Phosphorus oxychloride → 3-(1-chlorophthalazin-6-yl)-N-cyclopropyl-4-methylbenzamide

HRID 2357538Notes

Reaction equation

HRID 2357538 reaction equation
O[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]3[CH:13]=[C:14]([CH:18]=[CH:19][C:20]=3[CH3:21])[C:15]([OH:17])=O)=[CH:9][CH:10]=2)[CH:5]=[N:4][N:3]=1.P(Cl)(Cl)([Cl:24])=O.C([N:30]([CH:33]([CH3:35])[CH3:34])CC)(C)C.C1(N)CC1>>[Cl:24][C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]3[CH:13]=[C:14]([CH:18]=[CH:19][C:20]=3[CH3:21])[C:15]([NH:30][CH:33]3[CH2:35][CH2:34]3)=[O:17])=[CH:9][CH:10]=2)[CH:5]=[N:4][N:3]=1

Participants

5

Reactant 4

HCID 24813Phosphorus oxychlorideHCID 69828CyclopropylamineHCID 81531DiisopropylethylamineHCID 178425877HCID 178425877, compound

Product 1

HCID 118483123-(1-chlorophthalazin-6-yl)-N-cyclopropyl-4-methylbenzamideYield 50.2%

Conditions

Temperature
80 °C

Procedure

A suspension of 3-(1-hydroxyphthalazin-6-yl)-4-methylbenzoic acid (1.0 g, 3.6 mmol) in phosphorous oxychloride (4.9 mL, 54 mmol) was heated at 80° C. for 1 h. The solution was cooled and concentrated. Toluene (10 mL) was added and removed in vacuo. The brown syrup was resuspended in DCM (20 mL) and cooled to 0° C. Diisopropylethylamine (3.1 mL, 18 mmol) followed by cyclopropylamine (3.0 mL, 43 mmol) was added and the mixture was allowed to warm up to RT and stirred for 1 hour. The mixture was concentrated and the crude product was purified by silica gel chromatography (50-100% EtOAc in hexanes) to give 610 mg of 3-(1-chlorophthalazin-6-yl)-N-cyclopropyl-4-methylbenzamide as an off-white solid. MS (ES+)=338.1 (M+H)

Workup

  1. temperatureThe solution was cooled
  2. concentrationconcentrated
  3. additionToluene (10 mL) was added
  4. customremoved in vacuo
  5. temperaturecooled to 0° C
  6. additionwas added
  7. temperatureto warm up to RT
  8. concentrationThe mixture was concentrated
  9. customthe crude product was purified by silica gel chromatography (50-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-fd7c1be592e749c39cdd81026342ad77
Source dataset
uspto-grants-2010_07
Patent number
US07759337B2

Reaction notes

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