(S)-1-(2,4-Difluorophenyl)ethanamine → HCID 58268930, compound

HRID 1428185Notes

Reaction equation

HRID 1428185 reaction equation
Cl[C:2]1[N:7]=[C:6]([S:8][CH3:9])[N:5]=[C:4]([C:10]2[CH:11]([NH2:19])[NH:12][N:13]3[CH:18]=[CH:17][CH:16]=[N:15][C:14]=23)[CH:3]=1.[F:20][C:21]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=1[C@@H:28]([NH2:30])[CH3:29]>CN1C(=O)CCC1>[F:20][C:21]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:22]=1[C@@H:28]([NH:30][C:2]1[N:7]=[C:6]([S:8][CH3:9])[N:5]=[C:4]([C:10]2[C:11]([NH2:19])=[N:12][N:13]3[CH:18]=[CH:17][CH:16]=[N:15][C:14]=23)[CH:3]=1)[CH3:29]

Participants

4

Reactant 2

HCID 2060581(S)-1-(2,4-Difluorophenyl)ethanamineHCID 86653540HCID 86653540, compound

Product 1

HCID 58268930HCID 58268930, compoundYield 19.4%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
220 °C

Procedure

3-(6-Chloro-2-(methylthio)pyrimidin-4-yl)-1,2-dihydropyrazolo[1,5-a]pyrimidin-2-amine (4b) (500 mg, 1.70 mmoles) was dissolved in 5 mL of NMP along with (S)-1-(2,4 difluorophenyl)-ethylamine (988 mg, 5.0 mmoles, added as the free base). The reaction mixture was heated in the microwave three times at 220° C., for 15 minutes each. The reaction progress was monitored by LC/MS. Upon completion, the reaction was quenched by addition of 1N HCl to the vigorously stirred material until a thick oily material separated. This crude mixture was centrifuged and the thick oil separated. The oily mass was transferred to a round-bottomed flask and methanol was added. Solvents were removed under reduced pressure and the resulting solid was suspended in acetonitrile, warmed to 50° C. and vigorously stirred. Then it was cooled and the resulting precipitate was suction-filtered. The filtrate was reduced to an oil under reduced pressure and then re-dissolved in a minimum amount of methanol and purified via HPLC on C18 silica with acetonitrile/water/TFA as the eluent. After lyophilizing the desired fractions a beige solid was obtained (136 mg, 19.4% yield).

Workup

  1. additionadded as the free base)
  2. customUpon completion, the reaction was quenched by addition of 1N HCl to the vigorously stirred material until a thick oily material
  3. customseparated
  4. customthe thick oil separated
  5. customThe oily mass was transferred to a round-bottomed flask
  6. additionmethanol was added
  7. customSolvents were removed under reduced pressure
  8. temperaturewarmed to 50° C.
  9. temperatureThen it was cooled
  10. filtrationthe resulting precipitate was suction-filtered
  11. dissolutionre-dissolved in a minimum amount of methanol
  12. custompurified via HPLC on C18 silica with acetonitrile/water/TFA as the eluent
  13. customwas obtained (136 mg, 19.4% yield)

Sources & evidence

ORD record
ord-c142ae33d4224345a7f2ee94b5b5be84
Source dataset
uspto-grants-2015_01
Patent number
US08937064B2

Reaction notes

Loading…