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

HRID 592454노트

반응식

HRID 592454 반응식
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]

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8471Triethylamine용매

실험 절차

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]+.

후처리

  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.)

출처 및 근거

ORD 기록
ord-f14c318345c34dc4be7d886e096937f6
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09238644B2

반응 노트

불러오는 중…