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

HRID 1467340Notes

Reaction equation

HRID 1467340 reaction equation
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

Participants

5

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

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

Conditions

Temperature
80 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-a22383aa91e64f4583b726ecf591ef8f
Source dataset
uspto-grants-2015_04
Patent number
US08999957B2

Reaction notes

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