Phosgene → HCID 23630277, compound

HRID 2066719Notes

Reaction equation

HRID 2066719 reaction equation
C(Cl)(Cl)=O.COC1C=C(C(F)(F)F)C=C(C=1)N.[CH3:18][O:19][C:20]1[CH:21]=[C:22]([C:29]([F:32])([F:31])[F:30])[CH:23]=[C:24]([N:26]=[C:27]=[O:28])[CH:25]=1.[CH2:33]([N:35]1[CH2:40][CH2:39][N:38]([C:41]2[CH:46]=[CH:45][C:44]([NH:47][C:48]3[CH:53]=[C:52]([NH:54][CH3:55])[N:51]=[CH:50][N:49]=3)=[CH:43][CH:42]=2)[CH2:37][CH2:36]1)[CH3:34].C([O-])(O)=O.[Na+]>O1CCOCC1.C1(C)C=CC=CC=1.C(Cl)Cl>[CH3:18][O:19][C:20]1[CH:21]=[C:22]([C:29]([F:30])([F:31])[F:32])[CH:23]=[C:24]([NH:26][C:27](=[O:28])[N:54]([C:52]2[CH:53]=[C:48]([NH:47][C:44]3[CH:43]=[CH:42][C:41]([N:38]4[CH2:37][CH2:36][N:35]([CH2:33][CH3:34])[CH2:40][CH2:39]4)=[CH:46][CH:45]=3)[N:49]=[CH:50][N:51]=2)[CH3:55])[CH:25]=1

Participants

9

Reactant 5

HCID 6371PhosgeneHCID 516892Sodium BicarbonateHCID 6056715-(Trifluoromethyl)-m-anisidineHCID 56594616N4-(4-(4-Ethyl-1-piperazinyl)phenyl)-N6-methyl-4,6-pyrimidinediamineHCID 58086654HCID 58086654, compound

Product 1

HCID 23630277HCID 23630277, compound

Reagents, catalysts & solvents 3

HCID 1140TolueneSolvent2×HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

Phosgene (20% in toluene, 1.62 mL, 3.0 mmol, 2.0 equiv) is added to a solution of 5-methoxy-3-trifluoromethylaniline (344 mg, 1.8 mmol, 1.2 equiv) in dioxane (6 mL) under a nitrogen atmosphere. The mixture is heated to reflux, stirred for 80 min, allowed to cool to RT, and concentrated in vacuo. During 45 min, a concentrated solution of the resulting oily 5-methoxy-3-trifluoromethyl-phenylisocyanate in toluene is added portion-wise to a boiling solution of N-[4-(4-ethyl-piperazin-1-yl)-phenyl]-N′-methyl-pyrimidine-4,6-diamine (468 mg, 1.50 mmol; Step 242.1) in 18 ml of toluene under a nitrogen atmosphere. The reaction mixture is stirred at 110° C. for 4 h, allowed to cool to RT, and diluted with DCM and a saturated aqueous solution of NaHCO3. The aqueous layer is separated and extracted twice with DCM. The organic phases are washed with brine, dried (Na2SO4), filtered and concentrated. Column chromatography (DCM/MeOH, 49:1→24:1) provides the title compound: API-MS: 530/532 [MH]+; TLC: Rf=0.4 (DCM/MeOH, 9:1); tR=4.3 min (purity: 100%, system 1).

Workup

  1. temperatureThe mixture is heated
  2. temperatureto reflux
  3. concentrationconcentrated in vacuo
  4. waitDuring 45 min
  5. stirringThe reaction mixture is stirred at 110° C. for 4 h
  6. temperatureto cool to RT
  7. customThe aqueous layer is separated
  8. extractionextracted twice with DCM
  9. washThe organic phases are washed with brine
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-6b483d577d5a4cf5a7c294dc8418387c
Source dataset
uspto-grants-2012_10
Patent number
US08293746B2

Reaction notes

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