Hydrochloric Acid → 1-Cyclopropyl-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 1026824Notes

Reaction equation

HRID 1026824 reaction equation
[CH:1]1([NH:4][C:5](=[O:43])[NH:6][C:7]2[CH:41]=[CH:40][C:10]([O:11][C:12]3[CH:17]=[CH:16][N:15]=[C:14]4[CH:18]=[C:19]([C:21]5[N:22]([CH3:39])[C:23]([CH2:26][N:27]([CH2:35][CH2:36][O:37][CH3:38])C(=O)OC(C)(C)C)=[CH:24][N:25]=5)[S:20][C:13]=34)=[C:9]([F:42])[CH:8]=2)[CH2:3][CH2:2]1.Cl.O1CCOCC1>C(Cl)Cl.O.C([O-])(O)=O.[Na+]>[CH:1]1([NH:4][C:5]([NH:6][C:7]2[CH:41]=[CH:40][C:10]([O:11][C:12]3[CH:17]=[CH:16][N:15]=[C:14]4[CH:18]=[C:19]([C:21]5[N:22]([CH3:39])[C:23]([CH2:26][NH:27][CH2:35][CH2:36][O:37][CH3:38])=[CH:24][N:25]=5)[S:20][C:13]=34)=[C:9]([F:42])[CH:8]=2)=[O:43])[CH2:3][CH2:2]1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 58236627tert-Butyl (2-(7-(4-(3-cyclopropylureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1-methyl-1H-imidazol-5-yl)methyl(2-methoxyethyl)carbamate

Product 1

HCID 252699041-Cyclopropyl-3-(3-fluoro-4-(2-(5-((2-methoxyethylamino)methyl)-1-methyl-1H-imidazol-2-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)ureaYield 59.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of the 347 (426 mg, 0.698 mmol) in DCM (10 ml) was added HCl in dioxane (0.7 ml, 4.01 eq, 2.80 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 well with EtOAc then the organic phase was collected, dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography (eluent 25% MeOH in EtOAc to 50% MeOH in EtOAc) to afford the desired compound 348 as a yellow powder (211 mg, 59% yield). MS (m/z)=511.4 (M+H).

Workup

  1. additionwas added
  2. extractionThe reaction mixture was extracted well with EtOAc
  3. customthe organic phase was collected
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography (eluent 25% MeOH in EtOAc to 50% MeOH in EtOAc)

Sources & evidence

ORD record
ord-e9b4497087c94098b5f41c7383ebb97f
Source dataset
uspto-grants-2014_05
Patent number
US08729268B2

Reaction notes

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