Trifluoroacetic acid → 1-(2-(2-(5-Chloro-2-((4-(piperidin-4-yl)phenyl)amino)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

HRID 592380Notes

Reaction equation

HRID 592380 reaction equation
C(O)(C(F)(F)F)=O.[C:8]([C:11]1([C:14]2[CH:48]=[CH:47][CH:46]=[CH:45][C:15]=2[CH2:16][CH2:17][C:18]2[C:23]([Cl:24])=[CH:22][N:21]=[C:20]([NH:25][C:26]3[CH:31]=[CH:30][C:29]([CH:32]4[CH2:37][CH2:36][N:35](C(OC(C)(C)C)=O)[CH2:34][CH2:33]4)=[CH:28][CH:27]=3)[N:19]=2)[CH2:13][CH2:12]1)(=[O:10])[NH2:9].C([O-])([O-])=O.[Na+].[Na+].CCOC(C)=O>C(Cl)Cl.O>[Cl:24][C:23]1[C:18]([CH2:17][CH2:16][C:15]2[CH:45]=[CH:46][CH:47]=[CH:48][C:14]=2[C:11]2([C:8]([NH2:9])=[O:10])[CH2:12][CH2:13]2)=[N:19][C:20]([NH:25][C:26]2[CH:31]=[CH:30][C:29]([CH:32]3[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]3)=[CH:28][CH:27]=2)=[N:21][CH:22]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 86712296tert-Butyl 4-(4-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-chloropyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Product 1

HCID 867122971-(2-(2-(5-Chloro-2-((4-(piperidin-4-yl)phenyl)amino)pyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamideYield 55%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

TFA (1.0 mL) was added to a solution of tert-butyl 4-(4-((4-(2-(1-carbamoylcyclopropyl)phenethyl)-5-chloropyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (A15) (121 mg, 210 μmol) in DCM (5 mL) and the resulting mixture was stirred at room temperature for 16 hours. Saturated aqueous Na2CO3 was added until the solution was basic then EtOAc (50 mL) and water (50 mL) were added. The organic layer was separated, washed with brine (20 mL), dried over MgSO4 then the volatiles removed in vacuo. The resulting residue was adsorbed onto silica gel and the resulting material washed with MeOH (300 mL) then 1 M NH3 in MeOH/EtOH (1:1) (300 mL). The volatiles from the ammoniacal washing were removed in vacuo and the resultant gum sonicated in Et2O (20 mL) to give a precipitate that was collected by filtration. Air drying of the filter cake gave the product 7 as a white solid (55 mg, 55%); 1H NMR (400 MHz, CDCl3) δ 8.28 (s, 1H), 7.52-7.46 (d, J=8.6 Hz, 2H), 7.46-7.41 (d, J=7.3 Hz, 1H), 7.37-7.32 (d, J=5.0 Hz, 2H), 7.31-7.25 (m, 2H, obscured), 7.23-7.18 (d, J=8.5 Hz, 2H), 7.15 (s, 1H), 5.33 (s, 2H), 3.34-3.12 (m, 6H), 2.84-2.71 (td, J=12.2, 2.3 Hz, 2H), 2.71-2.56 (tt, J=12.1, 3.7 Hz, 1H), 1.92-1.59 (m, 6H, obscured), 1.15 (s, 2H). LCMS-A: rt 4.527 min; m/z 477 [M+H]+.

Workup

  1. customThe organic layer was separated
  2. washwashed with brine (20 mL)
  3. dry with materialdried over MgSO4
  4. customthe volatiles removed in vacuo
  5. washthe resulting material washed with MeOH (300 mL)
  6. washThe volatiles from the ammoniacal washing
  7. customwere removed in vacuo
  8. customthe resultant gum sonicated in Et2O (20 mL)
  9. customto give a precipitate that
  10. filtrationwas collected by filtration
  11. customAir drying of the filter cake

Sources & evidence

ORD record
ord-2524ca3058134ebca33dd573a808de13
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

Loading…