Trifluoroacetic acid → 2-(2-(2-(5-Chloro-2-(1-(piperidin-4-yl)-1H-pyrazol-4-ylamino)pyrimidin-4-yl)ethyl)phenyl)propanamide

HRID 592425Notes

Reaction equation

HRID 592425 reaction equation
[NH2:1][C:2](=[O:39])[CH:3]([C:5]1[CH:38]=[CH:37][CH:36]=[CH:35][C:6]=1[CH2:7][CH2:8][C:9]1[C:14]([Cl:15])=[CH:13][N:12]=[C:11]([NH:16][C:17]2[CH:18]=[N:19][N:20]([CH:22]3[CH2:27][CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24][CH2:23]3)[CH:21]=2)[N:10]=1)[CH3:4].C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:15][C:14]1[C:9]([CH2:8][CH2:7][C:6]2[CH:35]=[CH:36][CH:37]=[CH:38][C:5]=2[CH:3]([CH3:4])[C:2]([NH2:1])=[O:39])=[N:10][C:11]([NH:16][C:17]2[CH:18]=[N:19][N:20]([CH:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)[CH:21]=2)=[N:12][CH:13]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86712309tert-Butyl 4-(4-(4-(2-(1-amino-1-oxopropan-2-yl)phenethyl)-5-chloropyrimidin-2-ylamino)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Product 1

HCID 732947842-(2-(2-(5-Chloro-2-(1-(piperidin-4-yl)-1H-pyrazol-4-ylamino)pyrimidin-4-yl)ethyl)phenyl)propanamideYield 26%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of tert-butyl 4-(4-(4-(2-(1-amino-1-oxopropan-2-yl)phenethyl)-5-chloropyrimidin-2-ylamino)-1H-pyrazol-1-yl)piperidine-1-carboxylate A32 (0.090 g, 0.162 mmol) in DCM (5 mL) was added TFA (2.0 mL) and the mixture was stirred at room temperature for 1.5 hours. The solvent was removed and the residue was suspended in EtOAc (5 mL) and washed with 1M HCl. The aqueous layer was basified with 1M NaOH and extracted with EtOAc (2×5 mL). The combined organic layers were dried (MgSO4), filtered and concentrated in vacuo to give a crude purple oil which was purified by flash chromatography (Combiflash Rf, 0-30% MeOH in DCM) to give the title compound 43 as a red oil (0.019 g, 26% yield). LCMS-C: rt 4.24 min; m/z 454 [M+H]+.

Workup

  1. customThe solvent was removed
  2. washwashed with 1M HCl
  3. extractionextracted with EtOAc (2×5 mL)
  4. dry with materialThe combined organic layers were dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give a crude purple oil which
  8. customwas purified by flash chromatography (Combiflash Rf, 0-30% MeOH in DCM)

Sources & evidence

ORD record
ord-40abdb4367ac43649476e2692da66e12
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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