p-Toluenesulfonic acid → HCID 66740907, compound

HRID 1627317Notes

Reaction equation

HRID 1627317 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]([C:14]2[N:18]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[C:17]([CH:26]=O)=[N:16][CH:15]=2)([CH3:13])[CH3:12])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[Cl:28][C:29]1[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[C:30]=1[NH2:31].CC1C=CC(S(O)(=O)=O)=CC=1.[BH4-].[Na+]>C1COCC1>[Cl:28][C:29]1[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[C:30]=1[NH:31][CH2:26][C:17]1[N:18]([C:19]2[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=2)[C:14]([C:11]([C:5]2[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=2)([CH3:12])[CH3:13])=[CH:15][N:16]=1

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 27342052-Chloro-6-fluoroanilineHCID 4311764Sodium borohydrideHCID 86662236HCID 86662236, compound

Product 1

HCID 66740907HCID 66740907, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 5-(2-(3,4-dimethoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole-2-carbaldehyde (280 mg, 0.76 mmol), 2-chloro-6-fluoroaniline (332 mg, 2.28 mmol), TsOH (72 mg, 0.38 mmol) in THF (8 mL) was heated at reflux for 15 h over molecular sieves (4A). The solution was cooled to 0° C., and NaBH4 (57 mg, 1.5 2 mmol) was added in several portions. The resulting mixture was stirring for 1 h, and filtered through Celite™ to remove molecular sieves. The filtrate was quenched with H2O (5 mL), 2N NaOH (5 mL) and extracted with DCM (2×10 mL). The organic layers were dried over MgSO4 and concentrated to give a residue, which was purified by flash chromatography to provide the title compound as a white solid (157 mg, 0.315 mmol, 42%). 1H NMR (400 MHz, CDCl3) δ1.49 (s, 6H), 3.72 (s, 3H), 3.85 (s, 3H), 4.13 (d, 2H), 4.65 (br, 1H), 6.45 (dd, 1H), 6.48 (m, 2H), 6.51 (d, 1H), 6.60 (m, 1H), 6.64 (d, 1H), 6.76 (dd, 1H), 6.80 (t, 2H), 7.00 (dt, 1H), 7.13 (s, 1H). MS (EI) m/z 498 [M+H]+.

Workup

  1. filtrationfiltered through Celite™
  2. customto remove molecular sieves
  3. customThe filtrate was quenched with H2O (5 mL), 2N NaOH (5 mL)
  4. extractionextracted with DCM (2×10 mL)
  5. dry with materialThe organic layers were dried over MgSO4
  6. concentrationconcentrated
  7. customto give a residue, which
  8. customwas purified by flash chromatography

Sources & evidence

ORD record
ord-dd3cc0b174a3447e839e00be914aa48c
Source dataset
uspto-grants-2014_07
Patent number
US08785488B2

Reaction notes

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