4-(4-Fluorophenyl)-3-oxo-3,4-dihydropyrazine-2-carboxylic acid → N-(3-fluoro-4-(3-(8-methyl-8-azabicyclo[3.2.1]octan-3-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-4-(4-fluorophenyl)-3-oxo-3,4-dihydropyrazine-2-carboxamide

HRID 2241441Notes

Reaction equation

HRID 2241441 reaction equation
[NH2:1][C:2]1[CH:36]=[CH:35][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[N:13](CC4C=CC(OC)=CC=4)[N:14]=[C:15]([NH:16][CH:17]4[CH2:23][CH:22]5[N:24]([CH3:25])[CH:19]([CH2:20][CH2:21]5)[CH2:18]4)[C:8]=23)=[C:4]([F:37])[CH:3]=1.[F:38][C:39]1[CH:44]=[CH:43][C:42]([N:45]2[CH:50]=[CH:49][N:48]=[C:47]([C:51]([OH:53])=O)[C:46]2=[O:54])=[CH:41][CH:40]=1>>[F:37][C:4]1[CH:3]=[C:2]([NH:1][C:51]([C:47]2[C:46](=[O:54])[N:45]([C:42]3[CH:41]=[CH:40][C:39]([F:38])=[CH:44][CH:43]=3)[CH:50]=[CH:49][N:48]=2)=[O:53])[CH:36]=[CH:35][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]2[NH:13][N:14]=[C:15]([NH:16][CH:17]3[CH2:23][CH:22]4[N:24]([CH3:25])[CH:19]([CH2:20][CH2:21]4)[CH2:18]3)[C:8]=12

Participants

3

Reactant 2

HCID 673494894-(4-Fluorophenyl)-3-oxo-3,4-dihydropyrazine-2-carboxylic acidHCID 685164114-(4-amino-2-fluorophenoxy)-1-(4-methoxybenzyl)-N-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine

Product 1

HCID 59304308N-(3-fluoro-4-(3-(8-methyl-8-azabicyclo[3.2.1]octan-3-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-4-(4-fluorophenyl)-3-oxo-3,4-dihydropyrazine-2-carboxamideYield 18%

Procedure

Prepared by a 2-step process from 4-(4-amino-2-fluorophenoxy)-1-(4-methoxybenzyl)-N-(8-methyl-8-azabicyclo[3.2.1]octan-3-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine (prepared as described in Example 101, Step A except using 8-methyl-8-azabicyclo[3.2.1]octan-3-amine) and 4-(4-fluorophenyl)-3-oxo-3,4-dihydropyrazine-2-carboxylic acid (Example 125, Step E) according to the procedure of Example 101, Step B. The crude was rinsed with Et2O to afford 7 mg (18%) of the desired product. The desired product was treated with 2N HCl (Et2O solution) in a solution of MeOH and EtOAc to afford HCl salt compound. LRMS (ESIpos) m/e 599.2 (M+1). 1H-NMR (400 MHz, CD3OD) δ 8.36 (m, 1H), 8.14 (d, 1H), 7.94 (m, 1H), 7.80 (m, 1H), 7.60 (m, 4H), 7.35 (t, 2H), 6.54 (d, 1H), 4.07 (m, 1H), 3.93 (m, 2H), 2.81 (s, 3H), 2.35-2.58 (m, 8H); 19F NMR (376 MHz, CD3OD) δ −113.5, −129.6.

Workup

  1. washThe crude was rinsed with Et2O

Sources & evidence

ORD record
ord-09bdbc19548b44a08c7b978ca98d44e4
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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