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

HRID 2387817Notes

Reaction equation

HRID 2387817 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[F:20])=[C:4]([NH:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[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[F:20])=[C:4]([NH:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[N:3]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 66819400Methyl 4-((2-amino-4-methyl-6-(pentylamino)pyrimidin-5-yl)methyl)-3-fluorobenzoate

Product 1

HCID 66819207(4-((2-Amino-4-methyl-6-(pentylamino)pyrimidin-5-yl)methyl)-3-fluorophenyl)methanolYield 60.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of the product from step (iv) (1.52 g) in THF (30 mL) was added portionwise to a stirred solution of lithium aluminium hydride (1M in THF; 8.43 mL) in THF (30 mL) at 0° C. under nitrogen. The resulting mixture was stirred at rt for 2 h. EtOAc (10 mL) was added cautiously to the reaction mixture and the mixture added portionwise to 2M NaOH (100 mL). The mixture was stirred for 30 min and the aqueous solution was extracted with EtOAc. The combined organic phase was dried, filtered and evaporated. The crude product was purified by chromatography eluting with 2 to 5% MeOH in acetonitrile to give the subtitle compound as a yellow oil 0.85 g.

Workup

  1. stirringThe mixture was stirred for 30 min
  2. extractionthe aqueous solution was extracted with EtOAc
  3. customThe combined organic phase was dried
  4. filtrationfiltered
  5. customevaporated
  6. customThe crude product was purified by chromatography
  7. washeluting with 2 to 5% MeOH in acetonitrile

Sources & evidence

ORD record
ord-c83d3dcc2f7149f3aad628644dd895a4
Source dataset
uspto-grants-2012_09
Patent number
US08268990B2

Reaction notes

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