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 1844223Notes

Reaction equation

HRID 1844223 reaction equation
[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

Participants

7

Reactant 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

Product 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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-0eeb58d2b7fb46169e7d780f3bbd3044
Source dataset
uspto-grants-2015_02
Patent number
US08946215B2

Reaction notes

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