Sodium Hydroxide → 6-(1H-Indol-4-yl)-4-[5-(1-piperazinylmethyl)-1,3-oxazol-2-yl]-1H-indazole

HRID 2042383ノート

反応式

HRID 2042383 の反応式
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](C(OC(C)(C)C)=O)[CH2:28][CH2:27]3)=[CH:23][N:24]=2)[CH:3]=1.CC1(C)C(C)(C)OB([C:47]2[CH:55]=[CH:54][CH:53]=[C:52]3[C:48]=2[CH:49]=[CH:50][NH:51]3)O1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[OH-].[Na+]>O1CCOCC1.O.Cl.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(Cl)Cl>[NH:51]1[C:52]2[C:48](=[C:47]([C:2]3[CH:10]=[C:9]4[C:5]([CH:6]=[N:7][NH:8]4)=[C:4]([C:20]4[O:21][C:22]([CH2:25][N:26]5[CH2:27][CH2:28][NH:29][CH2:30][CH2:31]5)=[CH:23][N:24]=4)[CH:3]=3)[CH:55]=[CH:54][CH:53]=2)[CH:49]=[CH:50]1

参加物

10

反応物 4

HCID 14798Sodium Hydroxide2 回HCID 62657Potassium Phosphate, TribasicHCID 113224711H-Indole-4-boronic acid, pinacol esterHCID 595647101,1-Dimethylethyl 4-({2-[6-chloro-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3-oxazol-5-yl}methyl)-1-piperazinecarboxylate

生成物 1

HCID 497840056-(1H-Indol-4-yl)-4-[5-(1-piperazinylmethyl)-1,3-oxazol-2-yl]-1H-indazole収率 19.9%

試薬・触媒・溶媒 5

HCID 178420574HCID 178420574、化合物触媒HCID 313Hydrochloric Acid溶媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 312751,4-Dioxane溶媒2 回

反応条件

温度
150 °C

実験手順

1,1-Dimethylethyl 4-({2-[6-chloro-1-(phenylsulfonyl)-1H-indazol-4-yl]-1,3-oxazol-5-yl}methyl)-1-piperazinecarboxylate (303 mg, 0.543 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (172 mg, 0.706 mmol, available from Frontier Scientific), 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) (30 mg, 0.054 mmol, available from Fluka) and tripotassium phosphate (346 mg, 1.629 mmol) were dissolved in 1,4-Dioxane (10 mL) and Water (2.5 mL). The reaction vessel was sealed and heated in Biotage Initiator microwave at 150° C. for 30 min. Aqueous 2M NaOH (5 ml) was then added and the mixture stirred for 2 hours. An additional portion of aqueous 2M NaOH (3 ml) was added and stirring continued until deprotection appeared complete by LCMS analysis. DCM was then added and the mixture was passed through a phase separator. The organic phase was collected. The aqueous phase was back extracted with DCM then the organic phases were combined and evaporated to give a brown oil. This was dissolved in 5 ml of 4M HCl in 1,4 dioxane and left stirring. The mixture was concentrated in vacuo and the resultant solid partitioned between DCM and 2M aqueous HCl. The aqueous phase was basified with 2M aqueous NaOH, then washed with DCM. The organic phase was concentrated in vacuo, then the residue dissolved in 2 ml DMSO/MeOH (1:1) and purified by MDAP (Method A). Combining appropriate fractions and concentrating by blow down under nitrogen at 40° C., afforded the title compound (43 mg).

後処理

  1. customThe reaction vessel was sealed
  2. stirringstirring
  3. customThe organic phase was collected
  4. extractionThe aqueous phase was back extracted with DCM
  5. customevaporated
  6. customto give a brown oil
  7. waitleft
  8. stirringstirring
  9. concentrationThe mixture was concentrated in vacuo
  10. customthe resultant solid partitioned between DCM and 2M aqueous HCl
  11. washwashed with DCM
  12. concentrationThe organic phase was concentrated in vacuo
  13. dissolutionthe residue dissolved in 2 ml DMSO/MeOH (1:1)
  14. custompurified by MDAP (Method A)
  15. concentrationconcentrating by blow down under nitrogen at 40° C.

出典と根拠

ORDレコード
ord-2312ccdbd2fa44ddb8dc238212799340
出典データセット
uspto-grants-2013_11
特許番号
US08586583B2

反応ノート

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