Hydrochloric Acid → HCID 68158153, compound

HRID 243155Notes

Reaction equation

HRID 243155 reaction equation
C(O[C:6](=O)[NH:7][C@H:8]([C:10](=[O:26])[NH:11][C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=1[NH:19][C:20]1[CH:25]=[CH:24][N:23]=[CH:22][N:21]=1)[CH3:9])(C)(C)C.Cl.ClC1[N:38]=[CH:37][N:36]=[C:35]2[C:31]=1[N:32]=[CH:33][N:34]2[CH:39]1[CH2:44][CH2:43][CH2:42][CH2:41][O:40]1.CCN(C(C)C)C(C)C>O1CCOCC1.CC(O)C.CCOC(C)=O>[F:18][C:15]1[CH:16]=[CH:17][C:12]([NH:11][C:10](=[O:26])[C@@H:8]([NH:7][C:6]2[N:38]=[CH:37][N:36]=[C:35]3[C:31]=2[N:32]=[CH:33][N:34]3[CH:39]2[CH2:44][CH2:43][CH2:42][CH2:41][O:40]2)[CH3:9])=[C:13]([NH:19][C:20]2[CH:25]=[CH:24][N:23]=[CH:22][N:21]=2)[CH:14]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 68157566HCID 68157566, compound

Product 1

HCID 68158153HCID 68158153, compoundYield 51%

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

{(S)-1-[4-Fluoro-2-(pyrimidin-4-ylamino)phenylcarbamoyl]ethyl}carbamic acid tert-butyl ester (0.27 g, 0.72 mmol) was treated with 4M HCl in dioxane (10 mL) for 45 min at 20° C. The solvent was removed by evaporation under reduced pressure to give a solid, (0.29 g). 0.145 g of this solid was treated in a sealed tube with 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (103 mg, 0.43 mmol) and DIPEA (0.25 mL), 1.44 mmol) in IPA (1.5 mL) at 80° C. under argon for 16 h. The reaction mixture was diluted with EtOAc (20 mL) and washed with water (5 mL). The aqueous layer was extracted with EtOAc (10 mL). The combined organic extracts were dried (Na2SO4), concentrated in vacuo and purified by column chromatography (Si—PCC, gradient 0-10% (9:1 MeOH/0.880 NH3) in DCM) to give the title compound as an orange gum, (88 mg, 51%). LCMS (Method B): RT 1.99 min [M+H]+ 478.13

Workup

  1. customThe solvent was removed by evaporation under reduced pressure
  2. customto give a solid, (0.29 g)
  3. washwashed with water (5 mL)
  4. extractionThe aqueous layer was extracted with EtOAc (10 mL)
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. custompurified by column chromatography (Si—PCC, gradient 0-10% (9:1 MeOH/0.880 NH3) in DCM)

Sources & evidence

ORD record
ord-ec43cecb767e492e82e6c5b0fa9a9942
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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