Diisopropylethylamine → HCID 86693892, Verbindung

HRID 404841Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 404841
[CH2:1]([C:8]1[S:12][C:11]([C:13]2[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=2[F:20])=[N:10][C:9]=1[C@H:21]([NH:26][CH2:27][C@H:28]1[C@@H:32]([F:33])[CH2:31][N:30]([C:34]([O:36][CH2:37][C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)=[O:35])[CH2:29]1)[C:22]([CH3:25])([CH3:24])[CH3:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[C:53]([O:56][C@@H:57]([CH3:61])[C:58](Cl)=[O:59])(=[O:55])[CH3:54]>ClCCl>[C:53]([O:56][C@@H:57]([CH3:61])[C:58]([N:26]([CH2:27][C@H:28]1[C@@H:32]([F:33])[CH2:31][N:30]([C:34]([O:36][CH2:37][C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)=[O:35])[CH2:29]1)[C@@H:21]([C:9]1[N:10]=[C:11]([C:13]2[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=2[F:20])[S:12][C:8]=1[CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)[C:22]([CH3:25])([CH3:24])[CH3:23])=[O:59])(=[O:55])[CH3:54]

Komponenten

5

Edukt 3

HCID 81531DiisopropylethylamineHCID 11094804(1S)-2-Chloro-1-methyl-2-oxoethyl acetateHCID 86693891(3R,4R)-benzyl 3-(((R)-1-(5-benzyl-2-(2,5-difluorophenyl)thiazol-4-yl)-2,2-dimethylpropylamino)methyl)-4-fluoropyrrolidine-1-carboxylate

Produkt 1

HCID 86693892HCID 86693892, VerbindungAusbeute 75 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

to a solution of (3R,4R)-benzyl 3-(((R)-1-(5-benzyl-2-(2,5-difluorophenyl)thiazol-4-yl)-2,2-dimethylpropylamino)methyl)-4-fluoropyrrolidine-1-carboxylate (130 mg, 0.214 mmol) in dichloromethane (2.1 mL, 0.1 M solution) at room temperature was added N,N-diisopropylethylamine (112 μL, 0.64 mmol). (S)-1-Chloro-1-oxopropan-2-yl acetate (54.2 μL, 0.428 mmol) was then added dropwise over 2 min. The resulting solution was stirred at room temperature for 2 h. The reaction mixture was quenched with saturated NaHCO3 solution and extracted with EtOAc. The organic layer was washed with water and brine, dried over anhydrous sodium sulfate and filtered. After the volatile organic materials were removed in vacuo, the crude product was purified on flash column chromatography to yield (3R,4R)-benzyl 3-(((S)-2-acetoxy-N-((R)-1-(5-benzyl-2-(2,5-difluorophenyl)thiazol-4-yl)-2,2-dimethylpropyl)propanamido)methyl)-4-fluoropyrrolidine-1-carboxylate (115 mg, 75%). NMR (CDCl3, 400 MHz): δ 7.85 (1H, m), 7.37-7.24 (7H, m), 7.21 (1H, m), 7.09 (2H, m), 7.05 (1H, m), 6.96 (1H, m), 6.1 (1H, m), 5.4 (2H, m), 5.28 (1H, m), 4.82 (2H, m), 4.19-3.97 (3H, m), 3.70-3.49 (2H, m), 3.13 (1H, m), 2.76 (1H, m), 2.52 (1H, m), 2.18 (3H, s), 1.61 (3H, m), 0.99 (9H, s). LC/MS (uplc): MH+ 722.3, 1.40 min.

Aufarbeitung

  1. customThe reaction mixture was quenched with saturated NaHCO3 solution
  2. extractionextracted with EtOAc
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customAfter the volatile organic materials were removed in vacuo
  7. customthe crude product was purified on flash column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-1c88fa39a38243f5806b3544b3e99e6f
Quelldatensatz
uspto-grants-2014_06
Patentnummer
US08748626B2

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