Acetyl chloride → HCID 178502293, 화합물

HRID 454436노트

반응식

HRID 454436 반응식
[CH3:1][CH:2]([CH3:59])[C@H:3]([NH:54][C:55](=[O:58])[O:56][CH3:57])[C:4]([N:6]1[CH2:10][CH2:9][CH2:8][C@H:7]1[C:11]1[NH:12][CH:13]=[C:14]([C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:27]=[CH:26][C:25]([C:28]4[N:29]=[C:30]([CH:33]5[CH2:37][C:36]6([CH2:42][CH2:41][NH:40][CH2:39][CH2:38]6)[CH2:35][N:34]5[C:43](=[O:53])[C@@H:44]([NH:48][C:49]([O:51][CH3:52])=[O:50])[CH:45]([CH3:47])[CH3:46])[NH:31][CH:32]=4)=[CH:24][CH:23]=3)=[CH:18][CH:17]=2)[N:15]=1)=[O:5].C(N(CC)CC)C.[C:67](Cl)(=[O:69])C.[C:71](=O)([O-])[O-:72].[K+].[K+]>C(Cl)Cl>[CH3:52][O:51][C:49]([NH:48][C@H:44]([C:43]([N:34]1[CH:33]([C:30]2[NH:31][CH:32]=[C:28]([C:25]3[CH:24]=[CH:23][C:22]([C:19]4[CH:20]=[CH:21][C:16]([C:14]5[N:15]=[C:11]([C@@H:7]6[CH2:8][CH2:9][CH2:10][N:6]6[C:4](=[O:5])[C@H:3]([CH:2]([CH3:59])[CH3:1])[NH:54][C:55]([O:56][CH3:57])=[O:58])[NH:12][CH:13]=5)=[CH:17][CH:18]=4)=[CH:27][CH:26]=3)[N:29]=2)[CH2:37][C:36]2([CH2:38][CH2:39][N:40]([C:71]([O:69][CH3:67])=[O:72])[CH2:41][CH2:42]2)[CH2:35]1)=[O:53])[CH:45]([CH3:46])[CH3:47])=[O:50]

참가 물질

6

반응물 4

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 178502291HCID 178502291, 화합물

생성물 1

HCID 178502293HCID 178502293, 화합물수율 86.6%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of methyl [(1S)-2-methyl-1-({(2S)-2-[4-(4′-{2-[2-((2S)-3-methyl-2-{[(methyloxy)carbonyl]amino}butanoyl)-2,8-diazaspiro[4.5]dec-3-yl]-1H-imidazol-4-yl}-4-biphenylyl)-1H-imidazol-2-yl]-1-pyrrolidinyl}carbonyl)propyl]carbamate (Example 20) (19 mg, 0.02 mmol) in anhydrous CH2Cl2 (0.5 mL) was added triethylamine (0.016 mL, 0.12 mmol) followed by acetyl chloride (0.011 mL, 0.14 mmol) and the reaction stirred at room temperature for 1 h. The reaction is concentrated in vacuo and dissolved in methanol (0.7 mL) to which was added potassium carbonate (30 mg, 0.22 mmol) and the reaction was stirred at room temperature for 2 h. The reaction was concentrated in vacuo and partitioned between CH2Cl2 and water (3 mL each) and the aqueous layer extracted with CH2Cl2 (3 mL) and the organic layers combined and dried (MgSO4) and concentrated in vacuo to afford the title compound as a yellow solid (15 mg, 74% yield). 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.51-7.92 (m, 10H) 7.32 (br. s., 2H) 5.02-5.25 (m, 1H) 4.03-4.31 (m, 2H) 3.75-4.05 (m, 2H) 3.61-3.72 (m, 7H) 3.34-3.60 (m, 4H) 1.82-2.50 (m, 7H) 1.70 (br. s., 2H) 1.44-1.63 (m, 4H) 1.27 (br. s., 4H) 0.77-1.10 (m, 14H). HRMS for C46H60N9O8 (M+H)+ calc: 866.4565, found: 850.4564. Purity (LC-MS): 96%.

후처리

  1. concentrationThe reaction is concentrated in vacuo
  2. dissolutiondissolved in methanol (0.7 mL) to which
  3. stirringthe reaction was stirred at room temperature for 2 h
  4. concentrationThe reaction was concentrated in vacuo
  5. custompartitioned between CH2Cl2 and water (3 mL each)
  6. extractionthe aqueous layer extracted with CH2Cl2 (3 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-90b29358973e48de8afa2a28cad3b8e6
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08492554B2

반응 노트

불러오는 중…