Dimethylformamide → 1-(4-Fluorophenoxy)-3-[2-(1,3,5-trimethylpyrimidine-2,4-dion-6-ylamino)-ethylamino]-propan-2-ol hydrogen fumarate

HRID 365190

Reaction equation

HRID 365190 reaction equation
[CH2:1]([O:5][C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=1)[CH:2]1O[CH2:3]1.[NH2:13][CH2:14][CH2:15][NH:16][C:17]1[N:18]([CH3:27])[C:19](=[O:26])[N:20]([CH3:25])[C:21](=[O:24])[C:22]=1[CH3:23].CN(C)C=O.[C:33]([OH:40])(=[O:39])/[CH:34]=[CH:35]/[C:36]([OH:38])=[O:37]>C(O)C.C(OCC)(=O)C>[C:33]([OH:40])(=[O:39])/[CH:34]=[CH:35]/[C:36]([O:38][CH:2]([CH2:3][NH:13][CH2:14][CH2:15][NH:16][C:17]1[N:18]([CH3:27])[C:19](=[O:26])[N:20]([CH3:25])[C:21](=[O:24])[C:22]=1[CH3:23])[CH2:1][O:5][C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][CH:7]=1)=[O:37]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 444972Fumaric AcidHCID 27247922-[(4-Fluorophenoxy)methyl]oxiraneHCID 128188664-(2-aminoethylamino)-1,3,5-trimethylpyrimidine-2,6(1H,3H)-dione

Product 1

HCID 704540321-(4-Fluorophenoxy)-3-[2-(1,3,5-trimethylpyrimidine-2,4-dion-6-ylamino)-ethylamino]-propan-2-ol hydrogen fumarate

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

3.36 g. 4-Fluorophenyl glycidyl ether and 8.5 g. 4-(2-aminoethylamino)-1,3,5-trimethylpyrimidine-2,6-(1H,3H)-dione are dissolved in 10 ml. dimethylformamide and left to stand for 2 days at ambient temperature. The reaction mixture is then poured into 100 ml. water, extracted with methylene chloride, dried and evaporated. The viscous oil obtained is separated by column chromatography using silica gel and, as elution agent, methylene chloride-ammonia-saturated methanol (20:1 v/v). The product obtained by evaporation of the pure fractions is dissolved in 20 ml. ethyl acetate, whereafter 1.8 g. fumaric acid, dissolved in ethanol, is added thereto. After filtering off with suction, the crystalline product obtained is recrystallized from ethanol, with the addition of 0.9 g. fumaric acid and with the use of active charcoal. There are obtained 5.2 g. (52% of theory) of the desired product in the form of colorless crystals; m.p. 163°-167° C.

Workup

  1. additionThe reaction mixture is then poured into 100 ml
  2. extractionwater, extracted with methylene chloride
  3. customdried
  4. customevaporated
  5. customThe viscous oil obtained
  6. customis separated by column chromatography
  7. washas elution agent, methylene chloride-ammonia-saturated methanol (20:1 v/v)
  8. customThe product obtained by evaporation of the pure fractions
  9. dissolutionis dissolved in 20 ml
  10. additionis added
  11. filtrationAfter filtering off with suction
  12. customthe crystalline product obtained
  13. customis recrystallized from ethanol, with the addition of 0.9 g
  14. customThere are obtained 5.2 g

Sources & evidence

ORD record
ord-cec10090afb14f8d95a58242ddb2d449
Source dataset
uspto-grants-1986_08
Patent number
US04608383

Linked notes

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