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Potassium Phosphate, Tribasic → N-(5-(2,6-difluorobenzyl)-1-methylpiperidin-3-yl)-3-(2-methylpyridin-4-yl)-1-trityl-1H-indazole-5-carboxamide

HRID 1467340
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HRID 1467340 반응식
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]([NH:13][CH:14]3[CH2:19][CH:18]([CH2:20][C:21]4[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=4[F:28])[CH2:17][N:16]([CH3:29])[CH2:15]3)=[O:12])[CH:9]=2)[N:4]([C:30]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[N:3]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH3:57][C:58]1[CH:63]=[C:62](B2OC(C)(C)C(C)(C)O2)[CH:61]=[CH:60][N:59]=1>Cl[Pd]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]>[F:27][C:26]1[CH:25]=[CH:24][CH:23]=[C:22]([F:28])[C:21]=1[CH2:20][CH:18]1[CH2:17][N:16]([CH3:29])[CH2:15][CH:14]([NH:13][C:11]([C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[N:4]([C:30]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)([C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)[C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)[N:3]=[C:2]3[C:62]2[CH:61]=[CH:60][N:59]=[C:58]([CH3:57])[CH:63]=2)=[O:12])[CH2:19]1
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참가 물질

5

반응물 3

HCID 62657Potassium Phosphate, TribasicHCID 164142742-Methylpyridine-4-boronic acid pinacol esterHCID 679965083-bromo-N-(5-(2,6-difluorobenzyl)-1-methylpiperidin-3-yl)-1-trityl-1H-indazole-5-carboxamide

생성물 1

HCID 70653003N-(5-(2,6-difluorobenzyl)-1-methylpiperidin-3-yl)-3-(2-methylpyridin-4-yl)-1-trityl-1H-indazole-5-carboxamide

시약·촉매·용매 1

HCID 44119782
Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)
촉매

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온도
80 °C

실험 절차

3-bromo-N-(5-(2,6-difluorobenzyl)-1-methylpiperidin-3-yl)-1-trityl-1H-indazole-5-carboxamide (0.050 g, 0.0716 mmol), [1,1′-Bis(diphenylphosphino)ferrocene]-dichloropalladium(II) (0.0052 g, 0.00716 mmol), Potassium phosphate tribasic (0.046 g, 0.215 mmol) and 2-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.018 g, 0.0788 mmol) was added into a flask. After purging the reaction vessel with nitrogen gas, dioxane (0.215 mL) and water (0.043 mL) was added. The reaction was allowed to stir at 80° C. for 16 hrs. The reaction was quenched with water (1 mL) and extracted with dichloromethane (3×1 mL). The extracts were combined, dried using sodium sulfate, filtered through celite, and concentrated under vacuo. The crude product was progressed to the next step without further purification. LC-MS found 718.2, calcd M+H 718.3.

후처리

  1. customAfter purging the reaction vessel with nitrogen gas, dioxane (0.215 mL) and water (0.043 mL)
  2. additionwas added
  3. customThe reaction was quenched with water (1 mL)
  4. extractionextracted with dichloromethane (3×1 mL)
  5. customdried
  6. filtrationfiltered through celite
  7. concentrationconcentrated under vacuo
  8. customThe crude product was progressed to the next step without further purification

출처 및 근거

ORD 기록
ord-a22383aa91e64f4583b726ecf591ef8f
출처 데이터셋
uspto-grants-2015_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08999957B2

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