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

HRID 1874975Notes

Reaction equation

HRID 1874975 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]=[C:49]([CH2:51][CH2:52][OH:53])[NH:48][C:47]=1[C:54](O)=[O:55].CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:45][C:46]1[CH:50]=[C:49]([CH2:51][CH2:52][OH:53])[NH:48][C:47]=1[C:54]([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:55]

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 684839683-chloro-5-(2-hydroxyethyl)-1H-pyrrole-2-carboxylic acid

Product 1

HCID 594514823-Chloro-N-({4-chloro-3-[(3-chloro-5-cyanophenyl)oxy]-2-fluorophenyl}methyl)-5-(2-hydroxyethyl)-1H-pyrrole-2-carboxamideYield 2.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HATU (0.057 g, 0.15 mmol) was added to a solution of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.047 g, 0.15 mmol), 3-chloro-5-(2-hydroxyethyl)-1H-pyrrole-2-carboxylic acid (0.028 g, 0.15 mmol) and DIPEA (0.026 mL, 0.150 mmol) in DMF (2 mL). The resulting solution was stirred for 2 hours then partitioned between water and EtOAc. The organic layer was separated, dried over MgSO4 and evaporated to a residue. The residue was purified by reverse-phase HPLC (water/acetonitrile with 0.1% TFA) to afford the title compound (0.0016 g, 2%) as a film. 1H NMR (400 MHz, Acetone-d6) δ ppm 7.60-7.68 (m, 1H), 7.48-7.53 (m, 1H), 7.41-7.45 (m, 2H), 7.37-7.40 (m, 2H), 6.03 (d, 1H), 4.69 (d, 2H), 3.78 (t, 2 H), 2.82 (t, 2H). LCMS: m/z=479.9 (M−1).

Workup

  1. customthen partitioned between water and EtOAc
  2. customThe organic layer was separated
  3. dry with materialdried over MgSO4
  4. customevaporated to a residue
  5. customThe residue was purified by reverse-phase HPLC (water/acetonitrile with 0.1% TFA)

Sources & evidence

ORD record
ord-925df0716aec4937ab03e639b5ed807c
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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