Dichloromethane → 2'-tert-butyl-1-(3-methoxyisoquinoline-6-carbonyl)-4',6'-dihydrospiro[piperidine-4,5'-pyrazolo[3,4-c]pyridin]-7'(2'H)-one

HRID 537197Notes

Reaction equation

HRID 537197 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][C:6]([O:12][CH3:13])=[CH:5]2.Cl.[C:15]([N:19]1[CH:27]=[C:26]2[C:21]([C:22](=[O:33])[NH:23][C:24]3([CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)[CH2:25]2)=[N:20]1)([CH3:18])([CH3:17])[CH3:16].[C:34]([O-])(=[O:36])C.[Na+].ClCCl>O1CCOCC1.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]>[C:15]([N:19]1[CH:27]=[C:26]2[C:21]([C:22](=[O:33])[NH:23][C:24]3([CH2:32][CH2:31][N:30]([C:34]([C:2]4[CH:3]=[C:4]5[C:9](=[CH:10][CH:11]=4)[CH:8]=[N:7][C:6]([O:12][CH3:13])=[CH:5]5)=[O:36])[CH2:29][CH2:28]3)[CH2:25]2)=[N:20]1)([CH3:18])([CH3:16])[CH3:17]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 517045Sodium AcetateHCID 674913562'-(tert-Butyl)-4',6'-dihydrospiro[piperidine-4,5'-pyrazolo[3,4-c]pyridin]-7'(2'H)-one hydrochloride2×HCID 674918076-Bromo-3-methoxyisoquinoline2×

Product 1

HCID 674915822'-tert-butyl-1-(3-methoxyisoquinoline-6-carbonyl)-4',6'-dihydrospiro[piperidine-4,5'-pyrazolo[3,4-c]pyridin]-7'(2'H)-one

Reagents, catalysts & solvents 2

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

Conditions

Temperature
80 °C

Procedure

To a solution of 6-bromo-3-methoxyisoquinoline (Intermediate 43, 89.9 mg, 0.378 mmol) in 1,4-dioxane (6 mL) was added 2′-tert-butyl-4′,6′-dihydrospiro[piperidine-4,5′-pyrazolo[3,4-c]pyridin]-7′(2′H)-one hydrochloride salt (Intermediate 4, 244 mg, 0.727 mmol) and sodium acetate (130 mg, 1.5 mmol). Nitrogen gas was bubbled through the mixture for 15 minutes. Then added [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II), complex with dichloromethane (102 mg, 0.125 mmol), capped the reaction vessel and bubbled through carbon monoxide gas for 5 minutes. The reaction was then heated to 80° C. for 18 hours. The reaction was cooled to room temperature and diluted with ethyl acetate. The mixture was filtered through Celite and the filtrate was concentrated. Purification by reversed-phase HPLC gave the title compound. +ESI (M+H) 448.1; HPLC retention time 2.26 minutes (Method A).

Workup

  1. customNitrogen gas was bubbled through the mixture for 15 minutes
  2. custombubbled through carbon monoxide gas for 5 minutes
  3. temperatureThe reaction was cooled to room temperature
  4. additiondiluted with ethyl acetate
  5. filtrationThe mixture was filtered through Celite
  6. concentrationthe filtrate was concentrated
  7. customPurification by reversed-phase HPLC

Sources & evidence

ORD record
ord-e6dc0164a6ff4577948e3577c55080c8
Source dataset
uspto-grants-2014_10
Patent number
US08859773B2

Reaction notes

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