N,N-Dimethylglycine → N-(4-((1-(2-fluorobenzyl)-3-(cyclopropylmethyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)methyl)phenyl)-2-(dimethylamino)acetamide

HRID 720647Notes

Reaction equation

HRID 720647 reaction equation
[NH2:1][C:2]1[CH:31]=[CH:30][C:5]([CH2:6][C:7]2[NH:15][C:14]3[C:13](=[O:16])[N:12]([CH2:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=4[F:24])[C:11](=[O:25])[N:10]([CH2:26][CH:27]4[CH2:29][CH2:28]4)[C:9]=3[N:8]=2)=[CH:4][CH:3]=1.[CH3:32][N:33]([CH2:35][C:36](O)=[O:37])[CH3:34].C(N(CC)C(C)C)(C)C>CN(C)C=O>[CH:27]1([CH2:26][N:10]2[C:9]3[N:8]=[C:7]([CH2:6][C:5]4[CH:4]=[CH:3][C:2]([NH:1][C:36](=[O:37])[CH2:35][N:33]([CH3:34])[CH3:32])=[CH:31][CH:30]=4)[NH:15][C:14]=3[C:13](=[O:16])[N:12]([CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[F:24])[C:11]2=[O:25])[CH2:28][CH2:29]1

Participants

5

Reactant 3

HCID 673N,N-DimethylglycineHCID 81531DiisopropylethylamineHCID 218917373-Cyclopropylmethyl-8-[4-aminobenzyl]-1-(2-fluorobenzyl)-3,7-dihydro-purine-2,6-dione

Product 1

HCID 10483960N-(4-((1-(2-fluorobenzyl)-3-(cyclopropylmethyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)methyl)phenyl)-2-(dimethylamino)acetamideYield 44.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 8-(4-amino-benzyl)-3-cyclopropylmethyl-1-(2-fluoro-benzyl)-3,7-dihydro-purine-2,6-dione (45 mg, 0.11 mmol) in N,N-dimethylformamide (1.0 mL) at 25° C. was treated with dimethylamino-acetic acid (11 mg, 0.11 mmol), O-benzotriazol-1-yl-N,N.N′N′-tetramethyluronium hexafluorophosphate (45 mg, 0.12 mmol), and N,N-diisopropylethylamine (56 μL, 0.32 mmol). The resulting solution was stirred at 25° C. for 48 h. At this time, the reaction was concentrated in vacuo. The residue was dissolved in chloroform and then was washed with a saturated aqueous sodium chloride solution (1×10 mL). The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting residue was purified by HPLC (15–60% acetonitrile/water/0.075% trifluoroacetic acid over 30 min). Fractions with the desired product were combined and concentrated in vacuo. The resulting residue was diluted with dichloromethane (100 mL) and was washed with a saturated aqueous sodium bicarbonate solution (25 mL). The aqueous layer was re-extracted with dichloromethane (1×50 mL). The combined organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting solid was dried in vacuo for 24 h to afford N-{4-[3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-2-dimethylamino-acetamide (24 mg, 44.3%) as an off-white solid: LR-MS for C27H29FN6O3 (M+H)+ at m/z=505.

Workup

  1. concentrationAt this time, the reaction was concentrated in vacuo
  2. dissolutionThe residue was dissolved in chloroform
  3. washwas washed with a saturated aqueous sodium chloride solution (1×10 mL)
  4. dry with materialThe organics were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by HPLC (15–60% acetonitrile/water/0.075% trifluoroacetic acid over 30 min)
  8. concentrationconcentrated in vacuo
  9. additionThe resulting residue was diluted with dichloromethane (100 mL)
  10. washwas washed with a saturated aqueous sodium bicarbonate solution (25 mL)
  11. extractionThe aqueous layer was re-extracted with dichloromethane (1×50 mL)
  12. dry with materialThe combined organics were dried over magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customThe resulting solid was dried in vacuo for 24 h

Sources & evidence

ORD record
ord-d002131f361546e9ab153a1fd992ef54
Source dataset
uspto-grants-2006_11
Patent number
US07135475B2

Reaction notes

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