Potassium Phosphate, Tribasic → N-[5-[4-{5-[(8aS)-Hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylmethyl]-1,3,4-oxadiazol-2-yl}-1-(phenylsulfonyl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]methanesulfonamide

HRID 38848

반응식

HRID 38848 반응식
Br[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]4[CH2:32][CH2:33][CH2:34][C@H:28]4[CH2:27]3)=[N:23][N:24]=2)[CH:3]=1.[CH3:35][O:36][C:37]1[C:42]([NH:43][S:44]([CH3:47])(=[O:46])=[O:45])=[CH:41][C:40](B2OC(C)(C)C(C)(C)O2)=[CH:39][N:38]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH2:27]1[N:26]([CH2:25][C:22]2[O:21][C:20]([C:4]3[CH:3]=[C:2]([C:40]4[CH:41]=[C:42]([NH:43][S:44]([CH3:47])(=[O:45])=[O:46])[C:37]([O:36][CH3:35])=[N:38][CH:39]=4)[CH:10]=[C:9]4[C:5]=3[CH:6]=[N:7][N:8]4[S:11]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)(=[O:12])=[O:13])=[N:24][N:23]=2)[CH2:31][CH2:30][N:29]2[CH2:32][CH2:33][CH2:34][C@@H:28]12

참가 물질

5

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 59564698N-(2-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methanesulfonamideHCID 666958546-bromo-4-{5-[(8aS)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylmethyl]-1,3,4-oxadiazol-2-yl}-1-(phenylsulfonyl)-1H-indazole

생성물 1

HCID 66693044N-[5-[4-{5-[(8aS)-Hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylmethyl]-1,3,4-oxadiazol-2-yl}-1-(phenylsulfonyl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]methanesulfonamide수율 77.7%

시약·촉매·용매 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매

반응 조건

온도
100 °C

실험 절차

To a solution of 6-bromo-4-{5-[(8aS)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylmethyl]-1,3,4-oxadiazol-2-yl}-1-(phenylsulfonyl)-1H-indazole (100 mg, 0.184 mmol) was added N-[2-(methyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinyl]methanesulfonamide (72.5 mg, 0.221 mmol), 1,1′-bis(diphenylphosphino)ferrocene palladium dichloride (36 mg, 0.049 mmol) and potassium phosphate tribasic (126 mg, 0.594 mmol). The mixture was heated under microwave irradiation at 100° C. for 20 mins. The mixture was passed through a 1 g silica SPE cartridge, washing with MeOH. The solvent was removed under a stream of nitrogen and the residue was partitioned between DCM (10 ml) and water (10 ml), separated with a hydrophobic frit and the solvent again removed under a stream of nitrogen. The residue was dissolved in DCM and added to the top of a 10 g silica SPE cartridge that was subsequently eluted with 0-15% MeOH/DCM over 20 mins. The product-containing fractions were combined and the solvent removed in vacuo to give the title compound as an orange oil (95 mg).

후처리

  1. washwashing with MeOH
  2. customThe solvent was removed under a stream of nitrogen
  3. customthe residue was partitioned between DCM (10 ml) and water (10 ml)
  4. customseparated with a hydrophobic frit
  5. customthe solvent again removed under a stream of nitrogen
  6. dissolutionThe residue was dissolved in DCM
  7. additionadded to the top of a 10 g silica SPE cartridge that
  8. washwas subsequently eluted with 0-15% MeOH/DCM over 20 mins
  9. customthe solvent removed in vacuo

출처 및 근거

ORD 기록
ord-88926e98ff5b41278e3c6b59ec958b79
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08524751B2

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