Diisopropylethylamine → HCID 90114495, compound

HRID 2275896Notes

Reaction equation

HRID 2275896 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.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.[CH3:57][O:58][CH2:59][C:60]([CH3:64])([NH2:63])[CH2:61][NH2:62]>CN(C=O)C.O.C(O)(C(F)(F)F)=O>[NH2:63][C:60]([CH3:64])([CH2:59][O:58][CH3:57])[CH2:61][NH:62][C:16]([C:12]1[N:8]2[CH:9]=[CH:10][CH:11]=[C:6]([O:5][CH2:4][C:3]3[C:19]([F:23])=[CH:20][CH:21]=[CH:22][C:2]=3[F:1])[C:7]2=[N:14][C:13]=1[CH3:15])=[O:17]

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 545933941248944-55-9HCID 867178728-((2,6-Difluorobenzyl)oxy)-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid

Product 1

HCID 90114495HCID 90114495, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 22392675Trifluoroacetic acid waterSolvent

Procedure

180 mg (0.57 mmol) of 8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid Example 3A, 237 mg (0.62 mmol) of HATU and 0.30 ml (1.70 mmol) of N,N-diisopropylethylamine were initially charged in 3.6 ml of DMF, and the mixture was stirred at RT for 20 min. 74 mg (0.62 mmol) of rac-3-methoxy-2-methylpropane-1,2-diamine were then added and the reaction mixture was stirred at RT overnight. The reaction solution was diluted with water/TFA and purified by preparative RP-HPLC (acetonitrile/water gradient with addition of 0.1% TFA). The product fraction was concentrated. 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 and concentrated. This gave 136 mg (56% of theory, purity 98%) of the title compound.

Workup

  1. stirringthe reaction mixture was stirred at RT overnight
  2. custompurified by preparative RP-HPLC (acetonitrile/water gradient with addition of 0.1% TFA)
  3. concentrationThe product fraction was 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
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-30462cc232c74e4aadc95479d2a004fa
Source dataset
uspto-grants-2015_09
Patent number
US09126998B2

Reaction notes

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