Phenylacetyl isothiocyanate → 2-(7-(2-Fluoro-4-(3-(2-phenylacetyl)thioureido)phenoxy)thieno[3,2-b]pyridin-2-yl)pyridine 1-oxide
Reaction equation
C(OC([NH:8][C:9]1[CH:31]=[CH:30][C:12]([O:13][C:14]2[CH:19]=[CH:18][N:17]=[C:16]3[CH:20]=[C:21]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][N+:24]=4[O-:29])[S:22][C:15]=23)=[C:11]([F:32])[CH:10]=1)=O)(C)(C)C.C(Cl)Cl.C(O)(C(F)(F)F)=O.[C:43]1([CH2:49][C:50]([N:52]=[C:53]=[S:54])=[O:51])[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1>>[F:32][C:11]1[CH:10]=[C:9]([NH:8][C:53]([NH:52][C:50](=[O:51])[CH2:49][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)=[S:54])[CH:31]=[CH:30][C:12]=1[O:13][C:14]1[CH:19]=[CH:18][N:17]=[C:16]2[CH:20]=[C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][N+:24]=3[O-:29])[S:22][C:15]=12Participants
4
Reactant 3
Product 1
Procedure
A mixture of 432 (243 mg, 0.53 mmol) in 3:1 mixture of DCM/TFA (8 mL) was stirred at room temperature for 1 hour and concentrated under reduced pressure. The resultant solid was dissolved in 1:1 mixture of EtOH/toluene (10 mL) and treated with 2-phenylacetyl isothiocyanate (140 mg, 0.8 mmol). The reaction mixture was stirred for 1 hour at room temperature and concentrated. The residue was purified by flash chromatography using the gradient 0-20% MeOH in EtOAc as an eluent yielding 430 (101 mg, 36% yield). MeOH-d4/CDCl3 (1:1) 8.5 (d, 1H, J=5.4 Hz), 8.38 (m, 3H), 8.0 (d, 1H, 11.9 Hz), 7.62 (t, 1H, J=7.7 Hz), 7.45 (m, 2H), 7.2-7.4 (m, 6H), 6.64 (5.1 Hz), 3.75 (s, 2H). LCMS: (M+H) 531.2.
Workup
- concentrationconcentrated under reduced pressure
- dissolutionThe resultant solid was dissolved in 1:1 mixture of EtOH/toluene (10 mL)
- stirringThe reaction mixture was stirred for 1 hour at room temperature
- concentrationconcentrated
- customThe residue was purified by flash chromatography
Sources & evidence
- ORD record
- ord-6d5e3a0fdaef4db1ad03b2cdfa1fd770
- Source dataset
- uspto-grants-2010_09
- Patent number
- US07790729B2
Reaction notes
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