Sodium Iodide → 6-bromo-4-{5-[(8aS)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylmethyl]-1,3,4-oxadiazol-2-yl}-1-(phenylsulfonyl)-1H-indazole

HRID 38849

반응식

HRID 38849 반응식
[Br:1][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]Cl)=[N:23][N:24]=2)[CH:3]=1.[I-].[Na+].[N:29]12[CH2:37][CH2:36][CH2:35][C@H:34]1[CH2:33][NH:32][CH2:31][CH2:30]2.CCN(C(C)C)C(C)C>C(#N)C.C(Cl)Cl>[Br:1][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:32]3[CH2:31][CH2:30][N:29]4[CH2:37][CH2:36][CH2:35][C@H:34]4[CH2:33]3)=[N:23][N:24]=2)[CH:3]=1

참가 물질

7

반응물 4

HCID 5238Sodium IodideHCID 81531DiisopropylethylamineHCID 781249(6S)-1,4-Diazabicyclo(4.3.0)nonaneHCID 666956686-bromo-4-[5-(chloromethyl)-1,3,4-oxadiazol-2-yl]-1-(phenylsulfonyl)-1H-indazole

생성물 1

HCID 666958546-bromo-4-{5-[(8aS)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylmethyl]-1,3,4-oxadiazol-2-yl}-1-(phenylsulfonyl)-1H-indazole수율 61.2%

시약·촉매·용매 2

HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매2회

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온도
70 °C

실험 절차

6-Bromo-4-[5-(chloromethyl)-1,3,4-oxadiazol-2-yl]-1-(phenylsulfonyl)-1H-indazole (300 mg, 0.661 mmol) and sodium iodide (99 mg, 0.661 mmol) were weighed into a round-bottomed flask and dissolved in acetonitrile (2 ml) before (S)-1,4-diazabicyclo[4.3.0]nonane (167 mg, 1.322 mmol, available from ABCR GmbH & CO.KG) and DIPEA (0.231 ml, 1.322 mmol) were added. The mixture was heated to 70° C. for 2 h. The mixture was cooled, diluted with DCM and washed with 2 M aqueous HCl (2 ml). The organic layer was separated by hydrophobic frit. The aqueous extracts were combined and neutralised to pH 7 with NaOH then extracted with more DCM (2×10 ml) which was combined with the other organic extracts and evaporated under a stream of nitrogen to give an orange oil. This was dissolved in DCM and loaded onto the top of a 10 g silica cartridge that was subsequently eluted with 0-15% MeOH(+1% triethylamine)/DCM over 15 mins. The appropriate fractions were combined and the solvent removed in vacuo to give the title compound as a cream solid (220 mg).

후처리

  1. additionwere added
  2. temperatureThe mixture was cooled
  3. washwashed with 2 M aqueous HCl (2 ml)
  4. customThe organic layer was separated by hydrophobic frit
  5. extractionthen extracted with more DCM (2×10 ml) which
  6. customevaporated under a stream of nitrogen
  7. customto give an orange oil
  8. washwas subsequently eluted with 0-15% MeOH(+1% triethylamine)/DCM over 15 mins
  9. customthe solvent removed in vacuo

출처 및 근거

ORD 기록
ord-ed3410ad0501475e838a07c4af6e2d0b
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08524751B2

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