Potassium Carbonate → HCID 178485813, Verbindung

HRID 454441Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 454441
[CH3:1][CH:2]([CH3:57])[C@H:3]([NH:52][C:53](=[O:56])[O:54][CH3:55])[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[CH2:40][C:36]6([CH2:39][NH:38][CH2:37]6)[CH2:35][N:34]5[C:41](=[O:51])[C@@H:42]([NH:46][C:47]([O:49][CH3:50])=[O:48])[CH:43]([CH3:45])[CH3:44])[NH:31][CH:32]=4)=[CH:24][CH:23]=3)=[CH:18][CH:17]=2)[N:15]=1)=[O:5].[CH3:58][N:59]=[C:60]=[O:61].C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl>[CH3:1][CH:2]([CH3:57])[C@H:3]([NH:52][C:53](=[O:56])[O:54][CH3:55])[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:23]=[CH:24][C:25]([C:28]4[N:29]=[C:30]([CH:33]5[CH2:40][C:36]6([CH2:37][N:38]([C:60]([NH:59][CH3:58])=[O:61])[CH2:39]6)[CH2:35][N:34]5[C:41](=[O:51])[C@@H:42]([NH:46][C:47]([O:49][CH3:50])=[O:48])[CH:43]([CH3:44])[CH3:45])[NH:31][CH:32]=4)=[CH:26][CH:27]=3)=[CH:18][CH:17]=2)[N:15]=1)=[O:5]

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 12228Methyl IsocyanateHCID 178502299methyl N-[(1S)-1-[(2S)-2-[5-[4-[4-[2-[7-[(2S)-2-(methoxycarbonylamino)-3-methyl-butanoyl]-2,7-diazaspiro[3.4]octan-6-yl]-1H-imidazol-5-yl]phenyl]phenyl]-1H-imidazol-2-yl]pyrrolidine-1-carbonyl]-2-methyl-propyl]carbamate

Produkt 1

HCID 178485813HCID 178485813, VerbindungAusbeute 70 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of methyl [(1S)-2-methyl-1-({(2S)-2-[4-(4′-{2-[6-((2S)-3-methyl-2-{[(methyloxy)carbonyl]amino}butanoyl)-2,6-diazaspiro[3.4]oct-7-yl]-1H-imidazol-4-yl}-4-biphenylyl)-1H-imidazol-2-yl]-1-pyrrolidinyl}carbonyl)propyl]carbamate (Example 24) (45 mg, 0.06 mmol) in anhydrous CH2Cl2 (0.6 mL) was added methyl isocyanate (0.01 mL, 0.17 mmol) and the reaction stirred at room temperature for 2 h. The solvent was removed in vacuo and the residue dissolved in methanol (1 mL) and potassium carbonate (40 mg, 0.29 mmol) was added and the reaction stirred at room temperature for 18 h. The reaction was partitioned between CH2Cl2 (10 mL) and water (5 mL), the aqueous layer was extracted with CH2Cl2 (5 mL), the organic layers were combined and dried (MgSO4) and concentrated in vacuo to afford the title compound as a yellow solid (34 mg, 70% yield). 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.64 (br. s., 10H) 7.33 (br. s., 2H) 5.06-5.22 (m, 1H) 4.03-4.46 (m, 3H) 3.73-4.04 (m, 8H) 3.54-3.73 (m, 6H) 3.46 (q, J=7.0 Hz, 2H) 2.52-2.76 (m, 5H) 2.10-2.53 (m, 4H) 2.02 (br. s., 3H) 0.70-1.09 (m, 12H). HRMS for C44H57N10O7 (M+H)+ calc: 837.4412, found: 838.4416. Purity (LC-MS): 91%.

Aufarbeitung

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue dissolved in methanol (1 mL)
  3. stirringthe reaction stirred at room temperature for 18 h
  4. customThe reaction was partitioned between CH2Cl2 (10 mL) and water (5 mL)
  5. extractionthe aqueous layer was extracted with CH2Cl2 (5 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-530758012d4a4a4bae348b7571e06498
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08492554B2

Notizen zur Reaktion

Wird geladen…