Phosphorus oxychloride → HCID 68964147, compound

HRID 1821013Notes

Reaction equation

HRID 1821013 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:13]([NH:15][NH:16][C:17](=O)[C:18]2[CH:23]=[CH:22][C:21]([Br:24])=[CH:20][C:19]=2[CH3:25])=[O:14])[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11])#[N:2].P(Cl)(Cl)(Cl)=O>>[C:1]([C:3]1[CH:4]=[C:5]([C:13]2[O:14][C:17]([C:18]3[CH:23]=[CH:22][C:21]([Br:24])=[CH:20][C:19]=3[CH3:25])=[N:16][N:15]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:11])[CH3:12])#[N:2]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 68853800HCID 68853800, compound

Product 1

HCID 68964147HCID 68964147, compoundYield 86.8%

Procedure

In an oven-dried round bottom flask 145 mg (0.35 mmol) of N′-(3-cyano-4-isopropyloxyphenylcarbonyl)-4-bromo-2-methylbenzhydrazide (from EXAMPLE 87, Step A) was combined with 10 mL of anhydrous xylenes and 5 mL of phosphorus oxychloride and the heterogeneous reaction mixture was heated to reflux for 6 h. The resulting homogeneous mixture was cooled down to rt and combined with 200 mL of ice-water, neutralized to pH>10 and extracted with EtOAc (2×150 mL). The combined organic layers were dried with sodium sulfate and solvents were removed under reduced pressure. The crude compound was purified by flash chromatography using Biotage 40S (eluent: hexanes/EtOAc—4/1) to yield 121 mg of title compound: 1H NMR (500 MHZ, CDCl3) δ 1.50 (d, J=7.0, 6H), 2.78 (s, 3H), 4.80 (sep, J=7.0, 1H), 7.14 (d, J=9.0, 1H), 7.54 (dd, J=9.0, 2.0, 1H), 7.58 (d, J=2.0, 1H), 7.91 (d, J=8.5, 1H), 8.30 (d, J=2.0, 1H), 8.33 (dd, J=8.5, 2.0, 1H).

Workup

  1. temperaturethe heterogeneous reaction mixture was heated
  2. temperatureto reflux for 6 h
  3. extractionextracted with EtOAc (2×150 mL)
  4. dry with materialThe combined organic layers were dried with sodium sulfate and solvents
  5. customwere removed under reduced pressure
  6. customThe crude compound was purified by flash chromatography

Sources & evidence

ORD record
ord-f533bd729c0d4d3894dffa7ac61c3855
Source dataset
uspto-grants-2009_10
Patent number
US07605171B2

Reaction notes

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