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 1476582노트

반응식

HRID 1476582 반응식
[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]

참가 물질

7

반응물 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, 화합물

생성물 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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
40 °C

실험 절차

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.

후처리

  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)]

출처 및 근거

ORD 기록
ord-4a33b3029ef242fe8633239c47786016
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09018175B2

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