Diisopropylethylamine → 4-chloro-N-{[4-chloro-2-fluoro-3-(1-naphthalenyloxy)phenyl]methyl}-2-ethyl-1H-imidazole-5-carboxamide

HRID 1875050Notes

Reaction equation

HRID 1875050 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[CH:31]=[CH:30][C:29]([CH2:32][NH2:33])=[C:28]([F:34])[C:27]=1[O:35][C:36]1[C:45]2[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=2)[CH:39]=[CH:38][CH:37]=1.[Cl:46][C:47]1[N:48]=[C:49]([CH2:55][CH3:56])[NH:50][C:51]=1[C:52](O)=[O:53].C(N(C(C)C)CC)(C)C>CN(C=O)C>[Cl:46][C:47]1[N:48]=[C:49]([CH2:55][CH3:56])[NH:50][C:51]=1[C:52]([NH:33][CH2:32][C:29]1[CH:30]=[CH:31][C:26]([Cl:25])=[C:27]([O:35][C:36]2[C:45]3[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=3)[CH:39]=[CH:38][CH:37]=2)[C:28]=1[F:34])=[O:53]

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 68486009{[4-Chloro-2-fluoro-3-(1-naphthalenyloxy)phenyl]methyl}amineHCID 178437661HCID 178437661, compound

Product 1

HCID 1784376534-chloro-N-{[4-chloro-2-fluoro-3-(1-naphthalenyloxy)phenyl]methyl}-2-ethyl-1H-imidazole-5-carboxamideYield 28.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

HATU (0.113 g, 0.298 mmol) was added to a solution of {[4-chloro-2-fluoro-3-(1-naphthalenyloxy)phenyl]methyl}amine (0.060 g, 0.199 mmol) and 4-chloro-2-ethyl-1H-imidazole-5-carboxylic acid (0.035 g, 0.199 mmol) and diisopropylethylamine (0.052 mL, 0.298 mmol) in DMF (1 mL). The mixture was stirred at room temperature for 1 hr. The reaction mixture was extracted with ethyl acetate and water. The organic layer was washed with water and brine, dried over sodium sulfate and concentrated. The residue was purified by reverse phase HPLC (acetonitrile:water with 0.1% TFA) to give the title compound (0.026 g, 26%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.28-8.39 (m, 1H), 8.09-8.22 (m, 1H), 7.98 (dd, 1H), 7.57-7.69 (m, 3H), 7.51 (dd, 1H), 7.27-7.40 (m, 2H), 6.52 (d, 1H), 4.52 (d, 2H), 2.59 (q, 2H), 1.16 (t, 3H). ES MS: m/z 458 (M+1).

Workup

  1. extractionThe reaction mixture was extracted with ethyl acetate and water
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by reverse phase HPLC (acetonitrile:water with 0.1% TFA)

Sources & evidence

ORD record
ord-ffee3d2094e6454da351d4387ee1d44b
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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