Water → HCID 54377278, compound

HRID 275887Notes

Reaction equation

HRID 275887 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:20][C:21]([OH:23])=O)[CH:6]=[CH:7][C:8]=1[NH:9][C:10]([NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:19])=[O:11].F[P-](F)(F)(F)(F)F.N1([O:40][C:41](N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[OH2:57].[CH3:58][N:59]([CH3:62])C=O>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:20][C:21]([N:59]([CH2:58][C:41]([OH:40])=[O:57])[CH3:62])=[O:23])[CH:6]=[CH:7][C:8]=1[NH:9][C:10]([NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:19])=[O:11]

Participants

6

Reactant 5

HCID 962WaterHCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 114498403-Methoxy-4-o-tolylureidophenylacetic acid

Product 1

HCID 54377278HCID 54377278, compound

Procedure

A solution of [3-methoxy-4-(3-o-tolylureido)phenyl]-acetic acid (2.50 g, Reference Example 5) and sareosine ethyl ester hydrochloride(1.23 g) in dimethylformamide (75 ml) was treated with [O-(7-azabenzotriazol-1-yl)-1,1,3,3,-tetramethyluronium hexafluorophosphate] (3.03 g) and diisopropylethylamine (430 ml). The reaction mixture was stirred at room temperature for 2 hours, then treated with water (200 ml) and then filtered. The white solid was suspended in tetrahydrofuran (100 ml) and the mixture was then treated with lithium hydroxide hydrate (0.45 g) in water (20 ml). After stirring for 45 minutes the mixture was concentrated to remove the tetrahydrofuran. The remaining aqueous phase was washed with ethyl acetate then acidified by addition of hydrochloric acid (1M), then extracted three times with ethyl acetate. The combined organic extracts were washed with brine, then dried over magnesium sulphate and then evaporated to yield the title compound (2.24 g) as a white solid, m. p. 125-130° C. (with decomposition). HPLC: RT=10.83 minutes (gradient elution using a mixture of acetonitrile and water 1:4 to 4:1 v/v). MS(-ve) [M−1]−384.

Workup

  1. filtrationfiltered
  2. additionthe mixture was then treated with lithium hydroxide hydrate (0.45 g) in water (20 ml)
  3. stirringAfter stirring for 45 minutes the mixture
  4. concentrationwas concentrated
  5. customto remove the tetrahydrofuran
  6. washThe remaining aqueous phase was washed with ethyl acetate
  7. additionthen acidified by addition of hydrochloric acid (1M)
  8. extractionextracted three times with ethyl acetate
  9. washThe combined organic extracts were washed with brine
  10. dry with materialdried over magnesium sulphate
  11. customevaporated

Sources & evidence

ORD record
ord-6e3a26c9b919456ca49a803eef2f95ba
Source dataset
uspto-grants-2002_03
Patent number
US06352977B1

Reaction notes

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