Diisopropylethylamine → [(S)-1-(7-bromo-6-fluoro-1-pyridin-2-yl-1H-benzoimidazol-2-yl)ethyl]-[9-(tetrahydro-pyran-2-yl)-9H-purin-6-yl]amine

HRID 243057Notes

Reaction equation

HRID 243057 reaction equation
C(OC(=O)[NH:7][C@H:8]([C:10]1[N:14]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)[C:13]2[C:21]([Br:26])=[C:22]([F:25])[CH:23]=[CH:24][C:12]=2[N:11]=1)[CH3:9])(C)(C)C.Cl[C:29]1[N:37]=[CH:36][N:35]=[C:34]2[C:30]=1[N:31]=[CH:32][N:33]2[CH:38]1[CH2:43][CH2:42][CH2:41][CH2:40][O:39]1.CCN(C(C)C)C(C)C>Cl.O1CCOCC1>[Br:26][C:21]1[C:13]2[N:14]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=3)[C:10]([C@@H:8]([NH:7][C:29]3[N:37]=[CH:36][N:35]=[C:34]4[C:30]=3[N:31]=[CH:32][N:33]4[CH:38]3[CH2:43][CH2:42][CH2:41][CH2:40][O:39]3)[CH3:9])=[N:11][C:12]=2[CH:24]=[CH:23][C:22]=1[F:25]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 68157947[(S)-1-(7-Bromo-6-fluoro-1-pyridin-2-yl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tert-butyl ester

Product 1

HCID 68179439[(S)-1-(7-bromo-6-fluoro-1-pyridin-2-yl-1H-benzoimidazol-2-yl)ethyl]-[9-(tetrahydro-pyran-2-yl)-9H-purin-6-yl]amineYield 76%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

[(S)-1-(7-Bromo-6-fluoro-1-pyridin-2-yl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tert-butyl ester (220 mg, 0.66 mmol) was dissolved in hydrochloric acid in dioxane (15 mL, 4M) and the reaction stirred at RT for 1 h. The reaction mixture was concentrated in vacuo then the residue dissolved in IPA and 6-chloro-9-(tetrahydro-pyran-2-yl)-9H-purine (203 mg, 0.85 mmol) and DIPEA (168 μL, 0.99 mmol) added. The reaction mixture was heated at 90° C. for 16 h then concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, eluting with 0-100% methanol in EtOAc) to yield the title compound as a white solid (267 mg, 76%). LCMS (Method C): RT=3.01 min, [M+H]+=537+538.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionthe residue dissolved in IPA
  3. temperatureThe reaction mixture was heated at 90° C. for 16 h
  4. concentrationthen concentrated in vacuo
  5. washThe resultant residue was subjected to flash chromatography (SiO2, eluting with 0-100% methanol in EtOAc)

Sources & evidence

ORD record
ord-b2134f440ea143428ccd7d1f51c8ba2f
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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