Diisopropylethylamine → HCID 178437659, compound

HRID 1875140Notes

Reaction equation

HRID 1875140 reaction equation
[NH2:1][CH2:2][C:3]1[C:4]([F:23])=[C:5]([O:10][C:11]2[CH:12]=[C:13]([CH:16]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:18]=2)[C:14]#[N:15])[C:6]([Cl:9])=[CH:7][CH:8]=1.[Cl:24][C:25]1[N:26]=[C:27]([CH2:33][CH3:34])[NH:28][C:29]=1[C:30](O)=[O:31].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C>[Cl:24][C:25]1[N:26]=[C:27]([CH2:33][CH3:34])[NH:28][C:29]=1[C:30]([NH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([Cl:9])=[C:5]([O:10][C:11]2[CH:18]=[C:17]([C:19]([F:22])([F:20])[F:21])[CH:16]=[C:13]([C:14]#[N:15])[CH:12]=2)[C:4]=1[F:23])=[O:31]

Participants

7

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 684835233-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-(trifluoromethyl)benzonitrileHCID 178437661HCID 178437661, compound

Product 1

HCID 178437659HCID 178437659, compoundYield 47%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-(trifluoromethyl)benzonitrile (197 mg, 0.573 mmol), 4-chloro-2-ethyl-1H-imidazole-5-carboxylic acid (100 mg, 0.573 mmol) and HATU (218 mg, 0.573 mmol) in DMF (4.0 ml) was added diisopropylethyl amine (0.200 ml, 1.146 mmol) and the mixture was stirred for 1 hr at rt. The reaction mixture was diluted with ethyl acetate and washed with water. The solvent was removed and the crude material was purified via silica gel chromatography to give 4-chloro-N-[(4-chloro-3-{[3-cyano-5-(trifluoromethyl)phenyl]oxy}-2-fluorophenyl)methyl]-2-ethyl-1H-imidazole-5-carboxamide (135 mg, 0.269 mmol, 47% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.11 (s, 2H), 7.80 (s, 1H), 7.74 (s, 1H), 7.50 (dd, 1H), 7.36 (t, 1H), 4.52 (d, 2H), 2.58 (q, 2H), 1.16 (t, 3H). LC-MS (ES+) m/z 501.10, [M+H].

Workup

  1. washwashed with water
  2. customThe solvent was removed
  3. customthe crude material was purified via silica gel chromatography

Sources & evidence

ORD record
ord-05503821c82d43e286addd84529c6833
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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