4-Methylmorpholine → N-Cyclopropyl-6-[(1E)-3-oxo-3-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}amino)-prop-1-en-1-yl]-4-(trifluoromethyl)nicotinamide

HRID 339121

Reaktionsgleichung

Reaktionsgleichung von HRID 339121
[CH:1]1([NH:4][C:5]([C:7]2[C:8]([C:18]([F:21])([F:20])[F:19])=[CH:9][C:10](/[CH:13]=[CH:14]/[C:15]([OH:17])=O)=[N:11][CH:12]=2)=[O:6])[CH2:3][CH2:2]1.[F:22][C:23]([F:37])([F:36])[CH:24]([C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:34])[F:33])[CH:27]=1)[NH2:25].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>CN(C)C=O>[CH:1]1([NH:4][C:5](=[O:6])[C:7]2[C:8]([C:18]([F:21])([F:20])[F:19])=[CH:9][C:10](/[CH:13]=[CH:14]/[C:15](=[O:17])[NH:25][CH:24]([C:26]3[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:33])([F:34])[F:35])[CH:27]=3)[C:23]([F:37])([F:36])[F:22])=[N:11][CH:12]=2)[CH2:2][CH2:3]1

Komponenten

6

Edukt 4

HCID 79724-MethylmorpholineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 438251722,2,2-Trifluoro-1-(3-(trifluoromethyl)phenyl)ethanamineHCID 58247954(2E)-3-[5-(Cyclopropylcarbamoyl)-4-(trifluoromethyl)pyridin-2-yl]acrylic acid

Produkt 1

HCID 58247982N-Cyclopropyl-6-[(1E)-3-oxo-3-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}amino)-prop-1-en-1-yl]-4-(trifluoromethyl)nicotinamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

(2E)-3-[5-(Cyclopropylcarbamoyl)-4-(trifluoromethyl)pyridin-2-yl]acrylic acid (61 mg, 0.20 mmol) and 2,2,2-trifluoro-1-[3-trifluoromethylphenyl]ethanamine (46 mg, 0.19 mmol) were initially charged in N,N-dimethylformamide and admixed with HBTU (72 mg, 0.19 mmol) and N-methylmorpholine (57 mg, 0.57 mmol) and stirred at room temperature overnight. Subsequently, the reaction mixture was concentrated under reduced pressure, taken up in ethyl acetate and washed successively with a sodium hydrogencarbonate solution (10%) and a saturated sodium chloride solution. The organic phase was dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was chromatographed on a preparative HPLC with water/acetonitrile as the eluent (gradient=43 min from 10% acetonitrile in water to 100% acetonitrile).

Aufarbeitung

  1. concentrationSubsequently, the reaction mixture was concentrated under reduced pressure
  2. washwashed successively with a sodium hydrogencarbonate solution (10%)
  3. dry with materialThe organic phase was dried over sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was chromatographed on a preparative HPLC with water/acetonitrile as the eluent (gradient=43 min from 10% acetonitrile in water to 100% acetonitrile)

Quellen und Nachweise

ORD-Eintrag
ord-28224d6995934df28f8a1a255c112436
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08889878B2

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