Diisopropylethylamine → methyl (1S)-1-[({(1R,3S,4S)-4-{[(2S)-2-(3-benzyl-2-oxo-1-imidazolidinyl)-3,3-dimethylbutanoyl]amino}-3-hydroxy-5-phenyl-1-[4-(2-pyridinyl)benzyl]pentyl}amino)carbonyl]-2,2-dimethylpropylcarbamate

HRID 1174234Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1174234
[NH2:1][C@@H:2]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C@@H:3]([OH:32])[CH2:4][C@H:5]([NH:19][C:20]([C@@H:22]([NH:27][C:28](=[O:31])[O:29][CH3:30])[C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[CH:9][CH:8]=1.[CH2:40]([N:47]1[CH2:51][CH2:50][N:49]([C@@H:52]([C:56]([CH3:59])([CH3:58])[CH3:57])[C:53](O)=[O:54])[C:48]1=[O:60])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.CCOP(ON1N=NC2C=CC=CC=2C1=O)(OCC)=O.C(N(CC)C(C)C)(C)C>C1COCC1>[CH2:40]([N:47]1[CH2:51][CH2:50][N:49]([C@@H:52]([C:56]([CH3:58])([CH3:57])[CH3:59])[C:53]([NH:1][C@@H:2]([CH2:33][C:34]2[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)[C@@H:3]([OH:32])[CH2:4][C@H:5]([NH:19][C:20]([C@@H:22]([NH:27][C:28](=[O:31])[O:29][CH3:30])[C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:6][C:7]2[CH:12]=[CH:11][C:10]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=3)=[CH:9][CH:8]=2)=[O:54])[C:48]1=[O:60])[C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1

Komponenten

6

Edukt 4

HCID 81531DiisopropylethylamineHCID 42939953-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-oneHCID 42625467methyl (1S)-1-[({(1R,3S,4S)-4-amino-3-hydroxy-5-phenyl-1-[4-(2-pyridinyl)benzyl]pentyl}amino)carbonyl]-2,2-dimethylpropylcarbamateHCID 42626247(2S)-2-(3-benzyl-2-oxo-1-imidazolidinyl)-3,3-dimethylbutanoic acid

Produkt 1

HCID 42625714methyl (1S)-1-[({(1R,3S,4S)-4-{[(2S)-2-(3-benzyl-2-oxo-1-imidazolidinyl)-3,3-dimethylbutanoyl]amino}-3-hydroxy-5-phenyl-1-[4-(2-pyridinyl)benzyl]pentyl}amino)carbonyl]-2,2-dimethylpropylcarbamateAusbeute 74,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

A solution containing the product from Example 1H (0.040 g, 0.075 mmol) in THF (0.6 mL) was treated with the product from Example 70A (0.027 g, 0.092 mmol), DEPBT (0.034 g, 0.114 mmol), and N,N-diisopropylethylamine (0.066 mL, 0.379 mmol), stirred at 25° C. for 16 hours, and partitioned between ethyl acetate and 10% Na2CO3 solution. The organic phase was washed with additional 10% Na2CO3 solution and brine, dried over MgSO4, filtered and concentrated. The residue was chromatographed on silica gel eluting with 0-100% ethyl acetate/dichloromethane, followed by elution with 0-5% methanol in ethyl acetate to give the title compound (0.045 g, 73% yield). 1H NMR (300 MHz, DMSO-d6), δ ppm 0.80 (s, 9 H), 0.87 (s, 9 H), 1.38 (t, J=11.58 Hz, 1 H), 1.54 (m, 1 H), 2.41 (m, 1 H), 2.64 (m, 3 H), 2.87 (m, 3 H), 3.19 (m, 1 H), 3.53 (m, 4 H), 3.84 (d, J=9.56 Hz, 1 H), 3.95 (m, 1 H), 4.04 (s, 1 H), 4.18 (m, 1 H), 4.29 (m, 2 H), 4.45 (d, J=7.35 Hz, 1 H), 6.88 (d, J=9.56 Hz, 1 H), 7.05 (m, 5 H), 7.30 (m, 8 H), 7.53 (d, J=9.56 Hz, 1 H), 7.90 (m, 5 H), 8.65 (d, J=4.41 Hz, 1 H).

Aufarbeitung

  1. custompartitioned between ethyl acetate and 10% Na2CO3 solution
  2. washThe organic phase was washed with additional 10% Na2CO3 solution and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was chromatographed on silica gel eluting with 0-100% ethyl acetate/dichloromethane
  7. washfollowed by elution with 0-5% methanol in ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-a3d80b6d49804de0b3acf2db5b66561a
Quelldatensatz
uspto-grants-2010_11
Patentnummer
US07834043B2

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