Trifluoroacetic acid → N-(3-Fluoro-4-(2-(4-oxocyclohexyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide

HRID 1676376Notes

Reaction equation

HRID 1676376 reaction equation
O1[C:5]2([CH2:10][CH2:9][CH:8]([C:11]3[S:19][C:18]4[C:13](=[N:14][CH:15]=[CH:16][C:17]=4[O:20][C:21]4[CH:26]=[CH:25][C:24]([NH:27][C:28]([C:30]5[C:31](=[O:43])[N:32]([C:36]6[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=6)[N:33]=[CH:34][CH:35]=5)=[O:29])=[CH:23][C:22]=4[F:44])[CH:12]=3)[CH2:7][CH2:6]2)[O:4]CC1.C(O)(C(F)(F)F)=O>>[F:44][C:22]1[CH:23]=[C:24]([NH:27][C:28]([C:30]2[C:31](=[O:43])[N:32]([C:36]3[CH:37]=[CH:38][C:39]([F:42])=[CH:40][CH:41]=3)[N:33]=[CH:34][CH:35]=2)=[O:29])[CH:25]=[CH:26][C:21]=1[O:20][C:17]1[CH:16]=[CH:15][N:14]=[C:13]2[CH:12]=[C:11]([CH:8]3[CH2:7][CH2:6][C:5](=[O:4])[CH2:10][CH2:9]3)[S:19][C:18]=12

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67347914N-(4-(2-(1,4-dioxaspiro[4.5]decan-8-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide

Product 1

HCID 58949495N-(3-Fluoro-4-(2-(4-oxocyclohexyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamideYield 42.9%

Procedure

A round-bottomed flask was charged with N-(4-(2-(1,4-dioxaspiro[4.5]decan-8-yl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide (13.3 mg, 0.0216 mmol) and CF3COOH (5 mL). The reaction mixture was stirred at room temperature the starting material had been consumed (1 hour). Then 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 product (5.3 mg, 42.9%). LRMS (APCI pos): >99% purity, 254 nm, m/e 573 (M+1). 1H NMR (400 MHz, CD3OD) δ 11.84 (s, 1H), 8.46 (d, 1H), 8.41 (d, 1H), 8.24 (d, 1H), 7.95 (dd, 1H), 7.57-7.65 (m, 2H), 7.39 (m, 1H), 7.34 (s, 1H), 7.21-7.30 (m, 3H), 6.49 (d, 1H), 3.45 (m, 1H), 2.34-2.61 (m, 6H), 2.09 (m, 2H).

Workup

  1. customhad been consumed (1 hour)
  2. customThen the solvent was removed
  3. customthe residue was purified by silica gel chromatography (DCM/7 M NH3 in MeOH from 50/1 to 10/1

Sources & evidence

ORD record
ord-6bddb25c74f748829fc947ed7056efaa
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

Loading…