3-Chlorophenol → 6-(3-chlorophenoxy)-1-methyl-2,4-dioxo-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carbaldehyde

HRID 63886Notes

Reaction equation

Br[C:2]1[S:23][C:5]2[N:6]([CH3:22])[C:7](=[O:21])[N:8]([CH2:11][CH2:12][CH2:13][O:14][CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][O:16]3)[C:9](=[O:10])[C:4]=2[C:3]=1[CH:24]=[O:25].C([O-])([O-])=O.[K+].[K+].[Cl:32][C:33]1[CH:34]=[C:35]([OH:39])[CH:36]=[CH:37][CH:38]=1>CN(C=O)C.CC(=O)OCC.O>[Cl:32][C:33]1[CH:34]=[C:35]([CH:36]=[CH:37][CH:38]=1)[O:39][C:2]1[S:23][C:5]2[N:6]([CH3:22])[C:7](=[O:21])[N:8]([CH2:11][CH2:12][CH2:13][O:14][CH:15]3[CH2:20][CH2:19][CH2:18][CH2:17][O:16]3)[C:9](=[O:10])[C:4]=2[C:3]=1[CH:24]=[O:25]

Participants

Conditions

Temperature: 65 °C

Procedure

To a mixture of 6-bromo-1-methyl-2,4-dioxo-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carbaldehyde (100 mg, 0.23 mmol), K2CO3 (159 mg, 1.15 mmol) in DMF (3 mL) was added 3-chlorophenol (90 mg, 0.70 mmol). The reaction was heated at 65° C. for 1 h, cooled to RT then diluted with EA (30 mL) and water (30 mL). The organic layer was dried over Na2SO4 and concentrated to a residue which was purified by chromatography and eluted with PE/EA (5:1) to give 6-(3-chlorophenoxy)-1-methyl-2,4-dioxo-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carbaldehyde (65 mg, 58.6% yield) as a yellow oil. LCMS: MH+ 479 and TR=1.836 min.

Workup

temperaturecooled to RT
dry with materialThe organic layer was dried over Na2SO4
concentrationconcentrated to a residue which
customwas purified by chromatography
washeluted with PE/EA (5:1)

Sources & evidence

ORD record: ord-3f9c4adfa7ee432cb258177f1e5d2823
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09447114B2

Reaction notes

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