4-Fluorobenzaldehyde → HCID 118875496, compound

HRID 60473Notes

Reaction equation

HRID 60473 reaction equation
[Cl:1][C:2]1[CH:31]=[CH:30][C:5]([O:6][C:7]2[CH:29]=[N:28][C:10]3[N:11]([CH3:27])[C:12](=[O:26])[N:13]([CH2:16][CH2:17][CH2:18][O:19][CH:20]4[CH2:25][CH2:24][CH2:23][CH2:22][O:21]4)[C:14](=[O:15])[C:9]=3[CH:8]=2)=[CH:4][CH:3]=1.[Li+].CC([N-]C(C)C)C.[F:40][C:41]1[CH:48]=[CH:47][C:44]([CH:45]=[O:46])=[CH:43][CH:42]=1>C1COCC1>[Cl:1][C:2]1[CH:31]=[CH:30][C:5]([O:6][C:7]2[CH:29]=[N:28][C:10]3[N:11]([CH3:27])[C:12](=[O:26])[N:13]([CH2:16][CH2:17][CH2:18][O:19][CH:20]4[CH2:25][CH2:24][CH2:23][CH2:22][O:21]4)[C:14](=[O:15])[C:9]=3[C:8]=2[CH:45]([C:44]2[CH:47]=[CH:48][C:41]([F:40])=[CH:42][CH:43]=2)[OH:46])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 680234-FluorobenzaldehydeHCID 2724682Lithium diisopropylamideHCID 118875532HCID 118875532, compound

Product 1

HCID 118875496HCID 118875496, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a solution of 6-(4-chlorophenoxy)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (110 mg, 0.25 mmol) in THF (5 mL) at −78° C. was added LDA (2.0 M in THF, 0.63 mL, 1.25 mmol) dropwise. The reaction was stirred at −78° C. for 1 h then a solution of 4-fluorobenzaldehyde (62 mg, 0.50 mmol) in THF (1 mL) was added dropwise. The reaction was stirred at −78° C. for 1 h, quenched with sat. aq. NH4Cl (5 mL) then diluted with EA (30 mL) and water (30 mL). The organic layer was dried over Na2SO4 and concentrated to give a residue which was purified by chromatography eluted with PE/EA (7:1) to give 6-(4-chlorophenoxy)-5-((4-fluorophenyl)(hydroxy)methyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (55 mg, 40% yield) as a solid. LCMS: [M++Na] 592 and TR=3.372 min.

Workup

  1. stirringThe reaction was stirred at −78° C. for 1 h
  2. customquenched with sat. aq. NH4Cl (5 mL)
  3. additionthen diluted with EA (30 mL) and water (30 mL)
  4. dry with materialThe organic layer was dried over Na2SO4
  5. concentrationconcentrated
  6. customto give a residue which
  7. customwas purified by chromatography
  8. washeluted with PE/EA (7:1)

Sources & evidence

ORD record
ord-caf28c57209a43b9833874a8dc811b7b
Source dataset
uspto-grants-2016_09
Patent number
US09440972B2

Reaction notes

Loading…