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

HRID 2036066노트

반응식

HRID 2036066 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](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

참가 물질

10

반응물 4

HCID 14798Sodium Hydroxide2회HCID 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

생성물 1

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

시약·촉매·용매 5

HCID 178420574HCID 178420574, 화합물촉매HCID 313Hydrochloric Acid용매HCID 962Water용매HCID 6344Dichloromethane용매HCID 312751,4-Dioxane용매2회

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온도
150 °C

실험 절차

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 acqueous HCl. The aqueous phase was basified with 2M aquous 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).

후처리

  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 acqueous 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.

출처 및 근거

ORD 기록
ord-f2b646c4f1e94f0c84f30da89903ee7a
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08575162B2

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