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 1476582ノート

反応式

HRID 1476582 の反応式
[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]

参加物

7

反応物 4

HCID 6332Ethyl BromideHCID 62714Lithium hydrideHCID 67258221tert-butyl 4-[2,4-dioxo-6-phenyl-1-(1H-tetrazol-5-ylmethyl)-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl]piperidine-1-carboxylateHCID 178452064HCID 178452064、化合物

生成物 2

HCID 67258320tert-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-carboxylateHCID 67258558tert-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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
40 °C

実験手順

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.

後処理

  1. customall volatile materials are removed in vacuo
  2. 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)]

出典と根拠

ORDレコード
ord-4a33b3029ef242fe8633239c47786016
出典データセット
uspto-grants-2015_04
特許番号
US09018175B2

反応ノート

読み込み中…