Hydrochloric Acid → (S)-2-amino-N-((2-(7-(4-(3-(2,4-difluorophenyl)ureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1-methyl-1H-imidazol-5-yl)methyl)-N-(2-methoxyethyl)-3-methylbutanamide

HRID 409982Notes

Reaction equation

HRID 409982 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:55])[NH:11][C:12]1[CH:53]=[CH:52][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]([CH3:51])[C:28]([CH2:31][N:32]([CH2:47][CH2:48][O:49][CH3:50])[C:33](=[O:46])[C@@H:34]([NH:38]C(=O)OC(C)(C)C)[CH:35]([CH3:37])[CH3:36])=[CH:29][N:30]=4)[S:25][C:18]=23)=[C:14]([F:54])[CH:13]=1.Cl.O1CCOCC1>C(Cl)Cl.O.C([O-])(O)=O.[Na+]>[NH2:38][C@@H:34]([CH:35]([CH3:37])[CH3:36])[C:33]([N:32]([CH2:31][C:28]1[N:27]([CH3:51])[C:26]([C:24]2[S:25][C:18]3[C:19](=[N:20][CH:21]=[CH:22][C:17]=3[O:16][C:15]3[CH:52]=[CH:53][C:12]([NH:11][C:10]([NH:9][C:3]4[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=4[F:1])=[O:55])=[CH:13][C:14]=3[F:54])[CH:23]=2)=[N:30][CH:29]=1)[CH2:47][CH2:48][O:49][CH3:50])=[O:46]

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 67048306(S)-tert-butyl 1-(((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)amino)-3-methyl-1-oxobutan-2-ylcarbamate

Product 1

HCID 67048202(S)-2-amino-N-((2-(7-(4-(3-(2,4-difluorophenyl)ureido)-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-1-methyl-1H-imidazol-5-yl)methyl)-N-(2-methoxyethyl)-3-methylbutanamideYield 89%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a suspension of the compound 352 (200 mg, 0.256 mmol) in DCM (10 ml) was added HCl in dioxane (0.7 ml, 10.95 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 with EtOAc then the organic phase was collected, dried over Na2SO4, filtered and concentrated. Purification of the residue by column chromatography (eluent 30% MeOH in EtOAc) afforded the desired compound 353 as pale yellow powder (155 mg, 89% yield). 1H NMR (d6-DMSO) 9.36 (s, 1H), 8.60 (s, 1H), 8.49 (m, 1H), 8.01 (m, 1H), 7.87 (s, 1H), 7.71 (m, 1H), 7.41 (t, J=8.99 Hz, 1H), 7.31 (m, 1H), 7.20 (m, 1H), 7.02 (m, 1H), 6.98 (s, 1H), 6.65 (d, J=5.09 Hz, 1H), 4.83 (d, J=15.65 Hz, 1H), 4.48 (d, J=15.65 Hz, 1H), 3.81 (s, 1H), 3.80 (s, 2H), 3.40 (m, 1H), 3.39-3.295 (m, 6H), 1.71 (m, 2H), 0.81 (m, 6H).

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
  7. customPurification of the residue by column chromatography (eluent 30% MeOH in EtOAc)

Sources & evidence

ORD record
ord-6b0d0ae794454df0a480e712135ab26c
Source dataset
uspto-grants-2014_06
Patent number
US08759522B2

Reaction notes

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