Triphenylphosphine → HCID 25159011, compound

HRID 1714843Notes

Reaction equation

HRID 1714843 reaction equation
[NH2:1][C:2]1[N:11]=[CH:10][C:9]2[NH:8][C:7](=[O:12])[C@@H:6]([CH3:13])[N:5]([CH2:14][C:15]3[C:20]([CH3:21])=[C:19]([O:22][CH3:23])[C:18]([CH3:24])=[CH:17][N:16]=3)[C:4]=2[N:3]=1.[CH3:25][O:26][CH2:27][CH2:28][CH2:29]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1.CO.C(Cl)Cl>[NH2:1][C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH2:29][CH2:28][CH2:27][O:26][CH3:25])[C:7](=[O:12])[C@@H:6]([CH3:13])[N:5]([CH2:14][C:15]3[C:20]([CH3:21])=[C:19]([O:22][CH3:23])[C:18]([CH3:24])=[CH:17][N:16]=3)[C:4]=2[N:3]=1

Participants

8

Reactant 4

HCID 11776Triphenylphosphine3×HCID 741163-Methoxy-1-propanolHCID 5363146Diisopropyl azodicarboxylate3×HCID 25158234HCID 25158234, compound

Product 1

HCID 25159011HCID 25159011, compoundYield 27.7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

(7R)-2-Amino-8-[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]-7-methyl-7,8-dihydropteridin-6(5H)-one (Example 2[2])(60 mg, 0.18 mmol) was suspended in THF (10 mL) and the 3-methoxy-1-propanol (70 μL, 0.73 mmol) was added, followed by triphenylphosphine (192 mg, 0.73 mmol) and DIAD (144 μL, 0.73 mmol). The mixture was stirred at room temperature for 2 hours. A further quantity of triphenylphosphine (192 mg, 0.73 mmol) and DIAD (144 μL, 0.73 mmol) were added and stirring continued for 2 hours. A further quantity of triphenylphosphine (192 mg, 0.73 mmol) and DIAD (144 μL, 0.73 mmol) were added and stirring continued overnight. TLC and LCMS analysis showed complete reaction; the mixture was diluted with methanol (5 mL) and loaded onto an SCX-2 column which had been equilibrated with 30% methanol in DCM. The column was eluted with 30% methanol in DCM to remove impurities, then with 30% (3M NH3 in methanol) in DCM to elute the product. The appropriate fractions were concentrated in vacuo; the residue (about 40 mg) was found to be a mixture of N- and O-alkylated products. The sample was dissolved in methanol (5 mL) and 6N HCl (2 mL) was added. The mixture was stirred at room temperature for 2 hours. LCMS showed complete hydrolysis of the O-alkylated material; the desired N-alkylated material was unchanged. The mixture was concentrated in vacuo and the residue was purified by chromatography, eluting with 0 to 5% (10:1 methanol/concentrated NH3 (aqueous)) in DCM. The appropriate fractions were concentrated under reduced pressure to give the title compound as a pale yellow gum (20 mg, 27%); 1H NMR spectrum (400 MHz, CDCl3) δ 1.36 (3H, d), 1.89 (2H, ddt), 2.17 (3H, s), 2.25 (3H, s), 3.39 (2H, td), 3.75 (3H, s), 3.81 (1H, dd), 3.97 (1H, dd), 4.03 (1H, q), 4.09 (1H, d), 4.67 (2H, s), 5.70 (1H, d), 7.70 (1H, s), 8.18 (1H, s); Mass spectrum: (M+H) 401.

Workup

  1. stirringstirring
  2. waitcontinued for 2 hours
  3. stirringstirring continued overnight
  4. customreaction
  5. washThe column was eluted with 30% methanol in DCM
  6. customto remove impurities
  7. washwith 30% (3M NH3 in methanol) in DCM to elute the product
  8. concentrationThe appropriate fractions were concentrated in vacuo
  9. additiona mixture of N- and O-alkylated products
  10. dissolutionThe sample was dissolved in methanol (5 mL)
  11. addition6N HCl (2 mL) was added
  12. stirringThe mixture was stirred at room temperature for 2 hours
  13. customhydrolysis of the O-alkylated material
  14. concentrationThe mixture was concentrated in vacuo
  15. customthe residue was purified by chromatography
  16. washeluting with 0 to 5% (10:1 methanol/concentrated NH3 (aqueous)) in DCM
  17. concentrationThe appropriate fractions were concentrated under reduced pressure

Sources & evidence

ORD record
ord-a470b4efcae04716bf19e569569c05a0
Source dataset
uspto-grants-2010_09
Patent number
US07799781B2

Reaction notes

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