Ammonium Acetate → 1-{4-Chloro-6-[1-(1-ethoxyethyl)-1H-pyrazol-4-yl]-3',5'-difluorobiphenyl-2-yl}ethanamine

HRID 510915Notes

Reaction equation

HRID 510915 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:9]=[N:10][N:11]([CH:13]([O:15][CH2:16][CH3:17])[CH3:14])[CH:12]=2)[C:5]([C:18]2[CH:23]=[C:22]([F:24])[CH:21]=[C:20]([F:25])[CH:19]=2)=[C:4]([C:26](=O)[CH3:27])[CH:3]=1.C([O-])(=O)C.[NH4+:33]>CO.C(#N)C>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:9]=[N:10][N:11]([CH:13]([O:15][CH2:16][CH3:17])[CH3:14])[CH:12]=2)[C:5]([C:18]2[CH:19]=[C:20]([F:25])[CH:21]=[C:22]([F:24])[CH:23]=2)=[C:4]([CH:26]([NH2:33])[CH3:27])[CH:3]=1

Participants

5

Reactant 2

HCID 517165Ammonium AcetateHCID 679691751-{4-Chloro-6-[1-(1-ethoxyethyl)-1H-pyrazol-4-yl]-3',5'-difluorobiphenyl-2-yl}ethanone

Product 1

HCID 679691831-{4-Chloro-6-[1-(1-ethoxyethyl)-1H-pyrazol-4-yl]-3',5'-difluorobiphenyl-2-yl}ethanamineYield 32%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Procedure

A solution of 1-{4-chloro-6-[1-(1-ethoxyethyl)-1H-pyrazol-4-yl]-3′,5′-difluorobiphenyl-2-yl}ethanone (190 mg, 0.47 mmol), ammonium acetate (360 mg, 4.7 mmol) in methanol (2 mL) and acetonitrile (2 mL) was heated at 65° C. for 3 hours. The reaction mixture was quenched with acetic acid (˜100 uL) and poured into sodium bicarbonate (50 mL). This mixture was extracted with dichloromethane (3×60 mL) and the combined organic layers were washed with brine, dried with sodium sulfate, filtered, and concentrated to a crude residue. Purification via preparative LCMS (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min) gave the desired product (60 mg, 32%). LCMS for C21H23ClF2N3O (M+H)+: m/z=406.1. Found: 406.1.

Workup

  1. customThe reaction mixture was quenched with acetic acid (˜100 uL)
  2. additionpoured into sodium bicarbonate (50 mL)
  3. extractionThis mixture was extracted with dichloromethane (3×60 mL)
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to a crude residue
  8. customPurification via preparative LCMS (XBridge C18 column
  9. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 60 mL/min)

Sources & evidence

ORD record
ord-76c30a31028b43ad84fc280b573892fb
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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