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

HRID 1829915Notes

Reaction equation

HRID 1829915 reaction equation
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

Participants

9

Reactant 5

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 2631-ButanolSolventHCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-cb323c00bada47f1b16810c889d0154e
Source dataset
uspto-grants-2006_06
Patent number
US07064203B2

Reaction notes

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