Hydrochloric Acid → 2,6-Diamino-4-[4-(2,2,2-trifluoro-acetamidomethyl)-benzyloxy]-pyrimidine

HRID 1695089Notes

Reaction equation

HRID 1695089 reaction equation
[OH:1][CH2:2][C:3]1[CH:16]=[CH:15][C:6]([CH2:7][NH:8][C:9](=[O:14])[C:10]([F:13])([F:12])[F:11])=[CH:5][CH:4]=1.[H-].[Na+].[NH2:19][C:20]1[N:25]=[C:24](Cl)[CH:23]=[C:22]([NH2:27])[N:21]=1.Cl>CS(C)=O>[NH2:19][C:20]1[N:25]=[C:24]([O:1][CH2:2][C:3]2[CH:4]=[CH:5][C:6]([CH2:7][NH:8][C:9](=[O:14])[C:10]([F:12])([F:13])[F:11])=[CH:15][CH:16]=2)[CH:23]=[C:22]([NH2:27])[N:21]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 674322,4-Diamino-6-chloropyrimidineHCID 15852209N-(4-Hydroxymethylbenzyl)trifluoroacetamide

Product 1

HCID 457894072,6-Diamino-4-[4-(2,2,2-trifluoro-acetamidomethyl)-benzyloxy]-pyrimidineYield 27%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

N-(4-Hydroxymethyl-benzyl)-2,2,2-trifluoro-acetamide (12.0 g, 52 mmol) is dissolved in 80 ml dry DMSO, and NaH (4.08 g, 102 mmol, suspension 60% in mineral oil) is added in portions over 30 min under an argon atmosphere. After stirring at room temperature for 1 h, 2,6-diamino-4-chloropyrimidine (7.52 g, 52 mmol) is added and the reaction mixture heated to 60° C. over night. After cooling to room temperature, the mixture is poured into 1 L of 1 N HCl, and the product extracted with ethyl acetate (500 mL). The combined organic phases are washed with water and brine, dried over MgSO4, and the solvent evaporated. The residue is purified by flash column chromatography (ethyl acetate/methanol 100:0 to 80:20) to yield the title compound as a colorless solid (4.7 g, 13.78 mmol, 27%). 1H-NMR (400 MHz, DMSO-d6): δ=9.99 (t, J=6.1, 1H, CONH), 7.34 (d, J=8.1, 2H, ArH), 7.26 (d, J=8.1, 2H, ArH), 6.02 (s br, 2H, NH2), 5.89 (s br, 2H, NH2), 5.16 (s, 2H, OCH2), 5.01 (s, 1H, 4-H), 4.36 (d, J=6.1, 2H, CH2NCO) ppm.

Workup

  1. temperaturethe reaction mixture heated to 60° C. over night
  2. temperatureAfter cooling to room temperature
  3. extractionthe product extracted with ethyl acetate (500 mL)
  4. washThe combined organic phases are washed with water and brine
  5. dry with materialdried over MgSO4
  6. customthe solvent evaporated
  7. customThe residue is purified by flash column chromatography (ethyl acetate/methanol 100:0 to 80:20)

Sources & evidence

ORD record
ord-e003e2fc961a4b17bf1e7294430dd850
Source dataset
uspto-grants-2012_04
Patent number
US08163479B2

Reaction notes

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