Hydrochloric Acid → HCID 25222665, compound

HRID 38572Notes

Reaction equation

HRID 38572 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:11]3[C:18]4[CH2:19][CH2:20][N:21]([C:23](=[O:38])/[CH:24]=[CH:25]/[C@@H:26]5[CH2:30][CH2:29][CH2:28][N:27]5C(OC(C)(C)C)=O)[CH2:22][C:17]=4[S:16][C:12]=3[N:13]=[CH:14][N:15]=2)[CH:5]=[CH:6][C:7]=1[F:8].Cl>CC(O)C.O1CCOCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[C:11]3[C:18]4[CH2:19][CH2:20][N:21]([C:23](=[O:38])/[CH:24]=[CH:25]/[C@@H:26]5[CH2:30][CH2:29][CH2:28][NH:27]5)[CH2:22][C:17]=4[S:16][C:12]=3[N:13]=[CH:14][N:15]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 58116987tert-Butyl (2S)-2-[(1E)-3-{4-[(3-chloro-4-fluorophenyl)amino]-5,8-dihydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-7(6H)-yl}-3-oxoprop-1-en-1-yl]pyrrolidine-1-carboxylate

Product 1

HCID 25222665HCID 25222665, compoundYield 42.6%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

tert-Butyl (2S)-2-[(1E)-3-{4-[(3-chloro-4-fluorophenyl)amino]-5,8-dihydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidin-7(6H)-yl}-3-oxoprop-1-en-1-yl]pyrrolidine-1-carboxylate from Example 14A (397 mg, 0.712 mmol) was dissolved in 2-propanol (4 mL), and a 4 M solution of gaseous hydrogen chloride in dioxane (0.36 mL) was added. The mixture was stirred for 3 h at 70° C. The solvent was then removed in vacuo. The residue was dissolved in ethyl acetate and washed with 1 N aqueous sodium hydroxide solution. The organic layer was dried over sodium sulfate, and the solvent was evaporated. The crude product was purified by preparative HPLC to yield 139 mg (42%) of the title compound.

Workup

  1. customThe solvent was then removed in vacuo
  2. dissolutionThe residue was dissolved in ethyl acetate
  3. washwashed with 1 N aqueous sodium hydroxide solution
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. customthe solvent was evaporated
  6. customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-f747e8c5fde847d7b622aed2ceca3956
Source dataset
uspto-grants-2013_09
Patent number
US08524722B2

Reaction notes

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