Diisopropylethylamine → HCID 74222515, compound

HRID 2401645Notes

Reaction equation

HRID 2401645 reaction equation
[F:1][C:2]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:12]([C:16](O)=[O:17])=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=1.F[P-](F)(F)(F)(F)F.CN(C(ON1C2=NC=CC=C2N=N1)=[N+](C)C)C.C(N(CC)C(C)C)(C)C.Cl.[NH2:58][CH:59]([C:65]([F:68])([F:67])[F:66])[CH2:60][C:61]([O:63][CH3:64])=[O:62]>CN(C=O)C.O>[F:23][C:19]1[CH:20]=[CH:21][CH:22]=[C:2]([F:1])[C:3]=1[CH2:4][O:5][C:6]1[C:7]2[N:8]([C:12]([C:16]([NH:58][CH:59]([C:65]([F:66])([F:67])[F:68])[CH2:60][C:61]([O:63][CH3:64])=[O:62])=[O:17])=[C:13]([CH3:15])[N:14]=2)[CH:9]=[CH:10][CH:11]=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 44717682Methyl 3-amino-4,4,4-trifluorobutanoate--hydrogen chloride (1/1)HCID 867178728-((2,6-Difluorobenzyl)oxy)-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid

Product 1

HCID 74222515HCID 74222515, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

750 mg of 8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid Example 3A (2.36 mmol, 1 equivalent) were initially charged in 15 ml of DMF, and 2.24 g of N-[(dimethylamino)(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yloxy)methylidene]-N-methylmethanaminium hexafluorophosphate (HATU, 5.89 mmol, 2.5 equivalents) and 1.03 ml of N,N-diisopropylethylamine (0.76 g, 5.89 mmol, 2.5 equivalents) were added. The mixture was stirred at 60° C. for 20 min, 0.98 g of methyl 3-amino-4,4,4-trifluorobutanoate hydrochloride (Example 22A, 4.71 mmol, 2 equivalents) was added and the mixture was stirred at 60° C. overnight. The mixture was then added to 120 ml of water and stirred at RT for 30 min. The precipitated solid was filtered off, washed with 6 ml of diethyl ether and dried under reduced pressure. The residue was then concentrated on a silica gel column (mobile phases: dichloromethane/ethyl acetate 10:1). This gave 0.32 g (29% of theory) of the title compound.

Workup

  1. stirringthe mixture was stirred at 60° C. overnight
  2. stirringstirred at RT for 30 min
  3. filtrationThe precipitated solid was filtered off
  4. washwashed with 6 ml of diethyl ether
  5. customdried under reduced pressure
  6. concentrationThe residue was then concentrated on a silica gel column (mobile phases: dichloromethane/ethyl acetate 10:1)

Sources & evidence

ORD record
ord-5469882104de450c89b161ee5149e9cb
Source dataset
uspto-grants-2014_08
Patent number
US08796305B2

Reaction notes

Loading…