Diisopropylethylamine → tert-butyl 1-((3,5-difluoro-4-(1-methoxy-2-methylpropan-2-yl)phenyl)carbamoyl)-6-ethoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 2202272Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2202272
C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.[C:19]([O:23][C:24]([N:26]1[CH2:35][CH2:34][C:33]2[C:28](=[CH:29][CH:30]=[C:31]([O:36][CH2:37][CH3:38])[CH:32]=2)[CH:27]1[C:39]([OH:41])=O)=[O:25])([CH3:22])([CH3:21])[CH3:20].[F:42][C:43]1[CH:44]=[C:45]([CH:47]=[C:48]([F:56])[C:49]=1[C:50]([CH3:55])([CH3:54])[CH2:51][O:52][CH3:53])[NH2:46].CCN(C(C)C)C(C)C>CN(C1C=CN=CC=1)C.C(OCC)(=O)C.O>[F:42][C:43]1[CH:44]=[C:45]([NH:46][C:39]([CH:27]2[C:28]3[C:33](=[CH:32][C:31]([O:36][CH2:37][CH3:38])=[CH:30][CH:29]=3)[CH2:34][CH2:35][N:26]2[C:24]([O:23][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:25])=[O:41])[CH:47]=[C:48]([F:56])[C:49]=1[C:50]([CH3:54])([CH3:55])[CH2:51][O:52][CH3:53]

Komponenten

8

Edukt 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 1186226932-(Tert-butoxycarbonyl)-6-ethoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acidHCID 1186228033,5-Difluoro-4-(1-methoxy-2-methylpropan-2-yl)aniline

Produkt 1

HCID 118622717tert-butyl 1-((3,5-difluoro-4-(1-methoxy-2-methylpropan-2-yl)phenyl)carbamoyl)-6-ethoxy-3,4-dihydroisoquinoline-2(1H)-carboxylateAusbeute 82 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

T3P (9.88 mL, 16.80 mmol) was added to a solution of 2-(tert-butoxycarbonyl)-6-ethoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid (1.8 g, 5.60 mmol), 3,5-difluoro-4-(1-methoxy-2-methylpropan-2-yl)aniline (1.206 g, 5.60 mmol), DIEA (4.89 mL, 28.01 mmol) and DMAP (0.684 g, 5.60 mmol) in ethyl acetate (5 mL), and the mixture was stirred overnight at 60° C. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with 10% aqueous citric acid solution, aqueous sodium hydrogencarbonate solution and brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (solvent gradient; 3→50% ethyl acetate/hexane) to give tert-butyl 1-((3,5-difluoro-4-(1-methoxy-2-methylpropan-2-yl)phenyl)carbamoyl)-6-ethoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate (2.380 g, 4.59 mmol, 82%) as a white solid.

Aufarbeitung

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with 10% aqueous citric acid solution, aqueous sodium hydrogencarbonate solution and brine
  3. dry with materialdried over magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (solvent gradient; 3→50% ethyl acetate/hexane)

Quellen und Nachweise

ORD-Eintrag
ord-12621204e001486ab13651f53a115d3d
Quelldatensatz
uspto-grants-2016_06
Patentnummer
US09365520B2

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