N-(4-(1-(4-methoxybenzyl)-3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-1-(4-fluorophenyl)-2-oxoazepane-3-carboxamide → N-(3-fluoro-4-(3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-1-(4-fluorophenyl)-2-oxoazepane-3-carboxamide

HRID 2241381Notes

Reaction equation

HRID 2241381 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]([CH:27]5[CH2:33][CH2:32][CH2:31][CH2:30][N:29]([C:34]6[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=6)[C:28]5=[O:41])=[O:26])=[CH:20][C:19]=4[F:42])=[C:11]3[C:10]([NH:43][CH:44]3[CH2:49][CH2:48][N:47]([CH3:50])[CH2:46][CH2:45]3)=[N:9]2)=CC=1>C(O)(C(F)(F)F)=O>[F:42][C:19]1[CH:20]=[C:21]([NH:24][C:25]([CH:27]2[CH2:33][CH2:32][CH2:31][CH2:30][N:29]([C:34]3[CH:35]=[CH:36][C:37]([F:40])=[CH:38][CH:39]=3)[C:28]2=[O:41])=[O:26])[CH:22]=[CH:23][C:18]=1[O:17][C:16]1[CH:15]=[CH:14][N:13]=[C:12]2[NH:8][N:9]=[C:10]([NH:43][CH:44]3[CH2:49][CH2:48][N:47]([CH3:50])[CH2:46][CH2:45]3)[C:11]=12

Participants

3

Reactant 1

HCID 68512277N-(4-(1-(4-methoxybenzyl)-3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-1-(4-fluorophenyl)-2-oxoazepane-3-carboxamide

Product 1

HCID 59304319N-(3-fluoro-4-(3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-1-(4-fluorophenyl)-2-oxoazepane-3-carboxamideYield 30.3%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of N-(4-(1-(4-methoxybenzyl)-3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-1-(4-fluorophenyl)-2-oxoazepane-3-carboxamide (20 mg, 0.028 mmol) was heated in TFA (1 mL) at 55° C. for 3 hours. TFA was evaporated and EtOAc was added to dilute the mixture. The mixture washed with saturated aqueous NaHCO3, brine, dry with Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography (20% MeOH in CH2Cl2) to afford the product (5 mg, 30% yield) as a white solid. LRMS (APCI pos) m/e 590.1 (M+1). 1H NMR (400 MHz, DMSO-d6): δ 12.15 (s, 1H), 10.20 (s, 1H), 8.10 (s, 1H), 7.82 (d, 1H), 7.18-7.50 (m, 7H), 5.98-6.00 (m, 1H), 5.10-5.20 (m, 1H), 3.90-4.02 (m, 2H), 3.40-3.62 (m, 2H), 2.62-2.80 (m, 1H), 2.15 (s, 3H), 1.90-2.02 (m, 5H), 1.50-1.88 (m, 6H).

Workup

  1. customTFA was evaporated
  2. additionEtOAc was added
  3. additionto dilute the mixture
  4. washThe mixture washed with saturated aqueous NaHCO3, brine
  5. dry with materialdry with Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by flash column chromatography (20% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-1fe1dbcd775741a982f357e51a936254
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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