Diisopropylethylamine → HCID 90405227, compound

HRID 1505644Notes

Reaction equation

HRID 1505644 reaction equation
Cl[C:2]1[C:3]2[CH:10]=[C:9]([CH2:11][C:12]([F:15])([F:14])[F:13])[S:8][C:4]=2[N:5]=[CH:6][N:7]=1.C(N(CC)C(C)C)(C)C.C([N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1)(OC(C)(C)C)=O>Cl.O1CCOCC1>[N:32]1([C:2]2[C:3]3[CH:10]=[C:9]([CH2:11][C:12]([F:15])([F:14])[F:13])[S:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 904050864-Chloro-6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidine

Product 1

HCID 90405227HCID 90405227, compoundYield 66.2%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

190 mg of 4-chloro-6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidine (0.75 mmol) was added to a stirred solution of 290 mg of N,N-diisopropylethylamine (2.25 mmol) and 168 mg of 1-Boc-piperazine (0.9 mmol) in 20 mL and was heated at reflux overnight. Solvent was removed under reduced pressure and the residue was loaded on silica gel column. Elution with DCM:MeOH produced 215 mg of Boc-intermediate as a pale yellow solid. Later it was dissolved in 20 mL of 4M HCl in dioxane and stirred for 2 hs. Solvent was evaporated under reduced pressure and the residue was partitioned between ethyl acetate and saturated sodium carbonate solution. Organic layer was washed with brine, dried over MgSO4 and evaporated to afford 150 mg of 4-(piperazin-1-yl)-6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidine, which was used in the next step without purification.

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight
  3. customSolvent was removed under reduced pressure
  4. washElution with DCM
  5. customMeOH produced 215 mg of Boc-intermediate as a pale yellow solid
  6. customSolvent was evaporated under reduced pressure
  7. customthe residue was partitioned between ethyl acetate and saturated sodium carbonate solution
  8. washOrganic layer was washed with brine
  9. dry with materialdried over MgSO4
  10. customevaporated

Sources & evidence

ORD record
ord-1460d0753808489f8dba0974cdea7705
Source dataset
uspto-grants-2015_12
Patent number
US09216993B2

Reaction notes

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