Phosgene → 1-(5-tert-butyl-2-methoxy-phenyl)-3-[4-(2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)-naphthalen-1-yl)-urea

HRID 2417007노트

반응식

HRID 2417007 반응식
[C:1]([C:5]1[CH:6]=[C:7]([NH2:13])[C:8](=[CH:11][CH:12]=1)[O:9][CH3:10])([CH3:4])([CH3:3])[CH3:2].C(Cl)(Cl)=O.[N-:18]=[C:19]=[O:20].Cl.N[C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]([C:33]2[CH:43]=[N:42][C:36]3[O:37][CH2:38][C:39](=[O:41])[NH:40][C:35]=3[CH:34]=2)=[CH:25][CH:24]=1.C(N(C(C)C)CC)(C)C>ClCCl.C([O-])(O)=O.[Na+].C1COCC1.CCOC(C)=O>[C:1]([C:5]1[CH:12]=[CH:11][C:8]([O:9][CH3:10])=[C:7]([NH:13][C:19]([NH:18][C:23]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[C:26]([C:33]3[CH:43]=[N:42][C:36]4[O:37][CH2:38][C:39](=[O:41])[NH:40][C:35]=4[CH:34]=3)=[CH:25][CH:24]=2)=[O:20])[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

참가 물질

10

반응물 5

HCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 105034IsocyanateHCID 41763185-tert-Butyl-o-anisidineHCID 226314107-(4-amino-naphthalen-1-yl)-1H-pyrido[2,3-b][1,4]oxazin-2-one hydrochloride

생성물 1

HCID 102285491-(5-tert-butyl-2-methoxy-phenyl)-3-[4-(2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-yl)-naphthalen-1-yl)-urea

시약·촉매·용매 4

HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매HCID 516892Sodium Bicarbonate용매

실험 절차

To 4-tert-butyl-o-anisidine (0.035 g, 0.198 mmol) in 2 mL dichloromethane and 2 mL saturated aqueous NaHCO3 at 0° C., phosgene (˜2 M in toluene, 0.21 mL, 0.40 mmol) was added via syringe to the organic layer in one portion, while not stirring. The resulting mixture was stirred vigorously for 10 min, then the organic layer was separated and dried (MgSO4), filtered and concentrated in vacuo. To the resulting isocyanate solution was added a solution of 7-(4-amino-naphthalen-1-yl)-1H-pyrido[2,3-b][1,4]oxazin-2-one hydrochloride (Example 7) (72 mg, 0.220 mmol) and diisopropyl ethylamine (42 uL, 0.242 mmol) in 2 mL anhydrous THF. This mixture was stirred overnight, then diluted with EtOAc, washed with water and brine, dried (MgSO4), filtered and the solvents removed in vacuo. The residue was purified by preparative HPLC to afford 12 mg of the title compound, m.p.>200° C.

후처리

  1. stirringThe resulting mixture was stirred vigorously for 10 min
  2. customthe organic layer was separated
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. stirringThis mixture was stirred overnight
  7. washwashed with water and brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. customthe solvents removed in vacuo
  11. customThe residue was purified by preparative HPLC

출처 및 근거

ORD 기록
ord-549cc07b5a20466a97ef9dd9ebb4aa1e
출처 데이터셋
uspto-grants-2004_11
특허 번호
US06825184B2

반응 노트

불러오는 중…