tert-butyl N-(prop-2-yn-1-yl)carbamate → HCID 86670382, compound
Reaction equation
Br[C:2]1[CH:3]=[C:4]([C:22]([OH:31])([C:27]([F:30])([F:29])[F:28])[C:23]([F:26])([F:25])[F:24])[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][N:11]([S:14]([C:17]2[S:18][CH:19]=[CH:20][CH:21]=2)(=[O:16])=[O:15])[CH2:10][CH2:9]1.[C:32]([O:36][C:37]([NH:39][CH2:40][C:41]#[CH:42])=[O:38])([CH3:35])([CH3:34])[CH3:33]>>[S:18]1[CH:19]=[CH:20][CH:21]=[C:17]1[S:14]([N:11]1[CH2:12][CH2:13][N:8]([C:7]2[CH:6]=[CH:5][C:4]([C:22]([OH:31])([C:27]([F:30])([F:29])[F:28])[C:23]([F:26])([F:25])[F:24])=[CH:3][C:2]=2[C:42]#[C:41][CH2:40][NH:39][C:37](=[O:38])[O:36][C:32]([CH3:34])([CH3:33])[CH3:35])[CH2:9][CH2:10]1)(=[O:16])=[O:15]Participants
Procedure
Following the procedure outlined for Example 152, 2-(3-Bromo-4-(4-(thiophen-2-ylsulfonyl)piperazin-1-yl)phenyl)-1,1,1,3,3,3-hexafluoro-2-propanol (Example 69) was coupled to N-(tert-butoxycarbonyl)propargylamine (Aldrich, St. Louis, Mo.) to afford tert-butyl (3-(2-(4-(2-thiophenylsulfonyl)-1-piperazinyl)-5-(2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl)phenyl)-2-propyn-1-yl)carbamate after purification via column chromatography on silica gel (10 to 40% EtOAc in hexanes). 1H NMR (400 MHz, DMSO-d6) δ 8.68 (s, 1H), 8.08 (dd, J=1.00, 5.09 Hz, 1H), 7.69 (dd, J=0.98, 3.72 Hz, 1H), 7.51-7.56 (m, 2H), 7.32 (dd, J=3.91, 4.89 Hz, 2H), 7.07 (d, J=9.39 Hz, 1H), 3.94 (d, J=5.48 Hz, 2H), 3.26-3.29 (m, 4H), 3.12-3.18 (m, 4H), 1.40 (s, 9H); m/z (ESI, +ve ion) 628.1 (M+H)+. GK-GKRP IC50 (Binding)=0.695 μM.
Sources & evidence
- ORD record
- ord-06dc4f7068484b908579b31371ef4327
- Source dataset
- uspto-grants-2013_04
- Patent number
- US08431563B2
Reaction notes
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