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

HRID 1751088노트

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HRID 1751088 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3([CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)[C:11](=[O:18])[N:10]([CH2:19][C:20]3[CH:21]=[C:22]([CH:30]=[CH:31][CH:32]=3)[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:9]2)=[CH:4][CH:3]=1.Cl[CH2:34][CH2:35][CH2:36][N:37]1[C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=2[N:39]([CH:46]2[CH2:48][CH2:47]2)[C:38]1=[O:49].[I-].[Na+].C(=O)([O-])[O-].[K+].[K+]>CC(=O)CC>[CH:46]1([N:39]2[C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=3[N:37]([CH2:36][CH2:35][CH2:34][N:15]3[CH2:14][CH2:13][C:12]4([N:8]([C:5]5[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=5)[CH2:9][N:10]([CH2:19][C:20]5[CH:21]=[C:22]([CH:30]=[CH:31][CH:32]=5)[C:23]([O:25][C:26]([CH3:27])([CH3:28])[CH3:29])=[O:24])[C:11]4=[O:18])[CH2:17][CH2:16]3)[C:38]2=[O:49])[CH2:48][CH2:47]1

참가 물질

6

반응물 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 580467891-(3-chloropropyl)-3-cyclopropyl-1H-benzo[d]imidazol-2(3H)-oneHCID 66652535Tert-butyl 3-((1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate

생성물 1

HCID 58046607tert-butyl 3-((8-(3-(3-cyclopropyl-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)-1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate수율 68.3%

시약·촉매·용매 1

HCID 6569Methyl Ethyl Ketone용매

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온도
81 °C

실험 절차

A mixture of tert-butyl 3-((1-(4-fluorophenyl)-4-oxo-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate (163.5 mg, 0.372 mmol, 1 equiv), 1-(3-chloropropyl)-3-cyclopropyl-1H-benzo[d]imidazol-2(3H)-one (93 mg, 0.372 mmol, 1 equiv), sodium iodide (22.3 mg, 0.15 mmol, 0.4 equiv) and potassium carbonate (102.8 mg, 0.74 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 (166 mg, 68%); MS for C38H44FN5O4 m/z 654.24 (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-e745662fb0d246cda82a641c9371ac53
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09156840B2

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