Phosphorus oxychloride → HCID 178501056, compound

HRID 2042340Notes

Reaction equation

HRID 2042340 reaction equation
[NH2:1][C:2]1[NH:7][C:6](=[O:8])[C:5]([CH2:9][NH:10][C:11]([C@H:13]2[CH2:18][CH2:17][C@H:16]([C:19]([O:21][CH3:22])=[O:20])[CH2:15][CH2:14]2)=O)=[N:4][N:3]=1.O=P(Cl)(Cl)Cl>ClCCCl>[NH2:1][C:2]1[NH:7][C:6](=[O:8])[C:5]2=[CH:9][N:10]=[C:11]([C@H:13]3[CH2:18][CH2:17][C@H:16]([C:19]([O:21][CH3:22])=[O:20])[CH2:15][CH2:14]3)[N:4]2[N:3]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178501156HCID 178501156, compound

Product 1

HCID 178501056HCID 178501056, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A solution of methyl trans-4-{[(3-amino-5-oxo-4,5-dihydro-1,2,4-triazin-6-yl)methyl]carbamoyl}cyclohexanecarboxylate (2.00 g, 0.00646 mol) in 1,2-dichloroethane (130 mL) was charged with POCl3 (4.2 mL, 0.045 mol) and heated to reflux for 3 h. The reaction mixture was concentrated in vacuo then partitioned between EtOAc and sat. NaHCO3 and separated. The aqueous was re-extracted with EtOAc (3×) and the combined organic fractions were dried over Na2SO4, filtered, and concentrated in vacuo resulting in 1.43 g, (76% yield) of the title compound as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.43 (q, J=11.79 Hz, 2H), 1.61 (q, J=12.55 Hz, 2H), 1.85-2.11 (m, 4H), 2.38 (t, J=11.87 Hz, 1H), 2.98 (t, J=11.75 Hz, 1H), 3.61 (s, 3H), 6.17 (br. s., 2 H), 7.49 (s, 1H) and 10.90 (br. s., 1H); MS (ES+): m/z 292.25 [MH+].

Workup

  1. temperatureheated
  2. temperatureto reflux for 3 h
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. customthen partitioned between EtOAc and sat. NaHCO3
  5. customseparated
  6. extractionThe aqueous was re-extracted with EtOAc (3×)
  7. dry with materialthe combined organic fractions were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-dadc8a145129466e841e3036c8a9f60d
Source dataset
uspto-grants-2013_11
Patent number
US08586546B2

Reaction notes

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