Trifluoroacetic acid → Methyl 6,6,6-trifluoro-N-({8-[(3-fluoropyridin-2-yl)methoxy]-2,6-dimethylimidazo[1,2-a]pyridin-3-yl}carbonyl)-5-hydroxynorleucinate

HRID 1844200Notes

Reaction equation

HRID 1844200 reaction equation
Cl.[F:2][C:3]1[C:4]([CH2:9][O:10][C:11]2[C:12]3[N:13]([C:18]([C:22](O)=[O:23])=[C:19]([CH3:21])[N:20]=3)[CH:14]=[C:15]([CH3:17])[CH:16]=2)=[N:5][CH:6]=[CH:7][CH:8]=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.[F:59][C:60]([F:72])([F:71])[CH:61]([OH:70])[CH2:62][CH2:63][C@@H:64]([C:66]([O:68][CH3:69])=[O:67])[NH2:65].C(O)(C(F)(F)F)=O>CN(C=O)C.O>[F:59][C:60]([F:71])([F:72])[CH:61]([OH:70])[CH2:62][CH2:63][C@@H:64]([C:66]([O:68][CH3:69])=[O:67])[NH:65][C:22]([C:18]1[N:13]2[CH:14]=[C:15]([CH3:17])[CH:16]=[C:11]([O:10][CH2:9][C:4]3[C:3]([F:2])=[CH:8][CH:7]=[CH:6][N:5]=3)[C:12]2=[N:20][C:19]=1[CH3:21])=[O:23]

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 867182148-[(3-Fluoropyridin-2-yl)methoxy]-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylic acid hydrochlorideHCID 86718222Methyl 6,6,6-trifluoro-5-hydroxynorleucinate hydrochloride

Product 1

HCID 86718221Methyl 6,6,6-trifluoro-N-({8-[(3-fluoropyridin-2-yl)methoxy]-2,6-dimethylimidazo[1,2-a]pyridin-3-yl}carbonyl)-5-hydroxynorleucinate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

250 mg (0.71 mmol) of 8-[(3-fluoropyridin-2-yl)methoxy]-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylic acid hydrochloride from Example 121A, 299 mg (0.79 mmol) of HATU and 0.50 ml (2.85 mmol) of N,N-diisopropylethylamine were initially charged in 2.5 ml of DMF, and the mixture was stirred at RT for 20 min. 216 mg (0.86 mmol) of methyl 6,6,6-trifluoro-5-hydroxynorleucinate hydrochloride (stereoisomer mixture) were added, and the mixture was stirred at RT overnight. Water and TFA were added to the reaction solution and the product was purified by preparative RP-HPLC (acetonitrile/water gradient with addition of 0.1% TFA). The product fractions were concentrated, sodium bicarbonate solution was added to the residue and the mixture was extracted three times with dichloromethane. The combined organic phases were dried over sodium sulphate, filtered off, concentrated and dried under high vacuum. This gave 265 mg (69% of theory) of the target compound.

Workup

  1. stirringthe mixture was stirred at RT overnight
  2. customthe product was purified by preparative RP-HPLC (acetonitrile/water gradient with addition of 0.1% TFA)
  3. concentrationThe product fractions were concentrated
  4. additionsodium bicarbonate solution was added to the residue
  5. extractionthe mixture was extracted three times with dichloromethane
  6. dry with materialThe combined organic phases were dried over sodium sulphate
  7. filtrationfiltered off
  8. concentrationconcentrated
  9. customdried under high vacuum

Sources & evidence

ORD record
ord-0cd4c8b60ecf4633812e7ae13e0c71ea
Source dataset
uspto-grants-2015_02
Patent number
US08946215B2

Reaction notes

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