3-Hydroxy-2,2-dimethylpropionic acid → HCID 67521455, compound

HRID 1787048Notes

Reaction equation

HRID 1787048 reaction equation
Cl.Cl.[NH2:3][CH2:4][CH2:5][N:6]1[C:14]2[C:13]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=4)=[C:18]([Cl:33])[CH:17]=3)=[N:12][CH:11]=[N:10][C:9]=2[CH:8]=[CH:7]1.[OH:34][CH2:35][C:36]([CH3:41])([CH3:40])[C:37](O)=[O:38].Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1>CN(C)C=O.O.C(N(CC)CC)C>[ClH:33].[Cl:33][C:18]1[CH:17]=[C:16]([NH:15][C:13]2[C:14]3[N:6]([CH2:5][CH2:4][NH:3][C:35](=[O:34])[C:36]([CH3:41])([CH3:40])[CH2:37][OH:38])[CH:7]=[CH:8][C:9]=3[N:10]=[CH:11][N:12]=2)[CH:21]=[CH:20][C:19]=1[O:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=1

Participants

8

Reactant 4

HCID 785483-Hydroxy-2,2-dimethylpropionic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 568513565-(2-aminoethyl)-N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidin-4-amine dihydrochloride

Product 1

HCID 67521455HCID 67521455, compoundYield 141.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

A solution of 5-(2-aminoethyl)-N-{3-chloro-4-[3-(trifluoromethyl)phenoxy]phenyl}-5H-pyrrolo[3,2-d]pyrimidin-4-amine dihydrochloride (150 mg), 3-hydroxy-2,2-dimethylpropanoic acid (68 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (166 mg), 1-hydroxybenzotriazole monohydrate (132 mg) and triethylamine (0.40 mL) in N,N-dimethylformamide (5.0 mL) was stirred at room temperature for 20 hrs. Water was added to the reaction system and the mixture was extracted with ethyl acetate. The organic layer washed with water and saturated brine and dried over magnesium sulfate. After concentration under reduced pressure, the residue was separated and purified by basic silica gel column chromatography (eluent, ethyl acetate→methanol:ethyl acetate=15:85). After concentration under reduced pressure, ethyl acetate (2.0 mL) and 4N hydrochloric acid/ethyl acetate (0.5 mL) were added, and the mixture was stirred at room temperature for 15 hrs. After concentration under reduced pressure, the precipitated crystals were collected by filtration. To a solution of the collected crystals in ethanol (2.0 mL) was added 1N aqueous sodium hydroxide solution at room temperature, and the mixture was stirred for 2 days. The mixture was concentrated under reduced pressure and a solution of the residue in ethyl acetate was washed with water and saturated brine and dried over magnesium sulfate. After concentration under reduced pressure, 4N hydrochloric acid/ethyl acetate (0.5 mL) was added to a solution of the residue in ethyl acetate (1.0 mL). After concentration under reduced pressure, the precipitated crystals were collected by filtration. The crystals were washed with diisopropyl ether to give the title compound (119 mg) as colorless crystals.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer washed with water and saturated brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationAfter concentration under reduced pressure
  5. customthe residue was separated
  6. custompurified by basic silica gel column chromatography (eluent, ethyl acetate→methanol:ethyl acetate=15:85)
  7. concentrationAfter concentration under reduced pressure, ethyl acetate (2.0 mL) and 4N hydrochloric acid/ethyl acetate (0.5 mL)
  8. additionwere added
  9. concentrationAfter concentration under reduced pressure
  10. filtrationthe precipitated crystals were collected by filtration
  11. additionTo a solution of the collected crystals in ethanol (2.0 mL) was added 1N aqueous sodium hydroxide solution at room temperature
  12. stirringthe mixture was stirred for 2 days
  13. concentrationThe mixture was concentrated under reduced pressure
  14. washa solution of the residue in ethyl acetate was washed with water and saturated brine
  15. dry with materialdried over magnesium sulfate
  16. concentrationAfter concentration under reduced pressure, 4N hydrochloric acid/ethyl acetate (0.5 mL)
  17. additionwas added to a solution of the residue in ethyl acetate (1.0 mL)
  18. concentrationAfter concentration under reduced pressure
  19. filtrationthe precipitated crystals were collected by filtration
  20. washThe crystals were washed with diisopropyl ether

Sources & evidence

ORD record
ord-79d8f9174b804d84b1fa5b73fbf2f019
Source dataset
uspto-grants-2009_03
Patent number
US07507740B2

Reaction notes

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