Hydrochloric Acid → tert-Butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)-5-fluorophenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

HRID 1779016Notes

Reaction equation

HRID 1779016 reaction equation
C1C=CC2N(O)N=[N:7]C=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[C:24]([O:28][C:29]([N:31]1[CH2:36][CH2:35][CH:34]([C:37]2[CH:42]=[CH:41][C:40]([NH:43][C:44]3[N:49]=[C:48]([CH2:50][CH2:51][C:52]4[CH:57]=[C:56]([F:58])[CH:55]=[CH:54][C:53]=4[CH2:59][C:60]([O-])=[O:61])[C:47]([C:63]([F:66])([F:65])[F:64])=[CH:46][N:45]=3)=[CH:39][CH:38]=2)[CH2:33][CH2:32]1)=[O:30])([CH3:27])([CH3:26])[CH3:25].[Li+].CCN(CC)CC.C([O-])(O)=O.[Na+]>CN(C=O)C.C(Cl)Cl>[NH2:7][C:60](=[O:61])[CH2:59][C:53]1[CH:54]=[CH:55][C:56]([F:58])=[CH:57][C:52]=1[CH2:51][CH2:50][C:48]1[C:47]([C:63]([F:65])([F:64])[F:66])=[CH:46][N:45]=[C:44]([NH:43][C:40]2[CH:39]=[CH:38][C:37]([CH:34]3[CH2:35][CH2:36][N:31]([C:29]([O:28][C:24]([CH3:26])([CH3:27])[CH3:25])=[O:30])[CH2:32][CH2:33]3)=[CH:42][CH:41]=2)[N:49]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86712667Lithium 2-(2-(2-(2-((4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)-4-fluorophenyl)acetate

Product 1

HCID 86712669tert-Butyl 4-(4-((4-(2-(2-amino-2-oxoethyl)-5-fluorophenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

HOBt (0.024 g, 0.175 mmol) and EDCl.HCl (0.034 g, 0.175 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)-4-fluorophenyl)acetate (A53) (0.089 g, 0.146 mmol) and Et3N (0.082 mL, 0.585 mmol) in DMF (5 mL) and the resulting mixture stirred at 40° C. overnight. Saturated aqueous NaHCO3 (25 mL) and DCM (25 mL) were added then the layers separated and the aqueous phase extracted with CHCl3 (3×25 mL). The organics were combined then the volatiles were evaporated in vacuo. The residue was adsorbed onto silica gel and purified using column chromatography (Biotage Isolera, 12 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) to yield a clear oil. The oil was triturated with water and the resulting precipitate collected by filtration to give the title compound A54 as a white solid (0.065 g, 74%); 1H NMR (400 MHz, CDCl3) δ 8.47 (d, J=1.0 Hz, 1H), 7.46 (d, J=8.2 Hz, 3H), 7.18-7.09 (m, 3H), 6.95-6.84 (m, 2H), 5.24 (d, J=21.9 Hz, 2H), 4.18 (s, 2H), 3.60 (s, 2H), 3.02 (s, 4H), 2.74 (t, J=10.2 Hz, 2H), 2.58 (m, 1H), 1.76 (d, J=11.7 Hz, 2H), 1.64-1.51 (m, 2H), 1.42 (s, 9H). LCMS-A: rt 6.477 min; m/z 602 [M+H]+.

Workup

  1. customthe layers separated
  2. extractionthe aqueous phase extracted with CHCl3 (3×25 mL)
  3. customthe volatiles were evaporated in vacuo
  4. custompurified
  5. customcolumn chromatography (Biotage Isolera, 12 g SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.)
  6. customto yield a clear oil
  7. customThe oil was triturated with water
  8. filtrationthe resulting precipitate collected by filtration

Sources & evidence

ORD record
ord-999c4dd0af2f4e63a9326d624fdb5404
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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