Diisopropylethylamine → 3-Chloro-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-4-formyl-1H-pyrrole-2-carboxamide

HRID 1874958Notes

Reaction equation

HRID 1874958 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[Cl:25][C:26]1[C:30]([CH:31]=[O:32])=[CH:29][NH:28][C:27]=1[C:33]([OH:35])=O.[NH2:36][CH2:37][C:38]1[C:39]([F:55])=[C:40]([O:45][C:46]2[CH:47]=[C:48]([CH:51]=[C:52]([Cl:54])[CH:53]=2)[C:49]#[N:50])[C:41]([Cl:44])=[CH:42][CH:43]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:25][C:26]1[C:30]([CH:31]=[O:32])=[CH:29][NH:28][C:27]=1[C:33]([NH:36][CH2:37][C:38]1[CH:43]=[CH:42][C:41]([Cl:44])=[C:40]([O:45][C:46]2[CH:47]=[C:48]([C:49]#[N:50])[CH:51]=[C:52]([Cl:54])[CH:53]=2)[C:39]=1[F:55])=[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 866449013-Chloro-4-formyl-1H-pyrrole-2-carboxylic acid

Product 1

HCID 594515403-Chloro-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-4-formyl-1H-pyrrole-2-carboxamideYield 18.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HATU (0.061 g, 0.161 mmol) was added to a solution of 3-chloro-4-formyl-1H-pyrrole-2-carboxylic acid (0.028 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). The solution was stirred overnight at RT. The reaction mixture was partitioned between water and EtOAc, followed by washing the organic layer with a 15% Na2CO3 solution and drying over MgSO4. The solid was filtered off, and the solvent was evaporated. Purification was accomplished by silica gel column chromatography (EtOAc/hexanes) to give an orange film which was triturated in acetone to afford the title compound (0.014 g, 18%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.66 (br. s., 1H), 9.75 (s, 1H), 8.27 (t, 1H), 7.77-7.82 (m, 1H), 7.73 (s, 1H), 7.46-7.51 (m, 2H), 7.44 (t, 1H), 7.36 (t, 1H), 4.54 (d, 2H). LCMS: m/z=464.3 (M−1).

Workup

  1. customThe reaction mixture was partitioned between water and EtOAc
  2. washby washing the organic layer with a 15% Na2CO3 solution
  3. dry with materialdrying over MgSO4
  4. filtrationThe solid was filtered off
  5. customthe solvent was evaporated
  6. customPurification
  7. customto give an orange film which
  8. customwas triturated in acetone

Sources & evidence

ORD record
ord-fd9bcd0d6cb14d3088c90e4a1f266f9f
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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