4-Methylmorpholine → rac-tert-Butyl {1-[({8-[(2,6-difluorobenzyl)oxy]-2,6-dimethylimidazo[1,2-a]pyridin-3-yl}-carbonyl)amino]-3-methylbutan-2-yl}carbamate

HRID 2275843Notes

Reaction equation

HRID 2275843 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:13]([C:17]([OH:19])=O)=[C:14]([CH3:16])[N:15]=2)[CH:9]=[C:10]([CH3:12])[CH:11]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[NH2:56][CH2:57][CH:58]([NH:62][C:63](=[O:69])[O:64][C:65]([CH3:68])([CH3:67])[CH3:66])[CH:59]([CH3:61])[CH3:60].O.C(O)(C(F)(F)F)=O>CN(C=O)C>[F:1][C:2]1[CH:23]=[CH:22][CH:21]=[C:20]([F:24])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:13]([C:17]([NH:56][CH2:57][CH:58]([NH:62][C:63](=[O:69])[O:64][C:65]([CH3:66])([CH3:68])[CH3:67])[CH:59]([CH3:61])[CH3:60])=[O:19])=[C:14]([CH3:16])[N:15]=2)[CH:9]=[C:10]([CH3:12])[CH:11]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 22392675Trifluoroacetic acid waterHCID 22664672tert-butyl N-(1-amino-3-methylbutan-2-yl)carbamateHCID 867178848-[(2,6-Difluorobenzyl)oxy]-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylic acid

Product 1

HCID 90135994rac-tert-Butyl {1-[({8-[(2,6-difluorobenzyl)oxy]-2,6-dimethylimidazo[1,2-a]pyridin-3-yl}-carbonyl)amino]-3-methylbutan-2-yl}carbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

200 mg (0.60 mmol) of 8-[(2,6-difluorobenzyl)oxy]-2,6-dimethylimidazo[1,2-a]pyridine-3-carboxylic acid from Example 21A, 203 mg (0.63 mmol) of HATU and 0.20 ml (1.81 mmol) of 4-methylmorpholine were initially charged in DMF (3.8 ml), the mixture was stirred at RT for 20 min, 134 mg (0.66 mmol) of rac-tert-butyl (1-amino-3-methylbutan-2-yl)carbamate were added and the reaction mixture was stirred at RT overnight. Water/TFA were added and the mixture was purified by preparative RP-HPLC (acetonitrile/water gradient with addition of 0.1% TFA). The product fractions were concentrated and the residue was taken up in dichloromethane and washed twice with saturated aqueous sodium bicarbonate solution. The aqueous phase was extracted twice with dichloromethane and the combined organic phases were dried over sodium sulphate, filtered off and concentrated. This gave 262 mg (84% of theory, purity 100%) of the target compound.

Workup

  1. stirringthe reaction mixture was stirred at RT overnight
  2. customthe mixture was purified by preparative RP-HPLC (acetonitrile/water gradient with addition of 0.1% TFA)
  3. concentrationThe product fractions were concentrated
  4. washwashed twice with saturated aqueous sodium bicarbonate solution
  5. extractionThe aqueous phase was extracted twice with dichloromethane
  6. dry with materialthe combined organic phases were dried over sodium sulphate
  7. filtrationfiltered off
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-3d720566bb8f4af080f9ade0b9b5fb6e
Source dataset
uspto-grants-2015_09
Patent number
US09126998B2

Reaction notes

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