Diisopropylethylamine → rac-8-[(3,3-Difluorocyclobutyl)methoxy]-2,6-dimethyl-N-(7,7,7-trifluoro-2-hydroxy-2-methylheptan-3-yl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 1844223Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1844223
[F:1][C:2]1([F:22])[CH2:5][CH:4]([CH2:6][O:7][C:8]2[C:9]3[N:10]([C:15]([C:19]([OH:21])=O)=[C:16]([CH3:18])[N:17]=3)[CH:11]=[C:12]([CH3:14])[CH:13]=2)[CH2:3]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.Cl.[NH2:57][CH:58]([CH2:63][CH2:64][CH2:65][C:66]([F:69])([F:68])[F:67])[C:59]([CH3:62])([OH:61])[CH3:60]>CN(C=O)C.O>[F:1][C:2]1([F:22])[CH2:5][CH:4]([CH2:6][O:7][C:8]2[C:9]3[N:10]([C:15]([C:19]([NH:57][CH:58]([CH2:63][CH2:64][CH2:65][C:66]([F:67])([F:68])[F:69])[C:59]([OH:61])([CH3:62])[CH3:60])=[O:21])=[C:16]([CH3:18])[N:17]=3)[CH:11]=[C:12]([CH3:14])[CH:13]=2)[CH2:3]1

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86718188rac-3-Amino-7,7,7-trifluoro-2-methylheptan-2-ol hydrochlorideHCID 867181928-[(3,3-Difluorocyclobutyl)methoxy]-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylic acid

Produkt 1

HCID 90115706rac-8-[(3,3-Difluorocyclobutyl)methoxy]-2,6-dimethyl-N-(7,7,7-trifluoro-2-hydroxy-2-methylheptan-3-yl)imidazo[1,2-a]pyridine-3-carboxamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

100 mg (0.32 mmol) of 8-[(3,3-difluorocyclobutyl)methoxy]-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylic acid Example 107A and 135 mg (0.35 mmol) of HATU were initially charged in 2 ml of DMF. 0.16 ml (0.96 mmol) of N,N-diisopropylethylamine and 70.6 mg (0.354 mmol) of rac-3-amino-7,7,7-trifluoro-2-methylheptan-2-ol hydrochloride Example 103A were then added, and the mixture was stirred at RT overnight. 7 ml of water were added, and the reaction solution was extracted twice with 15 ml of ethyl acetate. The combined organic phases were washed with 15 ml of water and with 10 ml of saturated aqueous sodium chloride solution, dried over magnesium sulphate, filtered and concentrated. The residue was purified by preparative RP-HPLC (acetonitrile-water+0.1% formic acid) and the product fractions were combined and concentrated to dryness. This gave 86 mg of the target compound (55% of theory).

Aufarbeitung

  1. extractionthe reaction solution was extracted twice with 15 ml of ethyl acetate
  2. washThe combined organic phases were washed with 15 ml of water and with 10 ml of saturated aqueous sodium chloride solution
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by preparative RP-HPLC (acetonitrile-water+0.1% formic acid)
  7. concentrationconcentrated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-0eeb58d2b7fb46169e7d780f3bbd3044
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08946215B2

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