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

HRID 592454ノート

反応式

HRID 592454 の反応式
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]

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8471Triethylamine溶媒

実験手順

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]+.

後処理

  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.)

出典と根拠

ORDレコード
ord-f14c318345c34dc4be7d886e096937f6
出典データセット
uspto-grants-2016_01
特許番号
US09238644B2

反応ノート

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