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

HRID 2275842Notes

Reaction equation

HRID 2275842 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([O:15][CH2:16][C:17]2[C:22]([F:23])=[CH:21][CH:20]=[CH:19][C:18]=2[F:24])[C:5]2[N:6]([C:8]([C:12](O)=[O:13])=[C:9]([CH3:11])[N:10]=2)[CH:7]=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>[Cl:1][C:2]1[CH:3]=[C:4]([O:15][CH2:16][C:17]2[C:18]([F:24])=[CH:19][CH:20]=[CH:21][C:22]=2[F:23])[C:5]2[N:6]([C:8]([C:12]([NH:56][CH2:57][CH:58]([NH:62][C:63](=[O:69])[O:64][C:65]([CH3:67])([CH3:66])[CH3:68])[CH:59]([CH3:61])[CH3:60])=[O:13])=[C:9]([CH3:11])[N:10]=2)[CH:7]=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 867178796-Chloro-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid

Product 1

HCID 86717985rac-tert-Butyl {1-[({6-chloro-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridin-3-yl}-carbonyl)amino]-3-methylbutan-2-yl}carbamate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

200 mg (0.57 mmol) of 6-chloro-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid Example 16A, 191 mg (0.60 mmol) of HATU and 0.19 ml (1.70 mmol) of 4-methylmorpholine in DMF (3.6 ml) were stirred at RT for 20 min. 126 mg (0.62 mmol) of rac-tert-butyl (1-amino-3-methylbutan-2-yl)carbamate were then added and the reaction mixture was stirred at RT overnight. Water/TFA were then 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 264 mg (87% of theory, purity 100%) of the target compound.

Workup

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

Sources & evidence

ORD record
ord-49f6495078ee4af8a348ff28a64f1273
Source dataset
uspto-grants-2015_09
Patent number
US09126998B2

Reaction notes

Loading…