Pyrrole-2-Carboxylic Acid → N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-N-ethyl-1H-pyrrole-2-carboxamide

HRID 1875091Notes

Reaction equation

HRID 1875091 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]=[CH:59][CH:58]=[C:57]1[C:61]([OH:63])=O.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:57]2[NH:56][CH:60]=[CH:59][CH:58]=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 12473Pyrrole-2-Carboxylic AcidHCID 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)benzonitrile

Product 1

HCID 59451422N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-N-ethyl-1H-pyrrole-2-carboxamideYield 31.1%

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-pyrrole-2-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 (0.039 g, 31%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.51 (s, 1H), 7.82 (br. s., 1H), 7.08-7.68 (m, 3H), 6.74-7.04 (m, 1H), 6.24-6.62 (m, 1H), 6.12 (d, 1H), 4.56-5.10 (m, 2H), 3.54-3.88 (m, 2H), 0.96-1.45 (m, 3H). LCMS m/z 433.9 (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-feaff71bf0e04c88b1e0dc38f6913213
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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