Phosgene → HCID 23630276, compound

HRID 409684Notes

Reaction equation

HRID 409684 reaction equation
C(Cl)(Cl)=O.ClC1C(C(F)(F)F)=C(Cl)C(OC)=CC=1N.[Cl:20][C:21]1[C:26]([C:27]([F:30])([F:29])[F:28])=[C:25]([Cl:31])[C:24]([O:32][CH3:33])=[CH:23][C:22]=1[N:34]=[C:35]=[O:36].[CH2:37]([N:39]1[CH2:44][CH2:43][N:42]([C:45]2[CH:50]=[CH:49][C:48]([NH:51][C:52]3[CH:57]=[C:56]([NH:58][CH3:59])[N:55]=[CH:54][N:53]=3)=[CH:47][CH:46]=2)[CH2:41][CH2:40]1)[CH3:38].C([O-])(O)=O.[Na+]>O1CCOCC1.C1(C)C=CC=CC=1.C(Cl)Cl>[Cl:20][C:21]1[C:26]([C:27]([F:28])([F:30])[F:29])=[C:25]([Cl:31])[C:24]([O:32][CH3:33])=[CH:23][C:22]=1[NH:34][C:35](=[O:36])[N:58]([C:56]1[CH:57]=[C:52]([NH:51][C:48]2[CH:47]=[CH:46][C:45]([N:42]3[CH2:41][CH2:40][N:39]([CH2:37][CH3:38])[CH2:44][CH2:43]3)=[CH:50][CH:49]=2)[N:53]=[CH:54][N:55]=1)[CH3:59]

Participants

9

Reactant 5

HCID 6371PhosgeneHCID 516892Sodium BicarbonateHCID 56594616N4-(4-(4-Ethyl-1-piperazinyl)phenyl)-N6-methyl-4,6-pyrimidinediamineHCID 866254602,4-Dichloro-5-methoxy-3-trifluoromethylanilineHCID 86625461HCID 86625461, compound

Product 1

HCID 23630276HCID 23630276, compound

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

Phosgene (20% in toluene, 0.54 mL, 1.0 mmol, 2.0 equiv) is added to a solution of 2,4-dichloro-5-methoxy-3-trifluoromethylaniline (156 mg, 0.60 mmol, 1.2 equiv) in dioxane (2 mL), under a nitrogen atmosphere. The mixture is heated to reflux, stirred for 75 min, allowed to cool to RT, and concentrated in vacuo. The resulting solid 2,4-dichloro-5-methoxy-3-trifluoromethyl-phenylisocyanate is added portion-wise to a boiling solution of N-[4-(4-ethyl-piperazin-1-yl)-phenyl]-N′-methyl-pyrimidine-4,6-diamine (156 mg, 0.50 mmol; preparation see Step 25.5) in 6 ml of toluene under a nitrogen atmosphere. The reaction mixture is stirred at 110° C. for 3.3 h, allowed to cool to RT, and diluted with DCM and a saturated aqueous solution of NaHCO3. The aqueous layer is separated off and extracted twice with DCM. The organic phase is washed with brine, dried (Na2SO4), filtered and concentrated. Trituration of the resulting solid with 2 portions of MeOH yields the title compound: ESI-MS: 598/600 [MH]+; tR=5.1 min (purity: 97%, system 1).

Workup

  1. temperatureThe mixture is heated
  2. temperatureto reflux
  3. concentrationconcentrated in vacuo
  4. stirringThe reaction mixture is stirred at 110° C. for 3.3 h
  5. temperatureto cool to RT
  6. customThe aqueous layer is separated off
  7. extractionextracted twice with DCM
  8. washThe organic phase is washed with brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-32c7ea36d3134a00b917e07edb6355b5
Source dataset
uspto-grants-2014_06
Patent number
US08759517B2

Reaction notes

Loading…