Ethyl Acetate → (4-((2-Amino-4-methyl-6-(pentylamino)pyrimidin-5-yl)methyl)-3-methoxyphenyl)methanol

HRID 1617155Notes

Reaction equation

HRID 1617155 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([CH3:8])[C:5]([CH2:9][C:10]2[CH:19]=[CH:18][C:13]([C:14](OC)=[O:15])=[CH:12][C:11]=2[O:20][CH3:21])=[C:4]([NH:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[N:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].CCOC(C)=O.[OH-].[Na+]>C1COCC1>[NH2:1][C:2]1[N:7]=[C:6]([CH3:8])[C:5]([CH2:9][C:10]2[CH:19]=[CH:18][C:13]([CH2:14][OH:15])=[CH:12][C:11]=2[O:20][CH3:21])=[C:4]([NH:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[N:3]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 49806175Methyl 4-((2-amino-4-methyl-6-(pentylamino)pyrimidin-5-yl)methyl)-3-methoxybenzoate

Product 1

HCID 66819929(4-((2-Amino-4-methyl-6-(pentylamino)pyrimidin-5-yl)methyl)-3-methoxyphenyl)methanolYield 42.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of the product from step (iv) (2.4 g) in THF (50 mL) was added portionwise over 10 min to a stirred solution of lithium aluminum hydride (1M in THF; 12.89 mL) in THF (50 mL) at 0° C. under nitrogen. The resulting mixture was stirred at 0° C. for 10 min and then at rt for 1 h. EtOAc (20 mL) was added portionwise over 10 min and the resulting mixture stirred for a further 20 min. The mixture was added portionwise to 2M NaOH (300 mL) and stirred for 30 min. The resulting suspension was filtered through a pad of celite and the resulting biphasic filtrate separated. The aqueous phase was extracted with EtOAc (200 mL) and the combined organic phase was dried, filtered and evaporated. The crude product was purified by chromatography, eluting with 5 to 10% MeOH in DCM. to afford the subtitle compound as a colorless gum 0.94 g.

Workup

  1. waitat rt for 1 h
  2. stirringthe resulting mixture stirred for a further 20 min
  3. stirringstirred for 30 min
  4. filtrationThe resulting suspension was filtered through a pad of celite
  5. customthe resulting biphasic filtrate separated
  6. extractionThe aqueous phase was extracted with EtOAc (200 mL)
  7. customthe combined organic phase was dried
  8. filtrationfiltered
  9. customevaporated
  10. customThe crude product was purified by chromatography
  11. washeluting with 5 to 10% MeOH in DCM

Sources & evidence

ORD record
ord-d54ebabc81304d9ead6a49f2eb4eca0f
Source dataset
uspto-grants-2014_07
Patent number
US08765939B2

Reaction notes

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