Phosgene → HCID 23630278, 화합물

HRID 2066684

반응식

HRID 2066684 반응식
C(Cl)(Cl)=O.[Cl:5][C:6]1[C:12]([O:13][CH3:14])=[CH:11][C:10]([O:15][CH3:16])=[C:9]([Cl:17])[C:7]=1[NH2:8].[N-:18]=[C:19]=[O:20].[N:21]1([CH2:27][CH2:28][O:29][C:30]2[CH:35]=[CH:34][C:33]([NH:36][C:37]3[CH:42]=[C:41](N)[N:40]=[CH:39][N:38]=3)=[CH:32][CH:31]=2)[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1.C([O-])(O)=O.[Na+]>O1CCOCC1.CN1C(=O)CCC1.C(Cl)Cl>[Cl:5][C:6]1[C:12]([O:13][CH3:14])=[CH:11][C:10]([O:15][CH3:16])=[C:9]([Cl:17])[C:7]=1[NH:8][C:19]([NH:18][C:41]1[CH:42]=[C:37]([NH:36][C:33]2[CH:34]=[CH:35][C:30]([O:29][CH2:28][CH2:27][N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=[CH:31][CH:32]=2)[N:38]=[CH:39][N:40]=1)=[O:20]

참가 물질

9

반응물 5

HCID 6371PhosgeneHCID 105034IsocyanateHCID 516892Sodium BicarbonateHCID 594862532,6-Dichloro-3,5-dimethoxyanilineHCID 59864576N-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-pyrimidine-4,6-diamine

생성물 1

HCID 23630278HCID 23630278, 화합물

시약·촉매·용매 3

HCID 6344Dichloromethane용매HCID 13387N-methyl-2-pyrrolidone용매HCID 312751,4-Dioxane용매

실험 절차

Phosgene (20% in toluene, 0.8 mL, 1.58 mmol, 2.4 equiv) is added to a solution of 2,6-dichloro-3,5-dimethoxyaniline (175 mg, 0.79 mmol, 1.2 equiv) in dioxane (2.5 mL), under an argon atmosphere. The mixture is heated to reflux, stirred for 1 h, allowed to cool to RT, and concentrated in vacuo. The resulting isocyanate is added to a solution of N-[4-(2-morpholin-4-yl-ethoxy)-phenyl]-pyrimidine-4,6-diamine (208.5 mg, 0.66 mmol) in NMP (2 mL), at 75° C. and under an argon atmosphere. The reaction mixture is stirred at 75° C. for 2 h, allowed to cool to RT, and is then diluted with DCM and a saturated aqueous solution of NaHCO3. The aqueous layer is separated and extracted with DCM. The organic phase is washed with brine, dried (Na2SO4), filtered and concentrated. Purification of the crude product by silica gel column chromatography (DCM/MeOH+1% NH3aq, 96:4), followed by trituration of the resulting material in MeOH, affords the title compound as a white solid: ESI-MS: 562.9/564.9 [MH]+; tR=2.99 min (purity: 100%, system 1); TLC: Rf=0.36 (DCM/MeOH+1% NH3aq, 93:7).

후처리

  1. temperatureThe mixture is heated
  2. temperatureto reflux
  3. concentrationconcentrated in vacuo
  4. stirringThe reaction mixture is stirred at 75° C. for 2 h
  5. temperatureto cool to RT
  6. customThe aqueous layer is separated
  7. extractionextracted with DCM
  8. washThe organic phase is washed with brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customPurification of the crude product by silica gel column chromatography (DCM/MeOH+1% NH3aq, 96:4)

출처 및 근거

ORD 기록
ord-55e3d22c6fc14225b5fe84a81bbb8568
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08293746B2

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