Trifluoroacetic acid → (2-(2-Amino-3-morpholinoquinolin-6-yl)-3-methylphenyl)(pyrrolidin-1-yl)methanone

HRID 1028937Notes

Reaction equation

HRID 1028937 reaction equation
COC1C=CC(C[NH:8][C:9]2[C:18]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)=[CH:17][C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:25]4[C:30]([CH3:31])=[CH:29][CH:28]=[CH:27][C:26]=4[C:32]([N:34]4[CH2:38][CH2:37][CH2:36][CH2:35]4)=[O:33])[CH:15]=3)[N:10]=2)=CC=1.C(O)(C(F)(F)F)=O>>[NH2:8][C:9]1[C:18]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)=[CH:17][C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:25]3[C:30]([CH3:31])=[CH:29][CH:28]=[CH:27][C:26]=3[C:32]([N:34]3[CH2:35][CH2:36][CH2:37][CH2:38]3)=[O:33])[CH:15]=2)[N:10]=1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 71253303(2-(2-(4-Methoxybenzylamino)-3-morpholinoquinolin-6-yl)-3-methylphenyl)(pyrrolidin-1-yl)methanone

Product 1

HCID 53328455(2-(2-Amino-3-morpholinoquinolin-6-yl)-3-methylphenyl)(pyrrolidin-1-yl)methanone

Procedure

A solution of (2-(2-(4-methoxybenzylamino)-3-morpholinoquinolin-6-yl)-3-methylphenyl)(pyrrolidin-1-yl)methanone (30 mg, 0.056 mmol) and TFA (2 mL) was heated at 90° C. After 3 h, the reaction mixture was concentrated in vacuo, diluted with DCM and concentrated again. The crude product was dissolved in MeOH and filtered through an SCX (1 g) column then eluted with a 2M ammonia methanol solution to release the product. This filtrate was concentrated in vacuo to give a light orange solid that was washed with ether and decanted to remove most of the remaining starting material. The remaining solid was dissolved in DCM and purified by preparative thin layer chromatography (5×20 cm, 1000 um, 10% MeOH:DCM) to give (2-(2-amino-3-morpholinoquinolin-6-yl)-3-methylphenyl)(pyrrolidin-1-yl)methanone as a white solid. MS (ESI, pos. ion) m/z: 417 (M+1).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. additiondiluted with DCM
  3. concentrationconcentrated again
  4. dissolutionThe crude product was dissolved in MeOH
  5. filtrationfiltered through an SCX (1 g) column
  6. washthen eluted with a 2M ammonia methanol solution
  7. concentrationThis filtrate was concentrated in vacuo
  8. customto give a light orange solid
  9. washthat was washed with ether
  10. customdecanted
  11. customto remove most of the
  12. dissolutionThe remaining solid was dissolved in DCM
  13. custompurified by preparative thin layer chromatography (5×20 cm, 1000 um, 10% MeOH:DCM)

Sources & evidence

ORD record
ord-2f90e7cb395a4f25b5c3a7d8accb77da
Source dataset
uspto-grants-2014_05
Patent number
US08735384B2

Reaction notes

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