Diisopropylethylamine → 3-Chloro-N2-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-pyrrole-2,5-dicarboxamide

HRID 1874969Notes

Reaction equation

HRID 1874969 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:25][C:26]([C:28]1[NH:32][C:31]([C:33]([OH:35])=O)=[C:30]([Cl:36])[CH:29]=1)=[O:27].[NH2:37][CH2:38][C:39]1[C:40]([F:56])=[C:41]([O:46][C:47]2[CH:48]=[C:49]([CH:52]=[C:53]([Cl:55])[CH:54]=2)[C:50]#[N:51])[C:42]([Cl:45])=[CH:43][CH:44]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:36][C:30]1[CH:29]=[C:28]([C:26]([NH2:25])=[O:27])[NH:32][C:31]=1[C:33]([NH:37][CH2:38][C:39]1[CH:44]=[CH:43][C:42]([Cl:45])=[C:41]([O:46][C:47]2[CH:48]=[C:49]([C:50]#[N:51])[CH:52]=[C:53]([Cl:55])[CH:54]=2)[C:40]=1[F:56])=[O:35]

Participants

6

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 594513923-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrileHCID 684804915-(Aminocarbonyl)-3-chloro-1H-pyrrole-2-carboxylic acid

Product 1

HCID 594513903-Chloro-N2-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-pyrrole-2,5-dicarboxamideYield 29.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HATU (0.061 g, 0.161 mmol) was added to a solution of 5-(aminocarbonyl)-3-chloro-1H-pyrrole-2-carboxylic acid (0.030 g, 0.161 mmol), 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.050 g, 0.161 mmol), and DIPEA (0.028 mL, 0.161 mmol) in DMF (2 mL). This solution was stirred overnight at RT. The reaction mixture was partitioned between water and EtOAc. The organic layer was washed with a 15% solution of Na2CO3, dried over MgSO4, filtered and evaporated. Purification was accomplished by silica gel column chromatography (EtOAc/hexanes) to afford the title compound (0.023 g, 28%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.08 (br. s., 1H), 8.48-8.74 (m, 1H), 7.72-7.98 (m, 2H), 7.27-7.62 (m, 5H), 6.83 (d, 1H), 4.48 (d, 2H). LCMS: m/z 481.0 (M+1).

Workup

  1. customThe reaction mixture was partitioned between water and EtOAc
  2. washThe organic layer was washed with a 15% solution of Na2CO3
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. customPurification

Sources & evidence

ORD record
ord-f07daf14a82840e78108f34000ba7c72
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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