N-(4-(1-(4-methoxybenzyl)-3-(4-(dimethylamino)piperidin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-3-(4-fluorophenyl)-2-oxo-3-aza-bicyclo[3.1.0]hexane-1-carboxamide → N-(4-(3-(4-(dimethylamino)piperidin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-3-(4-fluorophenyl)-2-oxo-3-aza-bicyclo[3.1.0]hexane-1-carboxamide

HRID 2241330Notes

Reaction equation

HRID 2241330 reaction equation
COC1C=CC(C[N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([NH:24][C:25]([C:27]56[CH2:32][CH:31]5[CH2:30][N:29]([C:33]5[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=5)[C:28]6=[O:40])=[O:26])=[CH:20][C:19]=4[F:41])=[C:11]3[C:10]([N:42]3[CH2:47][CH2:46][CH:45]([N:48]([CH3:50])[CH3:49])[CH2:44][CH2:43]3)=[N:9]2)=CC=1>C(O)(C(F)(F)F)=O>[CH3:49][N:48]([CH3:50])[CH:45]1[CH2:46][CH2:47][N:42]([C:10]2[C:11]3[C:12](=[N:13][CH:14]=[CH:15][C:16]=3[O:17][C:18]3[CH:23]=[CH:22][C:21]([NH:24][C:25]([C:27]45[CH2:32][CH:31]4[CH2:30][N:29]([C:33]4[CH:34]=[CH:35][C:36]([F:39])=[CH:37][CH:38]=4)[C:28]5=[O:40])=[O:26])=[CH:20][C:19]=3[F:41])[NH:8][N:9]=2)[CH2:43][CH2:44]1

Participants

3

Reactant 1

HCID 68512071N-(4-(1-(4-methoxybenzyl)-3-(4-(dimethylamino)piperidin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-3-(4-fluorophenyl)-2-oxo-3-aza-bicyclo[3.1.0]hexane-1-carboxamide

Product 1

HCID 59304344N-(4-(3-(4-(dimethylamino)piperidin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-3-(4-fluorophenyl)-2-oxo-3-aza-bicyclo[3.1.0]hexane-1-carboxamideYield 68.9%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of N-(4-(1-(4-methoxybenzyl)-3-(4-(dimethylamino)piperidin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-3-(4-fluorophenyl)-2-oxo-3-aza-bicyclo[3.1.0]hexane-1-carboxamide (30 mg, 0.042 mmol) was heated in TFA (2 mL) for 4 hours. Excess TFA was evaporated and the residue was purified on a SCX column (7N ammonia in MeOH) to afford the product (17 mg, 68% yield) as a yellow solid. LRMS (APCI pos) m/e 588.2 (M+1). 1H NMR (400 MHz, CDCl3) δ 10.50 (s, 1H), 9.80 (s, 1H), 8.30 (s, 1H), 7.78-7.90 (m, 1H), 7.40-7.60 (m, 2H), 7.00-7.40 (m, 4H), 6.10-6.20 (m, 1H), 4.00-4.20 (m, 4H), 3.70-3.80 (m, 1H), 2.80-3.00 (m, 4H), 2.40 (s, 6H), 1.20-2.10 (m, 5H).

Workup

  1. customExcess TFA was evaporated
  2. customthe residue was purified on a SCX column (7N ammonia in MeOH)

Sources & evidence

ORD record
ord-d31655a7a6f44403a0f618253dff6137
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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