Tetrahydro-4H-pyran-4-one → 4-(6-((2H-pyran-4(3H,5H,6H)-ylidene)methyl)-2-chloropyrido[3,2-d]pyrimidin-4-yl)morpholine

HRID 1043639Notes

Reaction equation

HRID 1043639 reaction equation
[Cl:1][C:2]1[N:3]=[C:4]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)[C:5]2[N:11]=[C:10]([CH2:12]P(=O)(OC)OC)[CH:9]=[CH:8][C:6]=2[N:7]=1.C([N-]C(C)C)(C)C.[Li+].[O:33]1[CH2:38][CH2:37][C:36](=O)[CH2:35][CH2:34]1>C1COCC1>[O:33]1[CH2:38][CH2:37][C:36](=[CH:12][C:10]2[CH:9]=[CH:8][C:6]3[N:7]=[C:2]([Cl:1])[N:3]=[C:4]([N:19]4[CH2:20][CH2:21][O:22][CH2:23][CH2:24]4)[C:5]=3[N:11]=2)[CH2:35][CH2:34]1

Participants

5

Reactant 3

HCID 121599Tetrahydro-4H-pyran-4-oneHCID 2724682Lithium diisopropylamideHCID 58405032Dimethyl (2-chloro-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methylphosphonate

Product 1

HCID 584050234-(6-((2H-pyran-4(3H,5H,6H)-ylidene)methyl)-2-chloropyrido[3,2-d]pyrimidin-4-yl)morpholine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of dimethyl (2-chloro-4-morpholinopyrido[3,2-d]pyrimidin-6-yl)methylphosphonate from Example 117 (0.45 g) in anhydrous THF (6 mL) at 0° C. was added 2.0 M of lithium diisopropylamide in tetrahydrofuran (1.5 eq). The resulting solution was allowed to warm to RT before adding a solution of dihydro-2H-pyran-4(3H)-one (1.5 eq) in anhydrous THF (3 mL). The reaction mixture was stirred at room temperature for 1 h, then partitioned between brine and Ethyl Acetate. The organic layer was isolated, dried (MgSO4), concentrated and recrystallized from methanol. The light yellow solid was filtered and collected to give 0.36 g of 4-(6-((2H-pyran-4(3H,5H,6H)-ylidene)methyl)-2-chloropyrido[3,2-d]pyrimidin-4-yl)morpholine as a light yellow solid.

Workup

  1. custompartitioned between brine and Ethyl Acetate
  2. customThe organic layer was isolated
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customrecrystallized from methanol
  6. filtrationThe light yellow solid was filtered
  7. customcollected

Sources & evidence

ORD record
ord-7e9050b21835481eaf1804f6363ad662
Source dataset
uspto-grants-2013_10
Patent number
US08563540B2

Reaction notes

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