Water → N-[5-[4-(5-{[(2R,6S)-2,6-Dimethyl-4-morpholinyl]methyl}-1,3-oxazol-2-yl)-1-(phenylsulfonyl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]-2,4-difluorobenzenesulfonamide

HRID 520561ノート

反応式

HRID 520561 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][C@H:30]([CH3:32])[O:29][C@H:28]([CH3:33])[CH2:27]3)=[CH:23][N:24]=2)[CH:3]=1.[F:34][C:35]1[CH:40]=[C:39]([F:41])[CH:38]=[CH:37][C:36]=1[S:42]([NH:45][C:46]1[C:47]([O:61][CH3:62])=[N:48][CH:49]=[C:50](B2OC(C)(C)C(C)(C)O2)[CH:51]=1)(=[O:44])=[O:43].[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][C@H:28]1[O:29][C@@H:30]([CH3:32])[CH2:31][N:26]([CH2:25][C:22]2[O:21][C:20]([C:4]3[CH:3]=[C:2]([C:50]4[CH:51]=[C:46]([NH:45][S:42]([C:36]5[CH:37]=[CH:38][C:39]([F:41])=[CH:40][C:35]=5[F:34])(=[O:44])=[O:43])[C:47]([O:61][CH3:62])=[N:48][CH:49]=4)[CH:10]=[C:9]4[C:5]=3[CH:6]=[N:7][N:8]4[S:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)(=[O:13])=[O:12])=[N:24][CH:23]=2)[CH2:27]1

参加物

7

反応物 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 595647046-Chloro-4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-oxazol-2-yl)-1-(phenylsulfonyl)-1H-indazoleHCID 595647052,4-difluoro-N-(2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)benzenesulfonamide

生成物 1

HCID 59564711N-[5-[4-(5-{[(2R,6S)-2,6-Dimethyl-4-morpholinyl]methyl}-1,3-oxazol-2-yl)-1-(phenylsulfonyl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]-2,4-difluorobenzenesulfonamide収率 34%

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-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3-oxazol-2-yl)-1-(phenylsulfonyl)-1H-indazole (0.2 g, 0.411 mmol) and 2,4-difluoro-N-[2-(methoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinyl]benzenesulfonamide (0.228 mg, 0.534 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 (11.5 mg, 0.021 mmol), potassium phosphate tribasic (0.262 g, 1.23 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 and the residue partitioned between dichloromethane (5 ml) and water (5 ml). The layers were separated and the aqueous extracted with further dichloromethane (2×2.5 ml). The combined organics were concentrated under a stream of nitrogen and the residue dissolved in DMSO and a few drops of dichloromethane (3 ml) and purified by MDAP (method H) in 3 injections. The appropriate fractions were evaporated in vacuo to give the title compound as a pale brown solid (0.105 g).

後処理

  1. filtrationfiltered through a silica SPE
  2. washeluting with methanol
  3. customThe solvent was removed
  4. customthe residue partitioned between dichloromethane (5 ml) and water (5 ml)
  5. customThe layers were separated
  6. extractionthe aqueous extracted with further dichloromethane (2×2.5 ml)
  7. concentrationThe combined organics were concentrated under a stream of nitrogen
  8. dissolutionthe residue dissolved in DMSO
  9. customa few drops of dichloromethane (3 ml) and purified by MDAP (method H) in 3 injections
  10. customThe appropriate fractions were evaporated in vacuo

出典と根拠

ORDレコード
ord-9c551237ff4b4a20bea3b0f194ed06e3
出典データセット
uspto-grants-2016_05
特許番号
US09326987B2

反応ノート

読み込み中…