Water → N-(2-(Methyloxy)-5-{1-(phenylsulfonyl)-4-[5-(tetrahydro-1,4-oxazepin-4(5H)-ylmethyl)-1,3,4-oxadiazol-2-yl]-1H-indazol-6-yl}-3-pyridinyl)methanesulfonamide

HRID 38846

반응식

HRID 38846 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[CH2:32][CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)=[N:23][N:24]=2)[CH:3]=1.[CH3:33][O:34][C:35]1[C:40]([NH:41][S:42]([CH3:45])(=[O:44])=[O:43])=[CH:39][C:38](B2OC(C)(C)C(C)(C)O2)=[CH:37][N:36]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O>O1CCOCC1.[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]>[CH3:33][O:34][C:35]1[C:40]([NH:41][S:42]([CH3:45])(=[O:44])=[O:43])=[CH:39][C:38]([C:2]2[CH:10]=[C:9]3[C:5]([CH:6]=[N:7][N:8]3[S:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)(=[O:13])=[O:12])=[C:4]([C:20]3[O:21][C:22]([CH2:25][N:26]4[CH2:32][CH2:31][CH2:30][O:29][CH2:28][CH2:27]4)=[N:23][N:24]=3)[CH:3]=2)=[CH:37][N:36]=1

참가 물질

7

반응물 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 59564698N-(2-Methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methanesulfonamideHCID 667768846-Bromo-1-(phenylsulfonyl)-4-[5-(tetrahydro-1,4-oxazepin-4(5H)-ylmethyl)-1,3,4-oxadiazol-2-yl]-1H-indazole

생성물 1

HCID 66691651N-(2-(Methyloxy)-5-{1-(phenylsulfonyl)-4-[5-(tetrahydro-1,4-oxazepin-4(5H)-ylmethyl)-1,3,4-oxadiazol-2-yl]-1H-indazol-6-yl}-3-pyridinyl)methanesulfonamide

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

6-Bromo-1-(phenylsulfonyl)-4-[5-(tetrahydro-1,4-oxazepin-4(5H)-ylmethyl)-1,3,4-oxadiazol-2-yl]-1H-indazole (279 mg, 0.538 mmol) was dissolved in 1,4-dioxane (5 ml) and half of the resulting solution was charged to a reaction vessel. N-[2-(methyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinyl]methanesulfonamide (114 mg, 0.347 mmol), 1,1′-bis(diphenylphosphino)ferrocene palladium dichloride (39.5 mg, 0.054 mmol), potassium phosphate tribasic (171.5 mg, 0.808 mmol) and water (0.25 ml) were added. The reaction mixture was heated 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 purified by preparative HPLC using the following method:

후처리

  1. additionhalf of the resulting solution was charged to a reaction vessel
  2. washwashing with MeOH
  3. customThe solvent was removed under a stream of nitrogen
  4. customthe residue was partitioned between DCM (10 ml) and water (10 ml)
  5. customseparated with a hydrophobic frit
  6. customthe solvent again removed under a stream of nitrogen
  7. customThe residue was purified by preparative HPLC

출처 및 근거

ORD 기록
ord-e198f219fc5d43b68a8aa92ccefe333d
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08524751B2

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