Phosgene → HCID 23630276、化合物

HRID 2066714ノート

反応式

HRID 2066714 の反応式
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]

参加物

9

反応物 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、化合物

生成物 1

HCID 23630276HCID 23630276、化合物

試薬・触媒・溶媒 3

HCID 1140Toluene溶媒HCID 6344Dichloromethane溶媒HCID 312751,4-Dioxane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-83679bcbe3214efb97e160b9d96c9de7
出典データセット
uspto-grants-2012_10
特許番号
US08293746B2

反応ノート

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