Potassium Carbonate → Ethyl 4-(4-chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate

HRID 528790

반응식

HRID 528790 반응식
F[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][C:3]=1[C:13]([N:15]1[CH2:24][CH2:23][C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH2:16]1)=[O:14].[CH2:25]([N:29]([CH2:39][CH2:40][CH2:41][CH3:42])[C:30]([C:32]1[C:36]([Cl:37])=[C:35]([CH3:38])[NH:34][N:33]=1)=[O:31])[CH2:26][CH2:27][CH3:28].C([O-])([O-])=O.[K+].[K+]>CN1C(=O)CCC1>[Cl:37][C:36]1[C:32]([C:30](=[O:31])[N:29]([CH2:39][CH2:40][CH2:41][CH3:42])[CH2:25][CH2:26][CH2:27][CH3:28])=[N:33][N:34]([C:2]2[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][C:3]=2[C:13]([N:15]2[CH2:24][CH2:23][C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[CH2:16]2)=[O:14])[C:35]=1[CH3:38]

참가 물질

5

반응물 3

HCID 11430Potassium CarbonateHCID 71061015Ethyl 4-fluoro-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoateHCID 71062189N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide

생성물 1

HCID 71062392Ethyl 4-(4-chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate수율 81.5%

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매

반응 조건

온도
125 °C

실험 절차

To a solution of ethyl 4-fluoro-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate (645 mg, 1.97 mmol) and N,N-dibutyl-4-chloro-5-methyl-1H-pyrazole-3-carboxamide (1.07 g, 3.94 mmol) in NMP (9.9 mL) was added K2CO3 (1.09 g, 7.88 mmol). The resulting reaction mixture was stirred at 125° C. for 3 h, cooled to room temperature and quenched with 10% aq. LiCl solution. The solution was extracted with EtOAc (3×) and the combined organic extracts were washed with 10% LiCl (3×), dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography (25% EtOAc/CHCl3) to afford the title compound (930 mg, 81%). 1H NMR (DMSO-d6, 2:1 mixture of amide rotamers) δ 8.32 (s, 0.5H), 8.23-8.13 (m, 1H), 8.11-8.00 (m, 1H), 7.76-7.87 (m, 0.5H), 7.28-7.08 (m, 3.5H), 7.03-6.94 (m, 0.5H), 4.87-4.51 (m, 2H), 4.43-4.27 (m, 2.5H), 3.86-3.75 (m, 0.5H), 3.63-3.32 (m, 3H), 3.23-3.07 (m, 1H), 3.05-2.94 (m, 1H), 2.85-2.62 (m, 2H), 2.27 (s, 2H), 2.22 (s, 1H), 1.48-1.09 (m, 9H), 1.04-0.92 (m, 2H), 0.90-0.82 (m, 3H), 0.70-0.63 (m, 3H); MS(ESI+) m/z 579.4 (M+H)+.

후처리

  1. customThe resulting reaction mixture
  2. temperaturecooled to room temperature
  3. customquenched with 10% aq. LiCl solution
  4. extractionThe solution was extracted with EtOAc (3×)
  5. washthe combined organic extracts were washed with 10% LiCl (3×)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash chromatography (25% EtOAc/CHCl3)

출처 및 근거

ORD 기록
ord-9ae917b1581c42d592879b9277d79fa3
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346795B2

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