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

HRID 1476621Notes

Reaction equation

HRID 1476621 reaction equation
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[CH:36]=[CH:37][C:38]([O:44][CH3:45])=[C:39](B(O)O)[CH:40]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.Cl[Pd]Cl>[CH2:32]([N:30]1[N:29]=[N:28][C:27]([CH2:26][N:5]2[C:4]3[CH:3]=[C:2]([C:37]4[CH:36]=[C:35]([F:34])[CH:40]=[CH:39][C:38]=4[O:44][CH3:45])[S:10][C:9]=3[C:8](=[O:11])[N:7]([CH:12]3[CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:22])[CH3:23])=[O:19])[CH2:16][CH2:17]3)[C:6]2=[O:25])=[N:31]1)[CH3:33]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27826735-Fluoro-2-methoxyphenylboronic 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

Product 1

HCID 67257950tert-butyl 4-{1-[(2-ethyl-2H-tetrazol-5-yl)methyl]-6-(5-fluoro-2-methoxyphenyl)-2,4-dioxo-1,4-dihydrothieno[3,2-d]pyrimidin-3(2H)-yl}piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 11050900Dichlorobis(tricyclohexylphosphine)pallium (II)CatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

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 (811 mg, compound B101), (5-fluoro-2-methoxyphenyl)boronic acid (280 mg), dichlorobis(tricyclohexylphosphine)palladium (110 mg) and aqueous cesium carbonate solution (1.125 ml, 2.0 M) in DME (10 ml) are reacted according to the procedure described in example B55 to afford the title compound after purification by flash column chromatography [silica gel, elution gradient: cyclohexane/EtOAc, 100/0 to 50/50 to 30/70 (v/v)] as a solid.

Sources & evidence

ORD record
ord-fccbe467666e417b9fdf9e098e37466e
Source dataset
uspto-grants-2015_04
Patent number
US09018175B2

Reaction notes

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