Trifluoroacetic acid → 5-[4,5-Dimethoxy-2-(1-methyl-2-phenyl-ethyl)-benzyl]-pyrimidine-2,4-diamine

HRID 1677240Notes

Reaction equation

HRID 1677240 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([C:9]([C:11]2[CH:16]=[C:15]([O:17][CH3:18])[C:14]([O:19][CH3:20])=[CH:13][C:12]=2[CH:21]([CH3:29])[CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=O)=[CH:4][N:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3].FC(F)(F)C(O)=O.C([SiH](CC)CC)C.C([O-])([O-])=O.[K+].[K+]>C1COCC1.C(Cl)Cl>[CH3:20][O:19][C:14]1[C:15]([O:17][CH3:18])=[CH:16][C:11]([CH2:9][C:5]2[C:6]([NH2:8])=[N:7][C:2]([NH2:1])=[N:3][CH:4]=2)=[C:12]([CH:21]([CH3:29])[CH2:22][C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:13]=1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 12052TriethylsilaneHCID 21226445Aluminium lithium hydrideHCID 59598674(2,4-Diamino-pyrimidin-5-yl)-[4,5-dimethoxy-2-(1-methyl-2-phenyl-ethyl)-phenyl]-methanone

Product 1

HCID 161191675-[4,5-Dimethoxy-2-(1-methyl-2-phenyl-ethyl)-benzyl]-pyrimidine-2,4-diamineYield 58%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (2,4-diamino-pyrimidin-5-yl)-[4,5-dimethoxy-2-(1-methyl-2-phenyl-ethyl)-phenyl]-methanone (0.413 g, 0.4 mmol) in 10 mL THF was added LiAlH4 (0.73 mL, 1.0 M in THF) over 5 min. After gas evolution ceased the mixture was warmed to reflux. After 3 h the mixture was cooled to 0° C. and quenched by the Fieser method. After 30 min the mixture was filtered through a pad of celite and concentrated in vacuo to give a crude white solid. To a solution of this solid in 5 mL CH2Cl2 was added trifluoroacetic acid (1.1 mL, 14.0 mmol) followed by triethylsilane (0.4 mL, 2.8 mmol). After 30 min 50 mL 10% K2CO3 was as added and the mixture was extracted with ethyl acetate and washed with brine. The combined organics were dried over Na2SO4, filtered and concentrated in vacuo. Purification via flash chromatography (95:5 CH2Cl2) afforded 5-[4,5-dimethoxy-2-(1-methyl-2-phenyl-ethyl)-benzyl]-pyrimidine-2,4-diamine (0.066 g, 58%) as a white foam; melting point (HCl salt) 227.1-227-4° C.

Workup

  1. temperaturewas warmed to reflux
  2. customquenched by the Fieser method
  3. filtrationAfter 30 min the mixture was filtered through a pad of celite
  4. concentrationconcentrated in vacuo
  5. customto give a crude white solid
  6. additionas added
  7. extractionthe mixture was extracted with ethyl acetate
  8. washwashed with brine
  9. dry with materialThe combined organics were dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customPurification via flash chromatography (95:5 CH2Cl2)

Sources & evidence

ORD record
ord-3fe08ed062bf44268f489c2254b7bf6a
Source dataset
uspto-grants-2011_08
Patent number
US08008313B2

Reaction notes

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