Trifluoroacetic acid → HCID 59304262, compound

HRID 2241364Notes

Reaction equation

HRID 2241364 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:32](=[O:33])[N:31]([C:34]6[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=6)[N:30]=[CH:29][CH:28]=5)=[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](C)[C:49](=O)OC(C)(C)C)[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:32](=[O:33])[N:31]([C:34]3[CH:35]=[CH:36][C:37]([F:40])=[CH:38][CH:39]=3)[N:30]=[CH:29][CH:28]=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]([N:42]3[CH2:47][CH2:46][CH:45]([NH:48][CH3:49])[CH2:44][CH2:43]3)[C:11]=12

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68514091HCID 68514091, compound

Product 1

HCID 59304262HCID 59304262, compoundYield 24.4%

Conditions

Temperature
80 °C

Procedure

A round-bottomed flask was charged with tert-butyl 1-(1-(4-methoxybenzyl)-4-(2-fluoro-4-(1-(4-fluorophenyl)-6-oxo-1,6-dihydropyridazine-5-carboxamido)phenoxy)-1H-pyrazolo[3,4-b]pyridin-3-yl)piperidin-4-yl(methyl)carbamate (98.5 mg, 0.124 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 give the product, which was not pure enough. The impure product was further purified by preparative HPLC to afford product (17.3 mg, 24.3%). LRMS (APCI pos) m/e 573 (M+1). 1H NMR (400 MHz, CD3OD δ 11.97 (s, 1H), 8.38 (d, 1H), 8.33 (d, 1H), 8.25 (d, 1H), 8.08 (m, 1H), 7.65 (m, 2H), 7.48 (d, 1H), 7.40 (m, 1H), 7.28 (m, 2H), 6.28 (d, 1H), 4.10 (m, 2H), 3.32 (m, 1H), 3.01 (m, 2H), 2.72 (s, 3H), 2.18 (m, 2H), 2.81 (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 give the product, which
  4. customThe impure product was further purified by preparative HPLC

Sources & evidence

ORD record
ord-d609499a31054a1184bf007a78ff7e0c
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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