3-Methylbutanal → 5-(1-hydroxy-3-methylbutyl)-1-methyl-6-(5-methylpyridin-3-yloxy)-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione
Reaction equation
[CH3:1][N:2]1[C:7]2[N:8]=[CH:9][C:10]([O:12][C:13]3[CH:14]=[N:15][CH:16]=[C:17]([CH3:19])[CH:18]=3)=[CH:11][C:6]=2[C:5](=[O:20])[N:4]([CH2:21][CH2:22][CH2:23][O:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][O:26]2)[C:3]1=[O:31].[Li+].CC([N-]C(C)C)C.[CH3:40][CH:41]([CH3:45])[CH2:42][CH:43]=[O:44]>C1COCC1.C(Cl)Cl.O>[OH:44][CH:43]([C:11]1[C:6]2[C:5](=[O:20])[N:4]([CH2:21][CH2:22][CH2:23][O:24][CH:25]3[CH2:30][CH2:29][CH2:28][CH2:27][O:26]3)[C:3](=[O:31])[N:2]([CH3:1])[C:7]=2[N:8]=[CH:9][C:10]=1[O:12][C:13]1[CH:14]=[N:15][CH:16]=[C:17]([CH3:19])[CH:18]=1)[CH2:42][CH:41]([CH3:45])[CH3:40]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- -78 °C
Procedure
To a solution of 1-methyl-6-(5-methylpyridin-3-yloxy)-3-(3-(tetrahydro-2H-pyran-2-yloxy) propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (See Compound 27, step 1, 100 mg, 0.23 mmol) in THF (5 mL) at −78° C. was added LDA (2M in THF, 0.48 mL, 0.940 mmol) dropwise. The reaction was stirred at −78° C. for 1 h then 3-methylbutanal (40 mg, 0.470 mmol) in THF (1 mL) was added. The reaction was stirred at −78° C. for 45 min then diluted with DCM (10 mL) and water (10 mL). The organic layer was dried over Na2SO4 and concentrated to give 5-(1-hydroxy-3-methylbutyl)-1-methyl-6-(5-methylpyridin-3-yloxy)-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (120 mg, 90% yield) as a solid. LCMS: [M+-THP] 429 and TR=1.769 min. Used without further purification.
Workup
- stirringThe reaction was stirred at −78° C. for 45 min
- dry with materialThe organic layer was dried over Na2SO4
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-dd177d36e1614f48a9df7e7462b4edb7
- Source dataset
- uspto-grants-2016_09
- Patent number
- US09440972B2
Reaction notes
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