Diisopropylethylamine → HCID 90114624, compound

HRID 2275895Notes

Reaction equation

HRID 2275895 reaction equation
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.[F:34][C:35]1[CH:55]=[CH:54][CH:53]=[C:52]([F:56])[C:36]=1[CH2:37][O:38][C:39]1[C:40]2[N:41]([C:45]([C:49]([OH:51])=O)=[C:46]([CH3:48])[N:47]=2)[CH:42]=[CH:43][CH:44]=1.Cl.Cl.[CH:59]([O:62][CH2:63][CH:64]([NH2:67])[CH2:65][NH2:66])([CH3:61])[CH3:60]>CN(C=O)C.O.C(O)(C(F)(F)F)=O>[NH2:67][CH:64]([CH2:63][O:62][CH:59]([CH3:61])[CH3:60])[CH2:65][NH:66][C:49]([C:45]1[N:41]2[CH:42]=[CH:43][CH:44]=[C:39]([O:38][CH2:37][C:36]3[C:35]([F:34])=[CH:55][CH:54]=[CH:53][C:52]=3[F:56])[C:40]2=[N:47][C:46]=1[CH3:48])=[O:51]

Participants

7

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 867178728-((2,6-Difluorobenzyl)oxy)-2-methylimidazo[1,2-a]pyridine-3-carboxylic acidHCID 90114173HCID 90114173, compound

Product 1

HCID 90114624HCID 90114624, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 22392675Trifluoroacetic acid waterSolvent

Procedure

125 mg (0.33 mmol) of HATU and 0.16 ml (0.90 mmol) of N,N-diisopropylethylamine were added to 95 mg (0.30 mmol) of 8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid Example 3A in DMF (1.9 ml), and the mixture was stirred at RT for 20 min. At −20° C., 145 mg (0.54 mmol, 76% pure) of rac-3-isopropoxypropane-1,2-diamine dihydrochloride Example 224A in DMF (0.5 ml), to which 0.31 ml (1.8 mmol) of N,N-diisopropylethylamine had been added beforehand and which had been stirred at RT for 10 min, were then slowly added dropwise to the reaction mixture. The mixture was stirred at RT overnight. The mixture was then diluted with water/TFA and purified by prep. RP-HPLC (acetonitrile/water gradient with addition of 0.1% TFA). The product fraction was concentrated and then re-purified by thick-layer chromatography (dichloromethane/methanol: 10:1). This gave 15 mg (12% of theory) of the target compound.

Workup

  1. stirringhad been stirred at RT for 10 min
  2. additionwere then slowly added dropwise to the reaction mixture
  3. stirringThe mixture was stirred at RT overnight
  4. custompurified by prep
  5. additionRP-HPLC (acetonitrile/water gradient with addition of 0.1% TFA)
  6. concentrationThe product fraction was concentrated
  7. customre-purified by thick-layer chromatography (dichloromethane/methanol: 10:1)

Sources & evidence

ORD record
ord-b58cf17ddf9f407493e15fe3f93092c1
Source dataset
uspto-grants-2015_09
Patent number
US09126998B2

Reaction notes

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