difluoro-N-(2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)benzenesulfonamideHCID 595647082-[1-(Benzenesulfonyl)-6-chloroindazol-4-yl]-5-[(4-propan-2-ylpiperazin-1-yl)methyl]-1,3-oxazole

生成物 1

HCID 595647092,4-Difluoro-N-[5-[4-(5-{[4-(1-methylethyl)-1-piperazinyl]methyl}-1,3-oxazol-2-yl)-1-(phenylsulfonyl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]benzenesulfonamide収率 26.5%

試薬・触媒・溶媒 2

HCID 178420574HCID 178420574、化合物触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

To a solution of 6-chloro-4-(5-{[4-(1-methylethyl)-1-piperazinyl]methyl}-1,3-oxazol-2-yl)-1-(phenylsulfonyl)-1H-indazole (0.2 g, 0.40 mmol) and 2,4-difluoro-N-[2-(methoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinyl]benzenesulfonamide (0.222 g, 0.52 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 g, 0.020 mmol), potassium phosphate tribasic (0.255 g, 1.20 mmol) and water (0.2 ml). The reaction mixture was heated to 120° C. with stirring for 3 h under microwave irradiation then filtered through a silica SPE, eluting 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 purified using silica gel chromatography, eluting with 0-25% methanol in dichloromethane. The appropriate fractions were evaporated in vacuo to give the title compound as a brown solid (0.081 g).

後処理

  1. filtrationthen filtered through a silica SPE
  2. washeluting with methanol
  3. customThe solvent was removed in vacuo
  4. customthe residue partitioned between dichloromethane (5 ml) and water (5 ml)
  5. customThe layers were separated
  6. extractionthe aqueous extracted with further dichloromethane (2×2 ml)
  7. concentrationThe combined organics were concentrated under a stream of nitrogen
  8. customthe residue purified
  9. washeluting with 0-25% methanol in dichloromethane
  10. customThe appropriate fractions were evaporated in vacuo

出典と根拠

ORDレコード
ord-2081b06ed8ae4b2f8ab2d7156ac9cb37
出典データセット
uspto-grants-2016_05
特許番号
US09326987B2

関連ノート

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