Ammonium Hydroxide → (3-(4-(1H-Pyrazol-1-yl)benzyl)-2,4-dichloro-8-methylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone

HRID 926464Notes

Reaction equation

HRID 926464 reaction equation
[CH3:1][N:2]1[C:6]([C:7]([C:9]2[CH:14]=[CH:13][C:12]([N+:15]([O-])=O)=[C:11]([CH3:18])[CH:10]=2)=[O:8])=[CH:5][N:4]=[CH:3]1.[N:19]1([C:24]2[CH:43]=[CH:42][C:27]([CH2:28][C:29]3[C:30]([Cl:41])=NC4C([C:38]=3[Cl:39])=CC(Br)=CC=4)=[CH:26][CH:25]=2)[CH:23]=[CH:22][CH:21]=[N:20]1.O=P(Cl)(Cl)Cl.[NH4+].[OH-]>>[N:19]1([C:24]2[CH:25]=[CH:26][C:27]([CH2:28][C:29]3[C:30]([Cl:41])=[N:15][C:12]4[C:13]([C:38]=3[Cl:39])=[CH:14][C:9]([C:7]([C:6]3[N:2]([CH3:1])[CH:3]=[N:4][CH:5]=3)=[O:8])=[CH:10][C:11]=4[CH3:18])=[CH:42][CH:43]=2)[CH:23]=[CH:22][CH:21]=[N:20]1

Participants

5

Reactant 4

HCID 14923Ammonium HydroxideHCID 24813Phosphorus oxychlorideHCID 867155943-(4-(1H-pyrazol-1-yl)benzyl)-6-bromo-2,4-dichloroquinoline2×HCID 86715615(1-Methyl-1H-imidazol-5-yl)(3-methyl-4-nitrophenyl)methanone2×

Product 1

HCID 118005956(3-(4-(1H-Pyrazol-1-yl)benzyl)-2,4-dichloro-8-methylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone

Conditions

Temperature
105 °C

Procedure

A heterogeneous mixture of (4-amino-3-methylphenyl)(1-methyl-1H-imidazol-5-yl)methanone (1.0 g, 4.6 mmol, Intermediate 14: step c), 2-(4-(1H-pyrazol-1-yl)benzyl)malonic acid (1.3 g, 4.6 mmol, Intermediate 3: step b) and POCl3 (4.3 mL) was heated at 105° C. for 18 hours then cooled to room temperature. The mixture was poured into ice water and treated with aqueous NH4OH solution (kept adding ice during addition) to a basic pH 8-9. The aqueous layer was extracted with DCM, washed with a saturated aqueous solution of NaCl, dried (MgSO4) and concentrated. The crude product was purified by flash column chromatography (silica gel, 0-100% EtOAc/DCM) to provide the title compound.

Workup

  1. temperaturethen cooled to room temperature
  2. extractionThe aqueous layer was extracted with DCM
  3. washwashed with a saturated aqueous solution of NaCl
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe crude product was purified by flash column chromatography (silica gel, 0-100% EtOAc/DCM)

Sources & evidence

ORD record
ord-1590cbbd4d3940b4b91bc32cd5840159
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

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