Nitrogen → [3-Chloro-4-(3-fluoro-benzyloxy)-phenyl]-(5-phenylsulfanylmethyl-pyrrolo[2,1-f][1,2,4]triazin-4-yl)-amine

HRID 1829915노트

반응식

HRID 1829915 반응식
Br[CH2:2][C:3]1[CH:4]=[CH:5][N:6]2[C:11]=1[C:10](Cl)=[N:9][C-:8]=[N:7]2.N#N.[C:15]1([SH:21])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(N(C(C)C)CC)(C)C.[Cl:31][C:32]1[CH:33]=[C:34]([NH2:47])[CH:35]=[CH:36][C:37]=1[O:38][CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[C:42]([F:46])[CH:41]=1>C(Cl)Cl.C(O)CCC.ClCCCl>[Cl:31][C:32]1[CH:33]=[C:34]([NH:47][C:10]2[C:11]3=[C:3]([CH2:2][S:21][C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=4)[CH:4]=[CH:5][N:6]3[N:7]=[CH:8][N:9]=2)[CH:35]=[CH:36][C:37]=1[O:38][CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[C:42]([F:46])[CH:41]=1

참가 물질

9

반응물 5

HCID 947NitrogenHCID 7969ThiophenolHCID 81531DiisopropylethylamineHCID 70592633-Chloro-4-(3-fluorobenzyloxy)anilineHCID 1317257935-bromomethyl-4-chloro-pyrrolo[2,1-f][1,2,4]triazine 1D

생성물 1

HCID 22055272[3-Chloro-4-(3-fluoro-benzyloxy)-phenyl]-(5-phenylsulfanylmethyl-pyrrolo[2,1-f][1,2,4]triazin-4-yl)-amine수율 50.9%

시약·촉매·용매 3

HCID 111,2-Dichloroethane용매HCID 2631-Butanol용매HCID 6344Dichloromethane용매

실험 절차

A solution of 5-bromomethyl-4-chloro-pyrrolo[2,1-f][1,2,4]triazine 1D (1.0 g, 4.1 mmol) in DCM (60 ml) was sparged with N2 for 0.5 hr and then placed in a −20° C. bath. Thiophenol (0.42 ml, 4.1 mmol) and diisopropylethylamine (0.713 ml, 4.1 mmol) were added and the reaction was kept at −20° C. for 3 hr. After warming to rt, the reaction mixture was washed with water, dried (Na2SO4), and the solvent was removed. 1,2-Dichloroethane (20 ml), n-butanol (20 ml) and 3-chloro-4-(3-fluoro-benzyloxy)-phenylamine 3A (900 mg, 3.6 mmol) were added to the residue and the mixture was heated at 85° C. for 2.5 hr. The solvents were removed and the residue was taken up in DCM, washed with sat. aq. NaHCO3 solution and dried (Na2SO4). Removal of the solvent followed by chromatography on silica gel using DCM containing 0 to 5% MeOH as eluent afforded 7A (0.90 g, 50%) as a foam. LC/MS M++1=491; 1H-NMR (CDCl3):δ 4.51 (s, 2H), 5.15 (s, 2H), 6.52 (d, 1H, J=3 Hz), 6.93 (d, 1H, J=9 Hz), 7.02–7.49 (m, 11H), 7.80 (m, 1H, J=3 Hz), 8.18 (s, 1H), 8.74 (s, 1H).

후처리

  1. customplaced in a −20° C.
  2. washthe reaction mixture was washed with water
  3. dry with materialdried (Na2SO4)
  4. customthe solvent was removed
  5. temperaturethe mixture was heated at 85° C. for 2.5 hr
  6. customThe solvents were removed
  7. washwashed with sat. aq. NaHCO3 solution
  8. dry with materialdried (Na2SO4)
  9. customRemoval of the solvent

출처 및 근거

ORD 기록
ord-cb323c00bada47f1b16810c889d0154e
출처 데이터셋
uspto-grants-2006_06
특허 번호
US07064203B2

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