4-Chlorobenzaldehyde → 5-((4-chlorophenyl)(hydroxy)methyl)-6-isopropoxy-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 60489Notes

Reaction equation

HRID 60489 reaction equation
[CH:1]([O:4][C:5]1[CH:27]=[N:26][C:8]2[N:9]([CH3:25])[C:10](=[O:24])[N:11]([CH2:14][CH2:15][CH2:16][O:17][CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][O:19]3)[C:12](=[O:13])[C:7]=2[CH:6]=1)([CH3:3])[CH3:2].[Li+].CC([N-]C(C)C)C.[Cl:36][C:37]1[CH:44]=[CH:43][C:40]([CH:41]=[O:42])=[CH:39][CH:38]=1>C1COCC1>[Cl:36][C:37]1[CH:44]=[CH:43][C:40]([CH:41]([OH:42])[C:6]2[C:7]3[C:12](=[O:13])[N:11]([CH2:14][CH2:15][CH2:16][O:17][CH:18]4[CH2:23][CH2:22][CH2:21][CH2:20][O:19]4)[C:10](=[O:24])[N:9]([CH3:25])[C:8]=3[N:26]=[CH:27][C:5]=2[O:4][CH:1]([CH3:3])[CH3:2])=[CH:39][CH:38]=1

Participants

5

Reactant 3

HCID 77264-ChlorobenzaldehydeHCID 2724682Lithium diisopropylamideHCID 1188754856-isopropoxy-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

Product 1

HCID 1188755225-((4-chlorophenyl)(hydroxy)methyl)-6-isopropoxy-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 53.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 6-isopropoxy-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (87 mg, 0.23 mmol) in THF (5 mL) cooled to −78° C. was added LDA (2.0 M in THF, 0.6 mL, 1.15 mmol) dropwise. The reaction was stirred at −78° C. for 1 h then a solution of 4-chlorobenzaldehyde (64.8 mg, 0.46 mmol) in THF (1 mL) was added dropwise. The reaction was stirred at −78° C. for 1 h, quenched with aq. NH4Cl (5 mL), diluted with water (25 mL) then extracted with EA (3×25 mL). The combined organic layers were dried over Na2SO4 and concentrated to a residue which was purified by Prep TLC eluted with PE/EA (1:2) to give 5-((4-chlorophenyl)(hydroxy)methyl)-6-isopropoxy-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy) propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (64 mg, 53.6% yield) as a white solid. LCMS: [M+-THP-OH] 416 and TR=3.210 min. Used without further purification.

Workup

  1. stirringThe reaction was stirred at −78° C. for 1 h
  2. customquenched with aq. NH4Cl (5 mL)
  3. additiondiluted with water (25 mL)
  4. extractionthen extracted with EA (3×25 mL)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. concentrationconcentrated to a residue which
  7. customwas purified by Prep TLC
  8. washeluted with PE/EA (1:2)

Sources & evidence

ORD record
ord-37f61555bbc9415e8f604774904e04e5
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Reaction notes

Loading…