1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 90402994, compound

HRID 2200579Notes

Reaction equation

HRID 2200579 reaction equation
[NH2:1][C:2]1[C:3](=[O:20])[N:4]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)[C:5](=[O:10])[N:6]([CH3:9])[C:7]=1[NH2:8].[F:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:31])[F:30])=[CH:24][C:23]=1[CH2:33][C:34](O)=O.CCN=C=NCCCN(C)C>C(O)C>[F:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][C:29]([F:30])([F:31])[F:32])=[CH:24][C:23]=1[CH2:33][C:34]1[NH:1][C:2]2[C:3](=[O:20])[N:4]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)[C:5](=[O:10])[N:6]([CH3:9])[C:7]=2[N:8]=1

Participants

5

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27833282-Fluoro-5-(trifluoromethoxy)benzeneacetic acidHCID 90402811HCID 90402811, compound2×

Product 1

HCID 90402994HCID 90402994, compoundYield 48.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a solution of 5,6-diamino-3-(4-methoxybenzyl)-1-methylpyrimidine-2,4(1H,3H)-dione (80 mg, 0.289 mmol, intermediate 59) in ethanol (2 mL) was added 2-(2-fluoro-5-(trifluoromethoxy)phenyl)acetic acid (68.8 mg, 0.289 mmol) followed by EDCI (66.5 mg, 0.347 mmol) and the mixture was stirred at room temperature for 2 h. The reaction was partitioned between ethyl acetate and brine. The organic phase was dried and concentrated. The residue was dissolved in ethanol (3 mL) and 1 mM sodium hydroxide (1 mL) was added. The resulting mixture was stirred at reflux for 3 h. The reaction was concentrated and residue was partitioned between ethyl acetate and brine. The organic layer was dried and concentrated to give a crude solid product, which was triturated with ethanol, collected and dried to afford 8-(2-fluoro-5-(trifluoromethoxy)benzyl)-1-(4-methoxybenzyl)-3-methyl-1H-purine-2,6(3H,7H)-dione (67 mg, 48.4% yield) as a light yellow solid. LCMS retention time 1.611 min; LCMS MH+ 479.

Workup

  1. customThe reaction was partitioned between ethyl acetate and brine
  2. customThe organic phase was dried
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in ethanol (3 mL)
  5. addition1 mM sodium hydroxide (1 mL) was added
  6. stirringThe resulting mixture was stirred
  7. temperatureat reflux for 3 h
  8. concentrationThe reaction was concentrated
  9. customresidue was partitioned between ethyl acetate and brine
  10. customThe organic layer was dried
  11. concentrationconcentrated
  12. customto give a crude solid product, which
  13. customwas triturated with ethanol
  14. customcollected
  15. customdried

Sources & evidence

ORD record
ord-8e370a73eb9c43f4ab7f3194f9789033
Source dataset
uspto-grants-2016_06
Patent number
US09359359B2

Reaction notes

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