Trifluoroacetic acid → HCID 178480246, compound

HRID 2241346Notes

Reaction equation

HRID 2241346 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]5[C:28](=[O:40])[N:29]([C:33]6[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=6)[N:30]=[CH:31][CH:32]=5)=[O:26])=[CH:20][C:19]=4[F:41])=[C:11]3[C:10]([CH:42]3[CH2:47][CH2:46][N:45]([CH3:48])[CH2:44][CH2:43]3)=[N:9]2)=CC=1.C(O)(C(F)(F)F)=O>>[F:41][C:19]1[CH:20]=[C:21]([NH:24][C:25]([C:27]2[C:28](=[O:40])[N:29]([C:33]3[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=3)[N:30]=[CH:31][CH:32]=2)=[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]([CH:42]3[CH2:47][CH2:46][N:45]([CH3:48])[CH2:44][CH2:43]3)[C:11]=12

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68514688HCID 68514688, compound

Product 1

HCID 178480246HCID 178480246, compoundYield 23.8%

Conditions

Temperature
80 °C

Procedure

A 50 mL round-bottomed flask was charged with N-(4-(1-(4-methoxybenzyl)-3-(1-methylpiperidin-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide (16.3 mg, 0.0241 mmol) and CF3COOH (5 mL). The reaction mixture was stirred at 80° C. overnight. The solvent was removed and the residue was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 50/1 to 10/1, v/v) to afford product, which was further purified by preparative HPLC to afford the desired product (3.2 mg, 16.9%). LRMS (APCI pos): >99% purity, 254 nm, m/e 558 (M+1). 1H NMR (400 MHz, CD3OD) δ 11.94 (s, 1H), 8.24-8.36 (m, 3H), 8.03 (dd, 1H), 7.65 (m, 2H), 7.49 (m, 1H), 7.41 (m, 1H), 7.22-7.30 (m, 2H), 6.31 (d, 1H), 3.62 (m, 2H), 3.45 (m, 1H), 3.14-3.26 (m, 2H), 2.87 (s, 3H), 2.39-2.58 (m, 2H), 2.14-2.32 (m, 2H).

Workup

  1. customThe solvent was removed
  2. customthe residue was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 50/1 to 10/1
  3. customv/v) to afford product, which
  4. customwas further purified by preparative HPLC

Sources & evidence

ORD record
ord-2966a1f1738b4255bb1d3a796bd0c202
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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