Water → N-[4-chloro-3-(trifluoromethyl)phenyl]-7-{[2-(4,5-dihydro-1H-imidazol-2-yl)-pyridin-4-yl]oxy}-1,2,3,4-tetrahydronaphthalene-2-carboxamide

HRID 1640167Notes

Reaction equation

HRID 1640167 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([CH:11]2[CH2:20][CH2:19][C:18]3[C:13](=[CH:14][C:15]([OH:21])=[CH:16][CH:17]=3)[CH2:12]2)=[O:10])=[CH:4][C:3]=1[C:22]([F:25])([F:24])[F:23].Cl[C:27]1[CH:32]=[CH:31][N:30]=[C:29]([C:33]2[NH:34][CH2:35][CH2:36][N:37]=2)[CH:28]=1.C([O-])([O-])=O.[Cs+].[Cs+].O>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([CH:11]2[CH2:20][CH2:19][C:18]3[C:13](=[CH:14][C:15]([O:21][C:27]4[CH:32]=[CH:31][N:30]=[C:29]([C:33]5[NH:34][CH2:35][CH2:36][N:37]=5)[CH:28]=4)=[CH:16][CH:17]=3)[CH2:12]2)=[O:10])=[CH:4][C:3]=1[C:22]([F:23])([F:24])[F:25]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 58902317N-[4-chloro-3-(trifluoromethyl)phenyl]-7-hydroxy-1,2,3,4-tetrahydronaphthalene-2-carboxamideHCID 591349594-chloro-2-(4,5-dihydro-1H-imidazol-2-yl)pyridine

Product 1

HCID 23585215N-[4-chloro-3-(trifluoromethyl)phenyl]-7-{[2-(4,5-dihydro-1H-imidazol-2-yl)-pyridin-4-yl]oxy}-1,2,3,4-tetrahydronaphthalene-2-carboxamideYield 67.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-[4-chloro-3-(trifluoromethyl)phenyl]-7-hydroxy-1,2,3,4-tetrahydronaphthalene-2-carboxamide (64 mg, 0.17 mmol) and 4-chloro-2-(4,5-dihydro-1H-imidazol-2-yl)pyridine (35 mg, 0.19 mmol) in DMF (1.70 mL) was added Cs2CO3 (170 mg, 0.52 mmol). The mixture was irradiated in a microwave for 200 sec at 200° C. Water was added, and the mixture was extracted with EtOAc. The organic solution was washed with water (3×) and brine, dried over Na2SO4, filtered and evaporated. The residue was purified by column chromatography. The product was dissolved in MeOH, and 2.0M HCl in Et2O was added. The solvents were evaporated to give I-36 as a white solid (59 mg, 58%). 1H NMR (300 MHz, CD3OD): δ 8.62 (d, 1H), 8.17 (d, 1H), 7.82-7.78 (m, 1H), 7.63 (d, 1H), 7.53 (d, 1H), 7.25 (d, 1H), 7.21-7.18 (m, 1H), 6.96-6.91 (m, 2H), 4.11 (s, 4H), 3.14-2.82 (m, 5H), 2.24-2.16 (m, 1H), and 2.01-2.90 (m, 1H). LCMS: (FA) ES+ 516.2, ES− 513.2.

Workup

  1. customThe mixture was irradiated in a microwave for 200 sec at 200° C
  2. extractionthe mixture was extracted with EtOAc
  3. washThe organic solution was washed with water (3×) and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was purified by column chromatography
  8. dissolutionThe product was dissolved in MeOH
  9. addition2.0M HCl in Et2O was added
  10. customThe solvents were evaporated

Sources & evidence

ORD record
ord-9988032e1f5f40a898dd4443966accd6
Source dataset
uspto-grants-2012_02
Patent number
US08110687B2

Reaction notes

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