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

HRID 592454Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 592454
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]

Komponenten

8

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8471TriethylamineLösungsmittel

Versuchsvorschrift

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]+.

Aufarbeitung

  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.)

Quellen und Nachweise

ORD-Eintrag
ord-f14c318345c34dc4be7d886e096937f6
Quelldatensatz
uspto-grants-2016_01
Patentnummer
US09238644B2

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