Sodium Chloride → (1-{[(1-methyl-1H-imidazol-2-yl)sulfanyl]methyl}cyclobutyl)methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate

HRID 1180772

Reaktionsgleichung

Reaktionsgleichung von HRID 1180772
[CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[C:3]1[S:7][CH2:8][C:9]1([CH2:13][OH:14])[CH2:12][CH2:11][CH2:10]1.[C:15](Cl)(Cl)=[O:16].[NH2:19][C@@H:20]([CH2:34][CH2:35][CH2:36][CH3:37])[CH:21]([OH:33])[C:22]([NH:24][C@@H:25]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH3:26])=[O:23].C(N(CC)C(C)C)(C)C.[Cl-].[Na+]>ClCCl.C1(C)C=CC=CC=1.O1CCCC1.C(OCC)(=O)C>[OH:33][CH:21]([C@@H:20]([NH:19][C:15](=[O:16])[O:14][CH2:13][C:9]1([CH2:8][S:7][C:3]2[N:2]([CH3:1])[CH:6]=[CH:5][N:4]=2)[CH2:10][CH2:11][CH2:12]1)[CH2:34][CH2:35][CH2:36][CH3:37])[C:22](=[O:23])[NH:24][C@@H:25]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH3:26]

Komponenten

10

Edukt 5

HCID 5234Sodium ChlorideHCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 11265560(3S)-3-amino-2-hydroxy-N-[(1R)-1-phenylethyl]heptanamideHCID 11435800(1-{[(1-methyl-1H-imidazol-2-yl)sulfanyl]methyl}cyclobutyl)methanol

Produkt 1

HCID 11397962(1-{[(1-methyl-1H-imidazol-2-yl)sulfanyl]methyl}cyclobutyl)methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamateAusbeute 70 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 1140TolueneLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of 0.132 g (0.625 mmol) of (1-{[(1-methyl-1H-imidazol-2-yl)sulfanyl]methyl}cyclobutyl) methanol in 2 mL of dichloromethane cooled to 0° C. was added a 1.0 M solution of 0.94 mL (1.41 mmol) of phosgene in toluene and the contents were stirred for 16 h. The reaction mixture was concentrated and the residue was dissolved in 3 mL of tetrahydrofuran, and added to a 0° C. solution of 0.165 g (0.63 mmol) of (3S)-3-amino-2-hydroxy-N-[(1R)-1-phenylethyl]heptanamide and 0.325 mL (1.89 mmol) of N,N-diisopropylethylamine in 2 mL of tetrahydrofuran. After stirring for 6 h, 30 mL of ethyl acetate and 20 mL of saturated sodium chloride was added. The organic phase was isolated, dried using magnesium sulfate, and concentrated under vacuum to afford the crude product which was purified by silica gel chromatography eluting with ethyl acetate to afford 0.220 g (70%) of (1-{[(1-methyl-1H-imidazol-2-yl)sulfanyl]methyl}cyclobutyl)methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate as a colorless oil. 1H NMR (300 MHz, CDCl3)) δ 7.63-7.52 (m, 1H), 7.41 (m, 1H), 7.39-7.15 (m, 5H), 6.91, 6.98 (2s, 1H), 6.03 (br s, 1H), 5.69 (m, 1H), 5.19-5.11 (m, 1H), 4.18-3.95 (m, 4H), 3.61, 3.63 (2s, 2H), 3.28 (m, 2H), 2.21-1.61 (m, 10H), 1.60-1.16 (m, 5H), 0.90 (m, 3H). LC-MS m/z 503 (M+H).

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe residue was dissolved in 3 mL of tetrahydrofuran
  3. stirringAfter stirring for 6 h
  4. customThe organic phase was isolated
  5. customdried
  6. concentrationconcentrated under vacuum
  7. customto afford the crude product which
  8. customwas purified by silica gel chromatography
  9. washeluting with ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-3feacce7c9fb4b0e939f4645d1eb37c2
Quelldatensatz
uspto-grants-2007_10
Patentnummer
US07282512B2

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