Trifluoroacetic acid → N-methyl-1-(5-(thiophen-2-yl)tetrazolo[1,5-a]pyrazin-8-yl)azetidin-3-amine
Reaction equation
[CH3:1][N:2]([CH:10]1[CH2:13][N:12]([C:14]2[C:15]3[N:16]([N:25]=[N:26][N:27]=3)[C:17]([C:20]3[S:21][CH:22]=[CH:23][CH:24]=3)=[CH:18][N:19]=2)[CH2:11]1)C(=O)OC(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[CH3:1][NH:2][CH:10]1[CH2:11][N:12]([C:14]2[C:15]3[N:16]([N:25]=[N:26][N:27]=3)[C:17]([C:20]3[S:21][CH:22]=[CH:23][CH:24]=3)=[CH:18][N:19]=2)[CH2:13]1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
A 2 L round bottom flask was charged with tert-butyl methyl(1-(5-(thiophen-2-yl)tetrazolo[1,5-a]pyrazin-8-yl)azetidin-3-yl)carbamate (50 g, 0.13 mol) and dichloromethane (500 mL). To the solution was added trifluoroacetic acid (100 mL). The resulting slurry was stirred at room temperature for 2.5 h. Work-up: the reaction mixture was concentrated in vacuo. The residue was suspended in water (500 L) and treated with solid Na2CO3 (pH 10-11, there was un-dissolved Na2CO3 remaining). The solid was collected by filtration, re-suspended in water (500 mL×2) with stirring to remove Na2CO3. It was further washed with EtOH (500 mL), and dried to afford 27 g (73%) of the product as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ: 8.19 (s, 1H), 7.96 (dd, J=4.0, 0.8 Hz, 1H), 7.76 (dd, J=4.8, 0.8 Hz, 1H), 7.27 (dd, J=4.8, 4.0 Hz, 1H), 4.60 (br, 2H), 4.18 (br, 2H), 3.73 (m, 1H), 2.43 (br, 1H), 2.29 (s, 3H). MS m/z: 288 (M+H+).
Workup
- concentrationthe reaction mixture was concentrated in vacuo
- additiontreated with solid Na2CO3 (pH 10-11, there was un-dissolved Na2CO3 remaining)
- filtrationThe solid was collected by filtration
- stirringwith stirring
- customto remove Na2CO3
- washIt was further washed with EtOH (500 mL)
- customdried
Sources & evidence
- ORD record
- ord-6fc36dc68d424e87a52278a8a4304a0e
- Source dataset
- uspto-grants-2013_10
- Patent number
- US08569300B2
Reaction notes
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