1-methyl-2,4-dioxo-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-(3-(trifluoro methoxy)phenoxy)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carbaldehyde → 5-((4-chlorophenyl)(hydroxy)methyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-(3-(trifluoromethoxy)phenoxy)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 63901Notes

Reaction equation

HRID 63901 reaction equation
[CH3:1][N:2]1[C:7]2[S:8][C:9]([O:13][C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]([F:24])([F:23])[F:22])[CH:15]=3)=[C:10]([CH:11]=[O:12])[C:6]=2[C:5](=[O:25])[N:4]([CH2:26][CH2:27][CH2:28][O:29][CH:30]2[CH2:35][CH2:34][CH2:33][CH2:32][O:31]2)[C:3]1=[O:36].[Cl:37][C:38]1[CH:43]=[CH:42][C:41]([Mg]Br)=[CH:40][CH:39]=1>C1COCC1.C(Cl)Cl.O>[Cl:37][C:38]1[CH:43]=[CH:42][C:41]([CH:11]([OH:12])[C:10]2[C:6]3[C:5](=[O:25])[N:4]([CH2:26][CH2:27][CH2:28][O:29][CH:30]4[CH2:35][CH2:34][CH2:33][CH2:32][O:31]4)[C:3](=[O:36])[N:2]([CH3:1])[C:7]=3[S:8][C:9]=2[O:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]([F:22])([F:23])[F:24])[CH:15]=2)=[CH:40][CH:39]=1

Participants

6

Reactant 2

HCID 1188631081-methyl-2,4-dioxo-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-(3-(trifluoro methoxy)phenoxy)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carbaldehydeHCID 178478191HCID 178478191, compound

Product 1

HCID 1188631245-((4-chlorophenyl)(hydroxy)methyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-(3-(trifluoromethoxy)phenoxy)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 49.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-methyl-2,4-dioxo-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-(3-(trifluoro methoxy)phenoxy)-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidine-5-carbaldehyde (50 mg, 0.095 mmol) in THF (2 mL) was added (4-chlorophenyl)magnesium bromide (0.19 mL, 0.190 mmol). The reaction was stirred for 2 min then diluted with DCM (5 mL) and water (5 mL). The organic layer was dried over Na2SO4 and concentrated to a residue which was purified by chromatography PE/EA (5:1 to 3:1) to give 5-((4-chlorophenyl)(hydroxy)methyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-(3-(trifluoromethoxy)phenoxy)thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (30 mg, 49.5% yield) as a solid. LCMS: [M+-THP-OH] 539 and TR=2.159 min.

Workup

  1. dry with materialThe organic layer was dried over Na2SO4
  2. concentrationconcentrated to a residue which
  3. customwas purified by chromatography PE/EA (5:1 to 3:1)

Sources & evidence

ORD record
ord-19d394a1e9ff41d884bec2899077237d
Source dataset
uspto-grants-2016_09
Patent number
US09447114B2

Reaction notes

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