Guanidine → Trimethoprim

HRID 614280

Reaction equation

HRID 614280 reaction equation
C(OC(OCC)[C:5]([CH:21]=O)([CH2:8][C:9]1[CH:14]=[C:13]([O:15][CH3:16])[C:12]([O:17][CH3:18])=[C:11]([O:19][CH3:20])[CH:10]=1)[C:6]#[N:7])C.[NH2:26][C:27]([NH2:29])=[NH:28]>C(O)C>[NH2:29][C:27]1[N:28]=[C:6]([NH2:7])[C:5]([CH2:8][C:9]2[CH:14]=[C:13]([O:15][CH3:16])[C:12]([O:17][CH3:18])=[C:11]([O:19][CH3:20])[CH:10]=2)=[CH:21][N:26]=1

Participants

4

Reactant 2

HCID 3520GuanidineHCID 12559125alpha-Diethoxymethyl-alpha-formyl-beta-(3,4,5-trimethoxyphenyl) propionitrile

Product 1

HCID 5578TrimethoprimYield 67.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

α-Diethoxymethyl-α-formyl-β-(3,4,5-trimethoxyphenyl) propionitrile (35.1 g, 0.10 mol) was added to an ethanolic solution of guanidine (from 0.35 mol of guanidine hydrochloride). The mixture was heated at reflux for a total of 6.5 hours during which time enough ethanol was allowed to boil off to bring the reaction temperature up to 85°. The dark solution was allowed to cool and stand overnight. The mixture was filtered, and the solid was washed with cold ethanol and dried to yield crude product (24.4 g, 84.1%). Purification was effected by dissolving the crude product in hot aqueous acetic acid and reprecipitation with concentrated ammonium hydroxide. The precipitate was washed twice with water, once with cold acetone, and dried to yield 2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine (19.5 g, 67.2%), m.p. 197°-198° C. (identity confirmed by nmr). The acetone was concentrated in vacuo to dryness yielding additional though somewhat less pure trimethoprim (2,5 g, 8.6%, m.p. 194°-196° C.).

Workup

  1. temperatureThe mixture was heated
  2. customup to 85°
  3. temperatureto cool
  4. filtrationThe mixture was filtered
  5. washthe solid was washed with cold ethanol
  6. customdried
  7. customto yield crude product (24.4 g, 84.1%)
  8. customPurification
  9. dissolutionby dissolving
  10. customthe crude product in hot aqueous acetic acid and reprecipitation with concentrated ammonium hydroxide
  11. washThe precipitate was washed twice with water, once with cold acetone
  12. customdried

Sources & evidence

ORD record
ord-ed68d8e212dc4b5499be1cf8e5adaa6b
Source dataset
uspto-grants-1979_03
Patent number
US04144263

Linked notes

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