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

HRID 1874844Notes

Reaction equation

HRID 1874844 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:25][CH2:26][C:27]1[C:28]([F:44])=[C:29]([O:34][C:35]2[CH:36]=[C:37]([CH:40]=[C:41]([Cl:43])[CH:42]=2)[C:38]#[N:39])[C:30]([Cl:33])=[CH:31][CH:32]=1.[Cl:45][C:46]1[CH:50]=[CH:49][NH:48][C:47]=1[C:51](O)=[O:52].CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:45][C:46]1[CH:50]=[CH:49][NH:48][C:47]=1[C:51]([NH:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[C:29]([O:34][C:35]2[CH:36]=[C:37]([C:38]#[N:39])[CH:40]=[C:41]([Cl:43])[CH:42]=2)[C:28]=1[F:44])=[O:52]

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 221800183-chloro-1H-pyrrole-2-carboxylic acidHCID 594513923-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile

Product 1

HCID 251254673-chloro-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-1H-pyrrole-2-carboxamideYield 26.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

HATU (0.061 g, 0.16 mmole) was added to a DMF (2 ml) solution of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.050 g, 0.16 mmole) and 3-chloro-1H-pyrrole-2-carboxylic acid (0.023 g, 0.16 mmole) in DMF. DIPEA (0.021 g, 0.16 mmole) was added and the solution stirred for 2 h. The mixture was partitioned between EtOAc and water. The organic layer was separated and washed with 15% NaHCO3 and dried over MgSO4 and the EtOAc evaporated. The residue was purified on silica with EtOAc and Hexanes to afford the title compound (0.0187 g, 26%) as a white solid. 1H NMR (400 MHz, Acetone-d6): δ ppm 10.93 (br. s., 1H), 7.62-7.67 (m, 1H), 7.56-7.62 (m, 1H), 7.37-7.48 (m, 4H), 7.02 (t, 1H), 6.23 (t, 1H), 4.72 (d, 2H). MS: m/z 438.1 (M+1).

Workup

  1. customThe mixture was partitioned between EtOAc and water
  2. customThe organic layer was separated
  3. washwashed with 15% NaHCO3
  4. dry with materialdried over MgSO4
  5. customthe EtOAc evaporated
  6. customThe residue was purified on silica with EtOAc and Hexanes

Sources & evidence

ORD record
ord-d39303d8ec5b4134ba5d287652712e5c
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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