Sodium Chloride → {1-[(4-phenyl-1,3-thiazol-2-yl)methyl]cyclobutyl}methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate

HRID 1180769

Reaktionsgleichung

Reaktionsgleichung von HRID 1180769
[C:1]1([C:7]2[N:8]=[C:9]([CH2:12][C:13]3([CH2:17][OH:18])[CH2:16][CH2:15][CH2:14]3)[S:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:19](Cl)(Cl)=[O:20].[NH2:23][C@@H:24]([CH2:38][CH2:39][CH2:40][CH3:41])[CH:25]([OH:37])[C:26]([NH:28][C@@H:29]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH3:30])=[O:27].C(N(CC)C(C)C)(C)C.[Cl-].[Na+]>ClCCl.C1(C)C=CC=CC=1.O1CCCC1.C(OCC)(=O)C>[OH:37][CH:25]([C@@H:24]([NH:23][C:19](=[O:20])[O:18][CH2:17][C:13]1([CH2:12][C:9]2[S:10][CH:11]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[N:8]=2)[CH2:16][CH2:15][CH2:14]1)[CH2:38][CH2:39][CH2:40][CH3:41])[C:26](=[O:27])[NH:28][C@@H:29]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[CH3:30]

Komponenten

10

Edukt 5

HCID 5234Sodium ChlorideHCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 11265560(3S)-3-amino-2-hydroxy-N-[(1R)-1-phenylethyl]heptanamideHCID 11737047{1-[(4-Phenyl-1,3-thiazol-2-yl)methyl]cyclobutyl}methanol

Produkt 1

HCID 11753176{1-[(4-phenyl-1,3-thiazol-2-yl)methyl]cyclobutyl}methyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamateAusbeute 98,2 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 1140TolueneLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of 0.16 g (0.63 mmol) of {1-[(4-phenyl-1,3-thiazol-2-yl)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 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 7 h, 30 mL of ethyl acetate and 20 mL of saturated sodium chloride were 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 using ethyl acetate:hexane (1:1) as the eluent to afford 0.34 g (98%) of {1-[(4-phenyl-1,3-thiazol-2-yl)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 7.90, 7.92 (2s, 1H), 7.46-7.18 (m, 10 H), 5.61 (d, J=9 Hz, 1H), 5.14-5.01 (m, 2H), 4.19-4.06 (m, 4H), 3.88 (m, 1H), 3.23 (s, 2H), 2.21-1.50 (m, 10 H), 1.46 (d, J=7 Hz, 3H), 1.37-1.27 (m, 2H), 0.94 (m, 3H). LC-MS m/z 550 (M+H).

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe residue was dissolved in 3 mL of tetrahydrofuran
  3. stirringAfter stirring for 7 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

Quellen und Nachweise

ORD-Eintrag
ord-e7fbfbd0f2d34a368692cf53ba6b0f18
Quelldatensatz
uspto-grants-2007_10
Patentnummer
US07282512B2

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