Hydrochloric Acid → 1-(2,4-difluorophenyl)-3-(3-fluoro-4-(2-(5-((2-methoxyethylamino)methyl)-1-methyl-1H-imidazol-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)urea

HRID 1026827Notes

Reaction equation

HRID 1026827 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10](=[O:48])[NH:11][C:12]1[CH:46]=[CH:45][C:15]([O:16][C:17]2[CH:22]=[CH:21][N:20]=[C:19]3[CH:23]=[C:24]([C:26]4[N:27]([CH3:44])[C:28]([CH2:31][N:32]([CH2:40][CH2:41][O:42][CH3:43])C(=O)OC(C)(C)C)=[CH:29][N:30]=4)[S:25][C:18]=23)=[C:14]([F:47])[CH:13]=1.Cl.O1CCOCC1.CCOC(C)=O>C(Cl)Cl.O.C([O-])(O)=O.[Na+]>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]([NH:11][C:12]1[CH:46]=[CH:45][C:15]([O:16][C:17]2[CH:22]=[CH:21][N:20]=[C:19]3[CH:23]=[C:24]([C:26]4[N:27]([CH3:44])[C:28]([CH2:31][NH:32][CH2:40][CH2:41][O:42][CH3:43])=[CH:29][N:30]=4)[S:25][C:18]=23)=[C:14]([F:47])[CH:13]=1)=[O:48]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 312751,4-DioxaneHCID 67049419tert-butyl(2-(7-(4-(3-(2,4-difluorophenyl)ureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1-methyl-1H-imidazol-5-yl)methyl(2-methoxyethyl)carbamate

Product 1

HCID 579194881-(2,4-difluorophenyl)-3-(3-fluoro-4-(2-(5-((2-methoxyethylamino)methyl)-1-methyl-1H-imidazol-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)ureaYield 61.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 350 (600 mg, 0.879 mmol) in DCM (15 ml) was added HCl in dioxane (2 ml, 7.17 eq, 8 mmol, 4M in dioxane) and the reaction mixture was stirred at RT for 3 hours. The mixture wad diluted with water and solid NaHCO3 was added. The reaction mixture was extracted with EtOAc then the organic phase was collected, dried over Na2SO4, filtered and concentrated. Trituration of the residue with EtOAc afforded the desired compound 351 as an off-white solid (314 mg, 61% yield). 1H NMR (d6-DMSO): 10.90 (s, 1H), 8.89 (s, 1H), 8.50 (d, J=5.48 Hz, 1H), 7.98 (m, 1H), 7.95 (s, 1H), 7.72 (m, 1H), 7.41 (m, 1H), 7.28-7.20 (m, 3H), 7.04 (m, 1H), 6.68 (d, J=5.28 Hz, 1H) 4.28 (s, 2H), 3.92 (s, 3H), 3.61 (m, 2H), 3.27 (s, 3H), 3.13 (m, 2H).

Workup

  1. additionwas added
  2. extractionThe reaction mixture was extracted with EtOAc
  3. customthe organic phase was collected
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-ae2c94cec6c441f29ecbd698cd030961
Source dataset
uspto-grants-2014_05
Patent number
US08729268B2

Reaction notes

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