Hydrochloric Acid → tert-Butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzoyl)piperazine-1-carboxylate

HRID 1778983Notes

Reaction equation

HRID 1778983 reaction equation
C1C=CC2N(O)N=[N:7]C=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.CCN(C(C)C)C(C)C.C[O:34][C:35](=O)[CH2:36][C:37]1[CH:76]=[CH:75][CH:74]=[CH:73][C:38]=1[CH2:39][CH2:40][C:41]1[C:46]([C:47]([F:50])([F:49])[F:48])=[CH:45][N:44]=[C:43]([NH:51][C:52]2[CH:72]=[CH:71][C:55]([C:56]([N:58]3[CH2:63][CH2:62][N:61]([C:64]([O:66][C:67]([CH3:70])([CH3:69])[CH3:68])=[O:65])[CH2:60][CH2:59]3)=[O:57])=[CH:54][CH:53]=2)[N:42]=1.C(=O)([O-])[O-].[NH4+].[NH4+]>C1COCC1.CN(C=O)C>[NH2:7][C:35](=[O:34])[CH2:36][C:37]1[CH:76]=[CH:75][CH:74]=[CH:73][C:38]=1[CH2:39][CH2:40][C:41]1[C:46]([C:47]([F:50])([F:48])[F:49])=[CH:45][N:44]=[C:43]([NH:51][C:52]2[CH:72]=[CH:71][C:55]([C:56]([N:58]3[CH2:59][CH2:60][N:61]([C:64]([O:66][C:67]([CH3:68])([CH3:69])[CH3:70])=[O:65])[CH2:62][CH2:63]3)=[O:57])=[CH:54][CH:53]=2)[N:42]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 517111Ammonium CarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86712648tert-Butyl 4-(4-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzoyl)piperazine-1-carboxylate

Product 1

HCID 86712649tert-Butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzoyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

HOBt (0.068 g, 0.50 mmol), EDCl.HCl (0.096 g, 0.50 mmol) and DIPEA (0.34 mL, 1.9 mmol) were added to a stirred solution of tert-butyl 4-(4-((4-(2-(2-methoxy-2-oxoethyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)benzoyl)piperazine-1-carboxylate (A25) (0.28 g, 0.39 mmol) in dry THF (6 mL) and dry DMF (1 mL) under an atmosphere of nitrogen. After 10 minutes ammonium carbonate (0.19 g, 1.9 mmol) was added in one portion and the resulting solution was stirred at room temperature for 17 hours. The volatiles were removed in vacuo and the residue was partitioned between EtOAc (65 mL) and saturated aqueous NaHCO3 (65 mL). The aqueous layer was extracted with EtOAc (2×50 mL) then the combined organic layers were washed with brine (50 mL) and dried over MgSO4. The volatiles were removed in vacuo and the residue was purified by silica gel column chromatography (Biotage Isolera, 25 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C. then 0-20% MeOH in EtOAc) to give the title compound A26 as a white solid (0.18 g, 77%); 1H NMR (400 MHz, CDCl3) δ 8.58 (s, 1H), 7.91 (s, 1H), 7.72 (d, J=8.4 Hz, 2H), 7.44 (d, J=8.3 Hz, 2H), 7.31-7.21 (m, obscured), 5.43 (br. s, 2H), 3.74 (s, 2H), 3.71-3.35 (m, 8H), 3.18-3.03 (m, 4H), 1.47 (s, 9H). LCMS-A: rt 6.120 min; m/z 613.3 [M+H]+.

Workup

  1. customThe volatiles were removed in vacuo
  2. customthe residue was partitioned between EtOAc (65 mL) and saturated aqueous NaHCO3 (65 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
  4. washthe combined organic layers were washed with brine (50 mL)
  5. dry with materialdried over MgSO4
  6. customThe volatiles were removed in vacuo
  7. customthe residue was purified by silica gel column chromatography (Biotage Isolera, 25 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.

Sources & evidence

ORD record
ord-979bc97117f74c28b458b2ab142afbe4
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

Loading…