Phosgene → HCID 58659451, compound

HRID 1993572Notes

Reaction equation

HRID 1993572 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([O:8][C:9]2[CH:15]=[CH:14][C:12]([NH2:13])=[CH:11][CH:10]=2)[CH:3]=1.CCN(CC)CC.[C:23](Cl)(Cl)=[O:24].[CH2:27]([N:29]1[CH2:34][CH2:33][N:32]([CH2:35][C:36]2[CH:37]=[C:38]([NH2:46])[CH:39]=[C:40]([C:42]([F:45])([F:44])[F:43])[CH:41]=2)[CH2:31][CH2:30]1)[CH3:28]>C(Cl)Cl.C1(C)C=CC=CC=1.C1COCC1.O.CCOC(C)=O>[Cl:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([O:8][C:9]2[CH:15]=[CH:14][C:12]([NH:13][C:23]([NH:46][C:38]3[CH:39]=[C:40]([C:42]([F:43])([F:44])[F:45])[CH:41]=[C:36]([CH2:35][N:32]4[CH2:31][CH2:30][N:29]([CH2:27][CH3:28])[CH2:34][CH2:33]4)[CH:37]=3)=[O:24])=[CH:11][CH:10]=2)[CH:3]=1

Participants

10

Reactant 4

HCID 6371PhosgeneHCID 8471Triethylamine2×HCID 226137114-((6-Chloropyrimidin-4-yl)oxy)anilineHCID 58659410HCID 58659410, compound

Product 1

HCID 58659451HCID 58659451, compound

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To an ice-cold solution of 4-(6-chloro-pyrimidin-4-yl-oxy)-aniline (Stage 21.1; 0.926 g, 4.18 mmol) and NEt3 (0.64 ml, 4.6 mmol) in CH2Cl2 (30 ml) under N2-atmosphere, phosgene (2.32 ml of a 20% solution in toluene, 4.39 mmol) in CH2Cl2 (10 ml) is added dropwise. The resulting suspension is stirred for 1 h, then filtered under exclusion of moisture and the filtrate concentrated in vacuo. THF (20 ml) and NEt3 (0.64 ml, 4.6 mmol) is then added to the residue. After cooling in an ice bath, 3-(4-ethyl-piperazin-1-ylmethyl)-5-trifluoromethyl-phenylamine (1.00 g, 3.48 mmol) dissolved in THF (20 ml) is added dropwise and the reaction mixture stirred for 30 min at 0° C. and 2 h at rt. Then it is diluted with water and AcOEt, the aqueous layer separated off and extracted twice with AcOEt. The organic phases are washed with water and brine, dried (Na2SO4) and concentrated. Column chromatography (SiO2; AcOEt/EtOH/Et3N 90:10:2→80:20:2) and crystallization from ether affords the title compound: m.p.: 168-169° C.; MS: [M+1]+=535; 1H-NMR (CD3OD): 8.54 (s, 1H), 7.82 (s, 1H), 7.60 (s, 1H), 7.54 (d, 2H), 7.30 (s, 1H), 7.14 (d, 2H), 7.09 (s, 1H), 3.60 (s, 2H), 2.57 (m, 8H), 2.47 (q, 2H), 1.12 (t, 3H).

Workup

  1. filtrationfiltered under exclusion of moisture
  2. concentrationthe filtrate concentrated in vacuo
  3. temperatureAfter cooling in an ice bath
  4. additionis added dropwise
  5. stirringthe reaction mixture stirred for 30 min at 0° C. and 2 h at rt
  6. customthe aqueous layer separated off
  7. extractionextracted twice with AcOEt
  8. washThe organic phases are washed with water and brine
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated
  11. customColumn chromatography (SiO2; AcOEt/EtOH/Et3N 90:10:2→80:20:2) and crystallization from ether

Sources & evidence

ORD record
ord-24c471ffdc2749d2bb268521e86c8860
Source dataset
uspto-grants-2010_01
Patent number
US07652022B2

Reaction notes

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