Cesium carbonate → tert-butyl 4-[6-(2,3-difluorophenyl)-1-[(2-ethyl-2H-tetrazol-5-yl)methyl]-2,4-dioxo-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl]piperidine-1-carboxylate

HRID 1476625노트

반응식

HRID 1476625 반응식
Br[C:2]1[S:10][C:9]2[C:8](=[O:11])[N:7]([CH:12]3[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]3)[C:6](=[O:25])[N:5]([CH2:26][C:27]3[N:28]=[N:29][N:30]([CH2:32][CH3:33])[N:31]=3)[C:4]=2[CH:3]=1.[F:34][C:35]1[C:40]([F:41])=[CH:39][CH:38]=[CH:37][C:36]=1B(O)O.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.Cl[Pd]Cl>[F:34][C:35]1[C:40]([F:41])=[CH:39][CH:38]=[CH:37][C:36]=1[C:2]1[S:10][C:9]2[C:8](=[O:11])[N:7]([CH:12]3[CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[O:19])[CH2:16][CH2:17]3)[C:6](=[O:25])[N:5]([CH2:26][C:27]3[N:28]=[N:29][N:30]([CH2:32][CH3:33])[N:31]=3)[C:4]=2[CH:3]=1

참가 물질

6

반응물 3

HCID 10796Cesium carbonateHCID 2734333(2,3-Difluorophenyl)boronic acidHCID 67258602Tert-butyl 4-[6-bromo-1-[(2-ethyl-2H-tetrazol-5-yl)methyl]-2,4-dioxo-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl]piperidine-1-carboxylate

생성물 1

HCID 67257703tert-butyl 4-[6-(2,3-difluorophenyl)-1-[(2-ethyl-2H-tetrazol-5-yl)methyl]-2,4-dioxo-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl]piperidine-1-carboxylate

시약·촉매·용매 2

HCID 11050900Dichlorobis(tricyclohexylphosphine)pallium (II)촉매HCID 80711,2-Dimethoxyethane용매

실험 절차

Tert-butyl 4-{6-bromo-1-[(2-ethyl-2H-tetrazol-5-yl)methyl]-2,4-dioxo-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl}piperidine-1-carboxylate (405 mg, compound B101), (2,3-difluorophenyl)boronic acid (118 mg), dichlorobis(tricyclohexylphosphine)palladium (28 mg) and aqueous cesium carbonate solution (0.563 ml, 2.0 M) in DME (10 ml) are reacted according to the procedure described in example B55 to afford the title compound after two times purification by flash column chromatography [silica gel, elution gradient: cyclohexane/EtOAc, 100/0 to 50/50 to 30/70 (v/v) and amino phase silica gel elution gradient: cyclohexane/EtOAc, 100/0 to 50/50 to 30/70 (v/v)] as a solid.

출처 및 근거

ORD 기록
ord-6abc6d5dc34448a08afb2df6bd73d6e4
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09018175B2

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