Hydrochloric Acid → HCID 86615784, compound

HRID 1926137Notes

Reaction equation

HRID 1926137 reaction equation
[Cl:1][C:2]1[C:3]2[N:10]([CH2:11][CH:12]([NH:14]C(=O)OC(C)(C)C)[CH3:13])[CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[O:30][C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:40])([F:39])[F:38])[CH:32]=1)[NH2:26].C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.Cl>CN1CCCC1=O.O1CCCC1.O.C(N(CC)CC)C>[ClH:1].[ClH:22].[NH2:14][CH:12]([CH3:13])[CH2:11][N:10]1[C:3]2[C:2]([NH:26][C:25]3[CH:27]=[CH:28][C:29]([O:30][C:31]4[CH:36]=[CH:35][CH:34]=[C:33]([C:37]([F:38])([F:39])[F:40])[CH:32]=4)=[C:23]([Cl:22])[CH:24]=3)=[N:7][CH:6]=[N:5][C:4]=2[CH:8]=[CH:9]1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 90495Di-tert-butyl dicarbonateHCID 196269843-Chloro-4-[3-(trifluoromethyl)phenoxy]anilineHCID 86626255HCID 86626255, compound

Product 1

HCID 86615784HCID 86615784, compoundYield 57.2%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of tert-butyl [2-(4-chloro-5H-pyrrolo[3,2-d]pyrimidin-5-yl)-1-methylethyl]carbamate (350 mg) and 3-chloro-4-[3-(trifluoromethyl)phenoxy]aniline (423 mg) in 1-methyl-2-pyrrolidone (3.5 mL) was stirred at 120° C. for 4 hrs. After cooling to room temperature, triethylamine (0.24 mL) and di-tert-butyl dicarbonate (0.13 mL) were added, and the mixture was stirred for 20 hrs. Water was added to the reaction system and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried over magnesium sulfate. The residue was separated and purified by silica gel column chromatography (hexane:ethyl acetate=19:1→3:2→ethyl acetate) to give a brown solid. To a solution of the obtained solid in tetrahydrofuran (20 mL) was added 2N hydrochloric acid (10 mL) at room temperature, and the mixture was stirred at 60° C. for 20 hrs. After concentration under reduced pressure, ethanol was added and the mixture was further concentrated. To the residue was added diisopropyl ether, and the precipitated crystals were collected by filtration. The crystals were washed with diisopropyl ether to give the title compound (225 mg) as pale-yellow crystals.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with water and saturated brine
  3. dry with materialdried over magnesium sulfate
  4. customThe residue was separated
  5. custompurified by silica gel column chromatography (hexane:ethyl acetate=19:1→3:2→ethyl acetate)
  6. customto give a brown solid
  7. stirringthe mixture was stirred at 60° C. for 20 hrs
  8. concentrationAfter concentration under reduced pressure, ethanol
  9. additionwas added
  10. concentrationthe mixture was further concentrated
  11. additionTo the residue was added diisopropyl ether
  12. filtrationthe precipitated crystals were collected by filtration
  13. washThe crystals were washed with diisopropyl ether

Sources & evidence

ORD record
ord-a507784e1644407d881575dd0ebadf42
Source dataset
uspto-grants-2012_05
Patent number
US08178543B2

Reaction notes

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