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

HRID 1676365Notes

Reaction equation

HRID 1676365 reaction equation
[F:1][C:2]1[CH:30]=[C:29]([NH:31][C:32]([C:34]2[C:39](=[O:40])[N:38]([C:41]3[CH:46]=[CH:45][C:44]([F:47])=[CH:43][CH:42]=3)[N:37]=[CH:36][CH:35]=2)=[O:33])[CH:28]=[CH:27][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12]([CH:14]3[CH2:19][CH2:18][N:17](C(OC(C)(C)C)=O)[CH2:16][CH2:15]3)[S:13][C:6]=12.C(O)(C(F)(F)F)=O>>[F:1][C:2]1[CH:30]=[C:29]([NH:31][C:32]([C:34]2[C:39](=[O:40])[N:38]([C:41]3[CH:42]=[CH:43][C:44]([F:47])=[CH:45][CH:46]=3)[N:37]=[CH:36][CH:35]=2)=[O:33])[CH:28]=[CH:27][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[CH:11]=[C:12]([CH:14]3[CH2:15][CH2:16][NH:17][CH2:18][CH2:19]3)[S:13][C:6]=12

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67347399Tert-butyl 4-(7-(2-fluoro-4-(1-(4-fluorophenyl)-6-oxo-1,6-dihydropyridazine-5-carboxamido)phenoxy)thieno[3,2-b]pyridin-2-yl)piperidine-1-carboxylate

Product 1

HCID 58949489N-(3-fluoro-4-(2-(piperidin-4-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxamideYield 52.1%

Procedure

A round-bottomed flask was charged with tert-butyl 4-(7-(2-fluoro-4-(1-(4-fluorophenyl)-6-oxo-1,6-dihydropyridazine-5-carboxamido)phenoxy)thieno[3,2-b]pyridin-2-yl)piperidine-1-carboxylate (87.3 mg, 0.132 mmol) and CF3COOH (5 mL). The reaction mixture was stirred at room temperature until the starting material had been consumed (one hour). Then the solvent was removed and the residue was purified by silica gel chromatography (dichloromethane/7 M NH3 in MeOH from 50/1 to 10/1, v/v) to afford product (38.5 mg, 52%). LRMS (APCI pos): >99% purity, 254 nm, m/e 560 (M+1). 1H NMR (400 MHz, CDCl3) δ 11.83 (s, 1H), 8.44 (d, 1H), 8.41 (d, 1H), 8.24 (d, 1H), 7.95 (dd, 1H), 7.61 (m, 2H), 7.38 (m, 1H), 7.21-7.28 (m, 4H), 6.46 (d, 1H), 3.23 (m, 2H), 3.06 (m, 1H), 2.79 (m, 2H), 2.11 (m, 2H), 1.77 (m, 2H),

Workup

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

Sources & evidence

ORD record
ord-9d5e6707b1824f56b00b0c4f0091015b
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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