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

HRID 537202Notes

Reaction equation

HRID 537202 reaction equation
[C:1]([NH:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:16]([OH:18])=O)[CH:14]=2)[CH:9]=[CH:8][N:7]=1)([CH3:4])([CH3:3])[CH3:2].Cl.[C:20]([N:24]1[CH:32]=[C:31]2[C:26]([C:27](=[O:38])[NH:28][C:29]3([CH2:37][CH2:36][NH:35][CH2:34][CH2:33]3)[CH2:30]2)=[N:25]1)([CH3:23])([CH3:22])[CH3:21].C(N(CC)CC)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>CN(C)C=O>[C:20]([N:24]1[CH:32]=[C:31]2[C:26]([C:27](=[O:38])[NH:28][C:29]3([CH2:37][CH2:36][N:35]([C:16]([C:13]4[CH:14]=[C:15]5[C:10]([CH:9]=[CH:8][N:7]=[C:6]5[NH:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[CH:11][CH:12]=4)=[O:18])[CH2:34][CH2:33]3)[CH2:30]2)=[N:25]1)([CH3:23])([CH3:21])[CH3:22]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 674913562'-(tert-Butyl)-4',6'-dihydrospiro[piperidine-4,5'-pyrazolo[3,4-c]pyridin]-7'(2'H)-one hydrochlorideHCID 674915901-(Tert-butylamino)isoquinoline-7-carboxylic acid

Product 1

HCID 674916922'-(tert-butyl)-1-(1-(tert-butylamino)isoquinoline-7-carbonyl)-4',6'-dihydrospiro[piperidine-4,5'-pyrazolo[3,4-c]pyridin]-7'(2'H)-oneYield 24%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of 1-(tert-butylamino)isoquinoline-7-carboxylic acid (24.7 mg, 0.101 mmol) and 2′-tert-butyl-4′,6′-dihydrospiro[piperidine-4,5′-pyrazolo[3,4-c]pyridine]-7′(2′H)-one hydrochloride salt (33.9 mg, 0.101 mmol) in N,N-dimethylformamide (1 mL) was added triethylamine (0.07 mL, 0.50 mmol). The reaction mixture was stirred at room temperature for 10 minutes. Then 1-propanephosphonic acid cyclic anhydride (0.07 mL, 0.12 mmol, 50% solution in ethyl acetate) was added and the reaction mixture was stirred at room temperature overnight. N,N-dimethylformamide was removed under reduced pressure and the residue was purified by reversed-phase HPLC to give 2′-(tert-butyl)-1-(1-(tert-butylamino)isoquinoline-7-carbonyl)-4′,6′-dihydrospiro[piperidine-4,5′-pyrazolo[3,4-c]pyridin]-7′(2′H)-one (6.1 mg, 24%). +ESI (m+H) 489.3; HPLC retention time 2.94 minutes (Method B).

Workup

  1. stirringthe reaction mixture was stirred at room temperature overnight
  2. customN,N-dimethylformamide was removed under reduced pressure
  3. customthe residue was purified by reversed-phase HPLC

Sources & evidence

ORD record
ord-bd06aa20c1504957939585e731b07792
Source dataset
uspto-grants-2014_10
Patent number
US08859773B2

Reaction notes

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