Sodium Iodide → tert-butyl 2-((8-(3-(3-cyclopropyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

HRID 1751086노트

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HRID 1751086 반응식
[O:1]=[C:2]1[C:6]2([CH2:11][CH2:10][NH:9][CH2:8][CH2:7]2)[N:5]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:4][N:3]1[CH2:18][C:19]1[CH:31]=[CH:30][CH:29]=[CH:28][C:20]=1[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22].Cl[CH2:33][CH2:34][CH2:35][N:36]1[C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=2[N:38]([CH:45]2[CH2:47][CH2:46]2)[C:37]1=[O:48].[I-].[Na+].C(=O)([O-])[O-].[K+].[K+]>CC(=O)CC>[CH:45]1([N:38]2[C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=3[N:36]([CH2:35][CH2:34][CH2:33][N:9]3[CH2:8][CH2:7][C:6]4([N:5]([C:12]5[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=5)[CH2:4][N:3]([CH2:18][C:19]5[CH:31]=[CH:30][CH:29]=[CH:28][C:20]=5[C:21]([O:23][C:24]([CH3:27])([CH3:25])[CH3:26])=[O:22])[C:2]4=[O:1])[CH2:11][CH2:10]3)[C:37]2=[O:48])[CH2:47][CH2:46]1

참가 물질

6

반응물 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 580467891-(3-chloropropyl)-3-cyclopropyl-1H-benzo[d]imidazol-2(3H)-oneHCID 66652177Tert-butyl 2-((4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

생성물 1

HCID 58046683tert-butyl 2-((8-(3-(3-cyclopropyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate수율 76.2%

시약·촉매·용매 1

HCID 6569Methyl Ethyl Ketone용매

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온도
81 °C

실험 절차

A mixture of tert-butyl 2-((4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate (200 mg, 0.475 mmol, 1 equiv), 1-(3-chloropropyl)-3-cyclopropyl-1H-benzo[d]imidazol-2(3H)-one (118.75 mg, 0.475 mmol, 1 equiv), sodium iodide (28.5 mg, 0.19 mmol, 0.4 equiv) and potassium carbonate (131.3 mg, 0.95 mmol, 2 equiv) in 2-butanone was stirred at 81° C. for 16 h. After cooling the reaction mixture, the crude mixture was partitioned between ethyl acetate and water. The organic layer was dried over MgSO4, filtered, concentrated, and the crude residue was purified using the Biotage flash chromatography system (SNAP 10 g cartridge, Rf=0.5, gradient—1%-10% methanol in dichloromethane) to afford the title compound (230 mg, 76%); 1H NMR (400 MHz, DMSO-d6): δ 0.85-0.89 (m, 2H); 0.95-1.04 (m, 2H); 1.57 (s, 9H); 1.67 (d, 2H, J=12.4 Hz); 1.81 (t, 2H, J=6.4 and 6.8 Hz); 2.32-2.35 (t, 2H, J=6.8 Hz); 2.54-2.72 (m, 6H); 2.86-2.89 (m, 1H); 3.84-3.88 (t, 2H, J=6.8 and 6.4 Hz); 4.62 (s, 2H); 4.84 (s, 2H); 6.76-6.79 (t, 1H, J=7.2 Hz); 6.84-6.86 (d, 2H, J=8.4 Hz); 7.03-7.06 (t, 2H, J=5.6 and 6.8 Hz); 7.19-7.27 (m, 5H); 7.39-7.43 (t, 1H, J=7.6 and 7.2 Hz); 7.56-7.59 (t, 1H, J=8 and 6.4 Hz); 7.82-7.84 (d, 1H, J=7.6 Hz); MS for C38H45N5O4 m/z 636.12 (M+H)+.

후처리

  1. temperatureAfter cooling the reaction mixture
  2. customthe crude mixture was partitioned between ethyl acetate and water
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customthe crude residue was purified

출처 및 근거

ORD 기록
ord-5820ee23636740af8504bf87dfed9983
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09156840B2

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