Acetyl chloride → HCID 178502292, Verbindung

HRID 535136Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 535136
[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])[CH3:68].C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl>[C:67]([N:40]1[CH2:39][CH2:38][C:36]2([CH2:35][N:34]([C:43](=[O:53])[C@@H:44]([NH:48][C:49]([O:51][CH3:52])=[O:50])[CH:45]([CH3:46])[CH3:47])[CH:33]([C:30]3[NH:31][CH:32]=[C:28]([C:25]4[CH:24]=[CH:23][C:22]([C:19]5[CH:20]=[CH:21][C:16]([C:14]6[N:15]=[C:11]([C@@H:7]7[CH2:8][CH2:9][CH2:10][N:6]7[C:4]([C@@H:3]([NH:54][C:55](=[O:58])[O:56][CH3:57])[CH:2]([CH3:59])[CH3:1])=[O:5])[NH:12][CH:13]=6)=[CH:17][CH:18]=5)=[CH:27][CH:26]=4)[N:29]=3)[CH2:37]2)[CH2:42][CH2:41]1)(=[O:69])[CH3:68]

Komponenten

6

Edukt 4

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

Produkt 1

HCID 178502292HCID 178502292, VerbindungAusbeute 105,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

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 (0.01 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 (18 mg, 90% yield). 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.54-7.88 (m, 10H) 7.32 (br. s., 2H) 5.05-5.23 (m, 2H) 4.03-4.34 (m, 2H) 3.71-4.03 (m, 3H) 3.56-3.71 (m, 8H) 3.34-3.56 (m, 2H) 2.14-2.46 (m, 4H) 1.89-2.14 (m, 6H) 1.46-1.83 (m, 4H) 1.19-1.32 (m, 2H) 0.78-1.07 (m, 14H). HRMS for C46H60N9O7 (M+H)+ calc: 850.4616. found: 850.4617. Purity (LC-MS): 94%.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-def3acc435bc4d3db6168e58f1977c6d
Quelldatensatz
uspto-grants-2014_10
Patentnummer
US08853416B2

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