Diisopropylethylamine → N-[(2R)-1-Hydroxyhexan-2-yl]-2,6-dimethyl-8-[4,4,4-trifluoro-3-(trifluoromethyl)butoxy]imidazo-[1,2-a]pyridine-3-carboxamide

HRID 1844220Notes

Reaction equation

HRID 1844220 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]2[C:9]([O:10][CH2:11][CH2:12][CH:13]([C:18]([F:21])([F:20])[F:19])[C:14]([F:17])([F:16])[F:15])=[CH:8][C:7]([CH3:22])=[CH:6][N:5]2[C:23]=1[C:24]([OH:26])=O.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.[NH2:60][C@H:61]([CH2:64][CH2:65][CH2:66][CH3:67])[CH2:62][OH:63]>CN(C=O)C.O>[OH:63][CH2:62][C@H:61]([NH:60][C:24]([C:23]1[N:5]2[CH:6]=[C:7]([CH3:22])[CH:8]=[C:9]([O:10][CH2:11][CH2:12][CH:13]([C:14]([F:16])([F:15])[F:17])[C:18]([F:19])([F:20])[F:21])[C:4]2=[N:3][C:2]=1[CH3:1])=[O:26])[CH2:64][CH2:65][CH2:66][CH3:67]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 6994402(R)-2-Aminohexan-1-olHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86717934HCID 86717934, compound

Product 1

HCID 74222629N-[(2R)-1-Hydroxyhexan-2-yl]-2,6-dimethyl-8-[4,4,4-trifluoro-3-(trifluoromethyl)butoxy]imidazo-[1,2-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

150 mg (0.39 mmol) of 2,6-dimethyl-8-[4,4,4-trifluoro-3-(trifluoromethyl)butoxy]imidazo[1,2-a]-pyridine-3-carboxylic acid Example 91A and 163 mg (0.43 mmol) of HATU were initially charged in 2.5 ml of DMF. 0.2 ml (1.17 mmol) of N,N-diisopropylethylamine and 50.3 mg (0.43 mmol) of (R)-(−)-2-amino-1-hexanol were then added, and the mixture was stirred at RT overnight. 10 ml of water were added, the reaction solution was extracted twice with 20 ml of ethyl acetate and the combined organic phases were washed with 20 ml of water and with 20 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), the product fractions were combined and concentrated to dryness and the residue was dissolved in a mixture of 1.5 ml of tert-butanol and 2 ml of water and lyophilized overnight. This gave 42 mg of the target compound (95% pure, 21% of theory).

Workup

  1. extractionthe reaction solution was extracted twice with 20 ml of ethyl acetate
  2. washthe combined organic phases were washed with 20 ml of water and with 20 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
  8. dissolutionthe residue was dissolved in a mixture of 1.5 ml of tert-butanol and 2 ml of water
  9. waitlyophilized overnight

Sources & evidence

ORD record
ord-5f5cb9472bfe4e0cb79f933553b11015
Source dataset
uspto-grants-2015_02
Patent number
US08946215B2

Reaction notes

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