Ethyl Bromide → tert-butyl 4-{1-[(1-ethyl-1H-tetrazol-5-yl)methyl]-2,4-dioxo-6-phenyl-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl}piperidine-1-carboxylate

HRID 1476582Notes

Reaction equation

[O:1]=[C:2]1[N:7]([CH2:8][C:9]2[N:10]=[N:11][NH:12][N:13]=2)[C:6]2[CH:14]=[C:15]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[S:16][C:5]=2[C:4](=[O:23])[N:3]1[CH:24]1[CH2:29][CH2:28][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]1.[H-].[Li+].Br[CH2:40][CH3:41]>CN(C=O)C>[CH2:40]([N:13]1[C:9]([CH2:8][N:7]2[C:6]3[CH:14]=[C:15]([C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=4)[S:16][C:5]=3[C:4](=[O:23])[N:3]([CH:24]3[CH2:25][CH2:26][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:28][CH2:29]3)[C:2]2=[O:1])=[N:10][N:11]=[N:12]1)[CH3:41].[CH2:40]([N:11]1[N:12]=[N:13][C:9]([CH2:8][N:7]2[C:6]3[CH:14]=[C:15]([C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=4)[S:16][C:5]=3[C:4](=[O:23])[N:3]([CH:24]3[CH2:25][CH2:26][N:27]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:28][CH2:29]3)[C:2]2=[O:1])=[N:10]1)[CH3:41]

Participants

Conditions

Temperature: 40 °C

Procedure

To a solution of the tautomeric mixture of tert-butyl 4-[2,4-dioxo-6-phenyl-1-(2H-tetrazol-5-ylmethyl)-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl]piperidine-1-carboxylate and tert-butyl 4-[2,4-dioxo-6-phenyl-1-(1H-tetrazol-5-ylmethyl)-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl]piperidine-1-carboxylate (255 mg; compound B14b) in DMF (5 ml) under nitrogen atmosphere is added lithium hydride (5.0 mg). After 10 min at RT bromoethane (163 mg) is added. The mixture is stirred for 1.5 h at 40° C. then all volatile materials are removed in vacuo. The residue is purified by flash column chromatography [silica gel, eluation gradient: hexanes/EtOAc/triethylamine, 16/3/1 to 5/4/1 (v/v/v)] to give the two separated isomers tert-butyl 4-{1-[(1-ethyl-1H-tetrazol-5-yl)methyl]-2,4-dioxo-6-phenyl-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl}piperidine-1-carboxylate (compound B15) and tert-butyl 4-{1-[(2-ethyl-2H-tetrazol-5-yl)methyl]-2,4-dioxo-6-phenyl-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl}piperidine-1-carboxylate (compound B14) as solids.

Workup

customall volatile materials are removed in vacuo
customThe residue is purified by flash column chromatography [silica gel, eluation gradient: hexanes/EtOAc/triethylamine, 16/3/1 to 5/4/1 (v/v/v)]

Sources & evidence

ORD record: ord-4a33b3029ef242fe8633239c47786016
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09018175B2

Reaction notes

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