Phosphorus oxychloride → HCID 58661542, compound

HRID 898700Notes

Reaction equation

HRID 898700 reaction equation
[F:1][C:2]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:3]=1[C:4]([N:6]([CH2:11][C:12]1[N:13]=[N:14][C:15]([CH:21]([NH:23][CH:24]=O)[CH3:22])=[CH:16][C:17]=1[CH2:18][CH2:19][CH3:20])[CH2:7][CH:8]([CH3:10])[CH3:9])=[O:5].O=P(Cl)(Cl)Cl>>[F:1][C:2]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:3]=1[C:4]([N:6]([CH2:7][CH:8]([CH3:10])[CH3:9])[CH2:11][C:12]1[C:17]([CH2:18][CH2:19][CH3:20])=[CH:16][C:15]2[N:14]([CH:24]=[N:23][C:21]=2[CH3:22])[N:13]=1)=[O:5]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 58661549HCID 58661549, compound

Product 1

HCID 58661542HCID 58661542, compound

Conditions

Temperature
100 °C

Procedure

A mixture of 2,5-difluoro-N-[6-(1-formylamino-ethyl)-4-propyl-pyridazin-3-ylmethyl]-N-isobutyl-benzamide (89 mg) and POCl3 (3 ml) is heated at 100° C. for 3 hours. The solvent is removed in vacuo and to the residue is added saturated NaHCO3 aqueous solution to neutralize the reaction mixture. EtOAc (10 ml) is added and the layers are separated. The aqueous layer is extracted with EtOAc (10 ml) and the combined extracts are washed with brine (10 ml), dried (Na2SO4) and evaporated. Flash column separation of the residue with 5% MeOH in CH2Cl2 gives the title compound as a light yellow oil. 1H NMR (CDCl3) (mixture of rotamers) 8.30 (s, 0.4H), 8.25 (s, 0.6H), 7.45 (s, 0.6H), 7.35 (s, 0.4H), 7.00-7.13 (m, 3H), 4.83 (s, 1.2H), 4.48 (s, 0.8H), 3.08 (d, 2H), 2.48 (s, 1.8H), 2.46 (s, 1.2H), 2.56 (t, 1.2H), 2.08-2.17 (m, 0.4H), 1.95-2.05 (m, 0.6H), 2.26 (t, 0.8H), 1.66-1.75 (m, 1.2H), 1.38-1.47 (m, 0.8H), 1.05 (t, 1.8H), 0.99 (d, 2.4H), 0.91 (t, 1.2H), 0.79 (d, 3.6H).

Workup

  1. customThe solvent is removed in vacuo and to the residue
  2. additionis added saturated NaHCO3 aqueous solution
  3. additionEtOAc (10 ml) is added
  4. customthe layers are separated
  5. extractionThe aqueous layer is extracted with EtOAc (10 ml)
  6. washthe combined extracts are washed with brine (10 ml)
  7. dry with materialdried (Na2SO4)
  8. customevaporated
  9. customFlash column separation of the residue with 5% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-d423b06f313b432999f58395ca898a29
Source dataset
uspto-grants-2008_04
Patent number
US07351826B2

Reaction notes

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