Triethylamine → HCID 87076616, compound

HRID 2403351Notes

Reaction equation

HRID 2403351 reaction equation
C([N:8]1[CH2:13][CH2:12][NH:11][C:10](=[O:14])[CH2:9]1)(OC(C)(C)C)=O.[H-].[Na+].Br[CH2:18][C:19]1[S:27][C:26]2[C:25]([N:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)=[N:24][C:23]([Cl:34])=[N:22][C:21]=2[CH:20]=1.CCN(CC)CC.[CH3:42][S:43](Cl)(=[O:45])=[O:44]>CN(C=O)C.C(Cl)Cl>[Cl:34][C:23]1[N:24]=[C:25]([N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)[C:26]2[S:27][C:19]([CH2:18][N:11]3[CH2:12][CH2:13][N:8]([S:43]([CH3:42])(=[O:45])=[O:44])[CH2:9][C:10]3=[O:14])=[CH:20][C:21]=2[N:22]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 24758Sodium hydrideHCID 31297Methanesulfonyl chlorideHCID 3157178Tert-butyl 3-oxopiperazine-1-carboxylateHCID 461807264-(6-(Bromomethyl)-2-chlorothieno[3,2-d]pyrimidin-4-yl)morpholine

Product 1

HCID 87076616HCID 87076616, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-BOC-piperazinone (0.3 g, 1.6 mmol) in DMF (3 mL) at 0° C. was added NaH (60% in mineral oil, 1.9 mmol). Next, 6-(bromomethyl)-2-chloro-4-morpholinothieno[3,2-d]pyrimidine (0.6 g, 2 mmol) was added and the reaction stirred for 15 min. The reaction was quenched with saturated NH4Cl and the aqueous layer was extracted with EtOAc. The combined organics were dried over Na2SO4 and concentrated in vacuo. This intermediate was dissolved in CH2Cl2 (40 mL) and MeOH (40 mL) and Et2O (10 mL) and cooled to 0° C. To this solution was added 4 M HCl in dioxane (20 mL). The reaction was warmed to room temperature, stirred 18 h, then was concentrated in vacuo. To the residue was added CH2Cl2 (50 mL), Et3N (1.5 mL, 11 mmol), and MeSO2Cl (0.6 mL, 8 mmol). The reaction mixture stirred 42 h at room temperature. The reaction was quenched with water and extracted with EtOAc. The combined organics were dried over Na2SO4 and concentrated in vacuo (0.25 g, 28% over 3 steps). MS (Q1) 446 (M)+

Workup

  1. customThe reaction was quenched with saturated NH4Cl
  2. extractionthe aqueous layer was extracted with EtOAc
  3. dry with materialThe combined organics were dried over Na2SO4
  4. concentrationconcentrated in vacuo
  5. dissolutionThis intermediate was dissolved in CH2Cl2 (40 mL)
  6. additionTo this solution was added 4 M HCl in dioxane (20 mL)
  7. temperatureThe reaction was warmed to room temperature
  8. stirringstirred 18 h
  9. concentrationwas concentrated in vacuo
  10. stirringThe reaction mixture stirred 42 h at room temperature
  11. customThe reaction was quenched with water
  12. extractionextracted with EtOAc
  13. dry with materialThe combined organics were dried over Na2SO4
  14. concentrationconcentrated in vacuo (0.25 g, 28% over 3 steps)

Sources & evidence

ORD record
ord-a4c55de1749643c691f963de7d4bc847
Source dataset
uspto-grants-2014_08
Patent number
US08802670B2

Reaction notes

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