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

HRID 592454Notes

Reaction equation

HRID 592454 reaction equation
C(=O)([O-])[O-].[NH4+].[NH4+].[C:7]([O:11][C:12]([N:14]1[CH2:19][CH2:18][CH:17]([C:20]2[CH:25]=[CH:24][C:23]([NH:26][C:27]3[N:32]=[C:31]([CH2:33][CH2:34][C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=4[C:41]4([C:45]([OH:47])=O)[CH2:44][CH2:43][CH2:42]4)[C:30]([C:48]([F:51])([F:50])[F:49])=[CH:29][N:28]=3)=[CH:22][CH:21]=2)[CH2:16][CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8].C1C=CC2N(O)N=[N:58]C=2C=1.CCN=C=NCCCN(C)C.Cl.Cl>CCN(CC)CC.CN(C=O)C>[C:45]([C:41]1([C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=2[CH2:34][CH2:33][C:31]2[C:30]([C:48]([F:49])([F:51])[F:50])=[CH:29][N:28]=[C:27]([NH:26][C:23]3[CH:24]=[CH:25][C:20]([CH:17]4[CH2:18][CH2:19][N:14]([C:12]([O:11][C:7]([CH3:8])([CH3:10])[CH3:9])=[O:13])[CH2:15][CH2:16]4)=[CH:21][CH:22]=3)[N:32]=2)[CH2:42][CH2:43][CH2:44]1)(=[O:47])[NH2:58]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 517111Ammonium CarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 867123301-(2-(2-(2-((4-(1-(tert-Butoxycarbonyl)piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)cyclobutanecarboxylic acid

Product 1

HCID 86712331tert-Butyl 4-(4-((4-(2-(1-carbamoylcyclobutyl)phenethyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Ammonium carbonate (92 mg 0.96 mmol) was added to a suspension of 1-(2-(2-(2-((4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethyl)phenyl)cyclobutanecarboxylic acid A56 (30 mg, 0.048 mmol), HOBt (32 mg, 0.24 mmol) and EDCl.HCl (46 mg, 0.24 mmol) in Et3N (0.2 mL) and DMF (10 mL) and the resulting mixture was stirred at 40° C. overnight. The volatiles were removed in vacuo and the resulting residue was dissolved in DCM (50 mL), washed with water (50 mL), separated and adsorbed onto silica gel. Purification by column chromatography (Biotage Isolera, 12 g SiO2 cartridge, 0-100% EtOAc in peteroleum benzine 40-60° C.) gave the title compound A57 as a yellow solid (6 mg, 20%). LCMS-A: rt 8.604 min; m/z 624.3 [M+H]+.

Workup

  1. customThe volatiles were removed in vacuo
  2. dissolutionthe resulting residue was dissolved in DCM (50 mL)
  3. washwashed with water (50 mL)
  4. customseparated
  5. customPurification by column chromatography (Biotage Isolera, 12 g SiO2 cartridge, 0-100% EtOAc in peteroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-f14c318345c34dc4be7d886e096937f6
Source dataset
uspto-grants-2016_01
Patent number
US09238644B2

Reaction notes

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