Diisopropylethylamine → HCID 178461954, compound

HRID 243436Notes

Reaction equation

HRID 243436 reaction equation
C(OC(=O)[NH:7][C@H:8]([C:10]1[N:14]([C:15]2[CH:16]=[N:17][CH:18]=[C:19]([F:21])[CH:20]=2)[C:13]2[C:22]([C:27]#[N:28])=[C:23]([F:26])[CH:24]=[CH:25][C:12]=2[N:11]=1)[CH3:9])(C)(C)C.Cl[C:31]1[N:39]=[CH:38][N:37]=[C:36]2[C:32]=1[N:33]=[CH:34][N:35]2C1CCCCO1.CCN(C(C)C)C(C)C>Cl.O1CCOCC1.CO>[F:26][C:23]1[CH:24]=[CH:25][C:12]2[N:11]=[C:10]([C@@H:8]([NH:7][C:31]3[N:39]=[CH:38][N:37]=[C:36]4[C:32]=3[N:33]=[CH:34][NH:35]4)[CH3:9])[N:14]([C:15]3[CH:16]=[N:17][CH:18]=[C:19]([F:21])[CH:20]=3)[C:13]=2[C:22]=1[C:27]#[N:28]

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 68158144{(S)-1-[7-Cyano-6-fluoro-1-(5-fluoropyridin-3-yl)-1H-benzoimidazol-2-yl]-ethyl}carbamic acid tert-butyl ester

Product 1

HCID 178461954HCID 178461954, compoundYield 29.3%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolvent2×HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

{(S)-1-[7-Cyano-6-fluoro-1-(5-fluoropyridin-3-yl)-1H-benzoimidazol-2-yl]-ethyl}carbamic acid tert-butyl ester (215 mg, 0.54 mmol) was dissolved in HCl in dioxane (4N, 5 mL) and the reaction mixture stirred at RT for 1 hour. The mixture was concentrated in vacuo and the residue dissolved in IPA (5 mL). 6-Chloro-9-(tetrahydropyran-2-yl)-9H-purine (167 mg, 0.70 mmol) and DIPEA (275 μL, 1.61 mmol) were added and the reaction mixture heated at 90° C. for 16 hours. The reaction mixture was concentrated in vacuo and the resultant residue was subjected to flash chromatography (SiO2, eluting with 0-10% methanol in EtOAc) to give an off white solid LCMS (Method C): RT=2.89 min, [M+H]+=502. The solid was dissolved in HCl in methanol (1.25 M, 5 mL) and the reaction mixture stirred at RT for 10 min. The reaction mixture was concentrated in vacuo and the resultant residue subjected to prep. HPLC (C18 phenomenex column, 10-90% MeCN in water 0.1% formic acid, 20 min gradient) to give 346 as a white solid (66 mg, 29%). 1H NMR 300 MHz δ (d6-DMSO): 12.91 (1H, br s), 8.89-8.46 (2H, m), 8.44-7.85 (5H, m), 7.42 (1H, t, J=9.6 Hz), 5.65-5.37 (1H, m), 1.67 (3H, t, J=6.8 Hz), LCMS (Method K): RT=3.03 min, [M+H]+=418

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. dissolutionthe residue dissolved in IPA (5 mL)
  3. temperaturethe reaction mixture heated at 90° C. for 16 hours
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. washthe resultant residue was subjected to flash chromatography (SiO2, eluting with 0-10% methanol in EtOAc)
  6. customto give an off white solid LCMS (Method C)
  7. stirringthe reaction mixture stirred at RT for 10 min
  8. concentrationThe reaction mixture was concentrated in vacuo

Sources & evidence

ORD record
ord-199aea9b3baf42e4aaee74e703e3692d
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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