Hydrochloric Acid → (2R,4S)-4-[(3-Cyano-5-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butoxycarbonylmethyl ester

HRID 661461

Reaktionsgleichung

Reaktionsgleichung von HRID 661461
[C:1]([O:5][C:6]([CH2:8][O:9][C:10]([N:12]1[C:21]2[C:16](=[CH:17][C:18]([C:22]([F:25])([F:24])[F:23])=[CH:19][CH:20]=2)[C@@H:15]([NH:26][C:27]2[N:32]=[CH:31][C:30]([N:33]3[CH2:38][CH2:37][O:36][CH2:35][CH2:34]3)=[CH:29][N:28]=2)[CH2:14][C@H:13]1[CH2:39][CH3:40])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[K+].Br[CH2:48][C:49]1[CH:50]=[C:51]([CH:54]=[C:55]([C:57]([F:60])([F:59])[F:58])[CH:56]=1)[C:52]#[N:53].Cl>COC(C)(C)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C>[C:1]([O:5][C:6]([CH2:8][O:9][C:10]([N:12]1[C:21]2[C:16](=[CH:17][C:18]([C:22]([F:23])([F:24])[F:25])=[CH:19][CH:20]=2)[C@@H:15]([N:26]([CH2:48][C:49]2[CH:56]=[C:55]([C:57]([F:58])([F:59])[F:60])[CH:54]=[C:51]([C:52]#[N:53])[CH:50]=2)[C:27]2[N:32]=[CH:31][C:30]([N:33]3[CH2:34][CH2:35][O:36][CH2:37][CH2:38]3)=[CH:29][N:28]=2)[CH2:14][C@H:13]1[CH2:39][CH3:40])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Komponenten

8

Edukt 4

HCID 313Hydrochloric AcidHCID 116013693-(Bromomethyl)-5-(trifluoromethyl)benzonitrileHCID 23665647Potassium tert-butoxideHCID 67140956(2R,4S)-2-Ethyl-4-(5-morpholin-4-yl-pyrimidin-2-ylamino)-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butoxycarbonylmethyl ester

Produkt 1

HCID 86636546(2R,4S)-4-[(3-Cyano-5-trifluoromethyl-benzyl)-(5-morpholin-4-yl-pyrimidin-2-yl)-amino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid tert-butoxycarbonylmethyl ester

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 67553Tetrabutylammonium IodideKatalysatorHCID 8857Ethyl AcetateLösungsmittelHCID 15413tert-Butyl methyl etherLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

The compound obtained in Example 21 (2) above (177 mg) was dissolved in tert-butyl methyl ether (3 ml) under nitrogen atmosphere and the solution was cooled to 0° C. Thereto were added tetrabutylammonium iodide (46 mg), potassium tert-butoxide (105 mg) and 3-Bromomethyl-5-trifluoromethyl-benzonitrile (124 mg), and the mixture was stirred for 2 hours. 1N HCl and ethyl acetate were added to the reaction mixture and the organic layer was separated, washed with a saturated brine, dried over magnesium sulfate and concentrated in vacuo. The resulting residue was purified by column chromatography (NH-silica gel; hexane:ethyl acetate=4:1→3:2) to give the titled compound (39 mg). MS (m/z): 749 [M+H]+.

Aufarbeitung

  1. customthe organic layer was separated
  2. washwashed with a saturated brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified by column chromatography (NH-silica gel; hexane:ethyl acetate=4:1→3:2)

Quellen und Nachweise

ORD-Eintrag
ord-4ec9e9364d904c84ad2628ee503ff3ce
Quelldatensatz
uspto-grants-2011_12
Patentnummer
US08084611B2

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