Diisopropylethylamine → HCID 178463700, compound

HRID 1875092Notes

Reaction equation

HRID 1875092 reaction equation
CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl:34][C:35]1[CH:36]=[C:37]([CH:40]=[C:41]([O:43][C:44]2[C:49]([Cl:50])=[CH:48][CH:47]=[C:46]([CH2:51][NH:52][CH2:53][CH3:54])[C:45]=2[F:55])[CH:42]=1)[C:38]#[N:39].[NH:56]1[CH:60]=[C:59]([C:61]([OH:63])=O)[N:58]=[CH:57]1.C([O-])(O)=O.[Na+]>C(OCC)(=O)C.CN(C=O)C>[Cl:50][C:49]1[CH:48]=[CH:47][C:46]([CH2:51][N:52]([CH2:53][CH3:54])[C:61]([C:59]2[N:58]=[CH:57][NH:56][CH:60]=2)=[O:63])=[C:45]([F:55])[C:44]=1[O:43][C:41]1[CH:40]=[C:37]([C:38]#[N:39])[CH:36]=[C:35]([Cl:34])[CH:42]=1

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 684856043-Chloro-5-({6-chloro-3-[(ethylamino)methyl]-2-fluorophenyl}oxy)benzonitrileHCID 178524800HCID 178524800, compound

Product 1

HCID 178463700HCID 178463700, compoundYield 36.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

DMF (3 mL) and DIPEA (0.1 mL, 0.59 mmol) were added to a mixture of HATU (0.12 g, 0.32 mmol), 3-chloro-5-({6-chloro-3-[(ethylamino)methyl]-2-fluorophenyl}oxy)benzonitrile (0.10 g, 0.29 mmol) and 1H-imidazole-4-carboxylic acid (0.05 g, 0.41 mmol). The yellow solution was stirred at RT under a nitrogen atmosphere for 48 h then ethyl acetate (100 ml) and saturated NaHCO3 solution (100 ml) were added. The organic layer was washed with saturated NaHCO3 solution (2×100 ml), brine (150 mL), dried over MgSO4, filtered and concentrated. The crude material was purified by Reverse Phase HPLC (MeCN/water+0.1% TFA) to give the title compound (0.046 g, 36%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.47-8.80 (m, 1H), 7.89-8.03 (m, 1H), 7.82 (s, 1H), 7.44-7.56 (m, 3H), 7.33 (t, 1H), 4.69-5.18 (m, 2H), 3.33-3.79 (m, 2H), 1.01-1.27 (m, 3H). LCMS m/z 431.2 (M−H).

Workup

  1. washThe organic layer was washed with saturated NaHCO3 solution (2×100 ml), brine (150 mL)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude material was purified by Reverse Phase HPLC (MeCN/water+0.1% TFA)

Sources & evidence

ORD record
ord-fa73010c116c404d9860d5521e927b21
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

Loading…