1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → tert-Butyl 4-(4-((4-(2-(1-amino-1-oxopropan-2-yl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

HRID 1473069Notes

Reaction equation

HRID 1473069 reaction equation
O[N:2]1C2C=CC=CC=2N=N1.CCN=C=NCCCN(C)C.C(N(CC)C(C)C)(C)C.[C:31]([O:35][C:36]([N:38]1[CH2:43][CH2:42][CH:41]([C:44]2[CH:49]=[CH:48][C:47]([NH:50][C:51]3[N:56]=[C:55]([CH2:57][CH2:58][C:59]4[CH:64]=[CH:63][CH:62]=[CH:61][C:60]=4[CH:65]([CH3:69])[C:66]([O-])=[O:67])[C:54]([C:70]([F:73])([F:72])[F:71])=[CH:53][N:52]=3)=[CH:46][CH:45]=2)[CH2:40][CH2:39]1)=[O:37])([CH3:34])([CH3:33])[CH3:32].[Li+].C(=O)([O-])[O-].[NH4+].[NH4+]>C1COCC1.CN(C=O)C>[NH2:2][C:66](=[O:67])[CH:65]([C:60]1[CH:61]=[CH:62][CH:63]=[CH:64][C:59]=1[CH2:58][CH2:57][C:55]1[C:54]([C:70]([F:72])([F:73])[F:71])=[CH:53][N:52]=[C:51]([NH:50][C:47]2[CH:48]=[CH:49][C:44]([CH:41]3[CH2:42][CH2:43][N:38]([C:36]([O:35][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:37])[CH2:39][CH2:40]3)=[CH:45][CH:46]=2)[N:56]=1)[CH3:69]

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 517111Ammonium CarbonateHCID 71208836Lithium 2-(2-(2-(2-((4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)propanoate

Product 1

HCID 68283002tert-Butyl 4-(4-((4-(2-(1-amino-1-oxopropan-2-yl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

1-Hydroxybenzotriazole (21.1 mg, 0.156 mmol), EDCI (30.0 mg, 0.156 mmol) and N,N-diisopropylethylamine (54.5 μL, 0.313 mmol) were added to a solution of lithium 2-(2-(2-(2-((4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)propanoate (I54) (0.086 g, 0.142 mmol) in dry THF (6 mL) and dry DMF (1 mL) under an atmosphere of nitrogen. Ammonium carbonate (54.6 mg, 0.569 mmol) was added in one portion to the stirred reaction mixture after 10 minutes. The reaction was left stirred at room temperature for 18 hours. The volatiles were removed in vacuo and the residual solution was diluted with EtOAc (50 mL) then washed with saturated NaHCO3 (50 mL). The aqueous layer was extracted with EtOAc (2×50 mL). The combined organic layers were washed with water (50 mL) and brine (50 mL) and dried over Na2SO4. After filtration the solvent was removed in vacuo to afford a pale yellow solid. The crude material was purified by column chromatography on silica gel (0-85% EtOAc in petroleum benzine 40-60° C.) to afford the title compound (I55) (65.2 mg, 77%) as a white foamy solid;

Workup

  1. waitThe reaction was left
  2. customThe volatiles were removed in vacuo
  3. additionthe residual solution was diluted with EtOAc (50 mL)
  4. washthen washed with saturated NaHCO3 (50 mL)
  5. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
  6. washThe combined organic layers were washed with water (50 mL) and brine (50 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationAfter filtration the solvent
  9. customwas removed in vacuo
  10. customto afford a pale yellow solid
  11. customThe crude material was purified by column chromatography on silica gel (0-85% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-d68bcd55fe294489b5dc72e5d2da7f0e
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

Loading…