Hydrochloric Acid → HCID 178429741, compound

HRID 243359Notes

Reaction equation

HRID 243359 reaction equation
Cl.Cl.[F:3][C:4]1[CH:5]=[CH:6][C:7]2[N:11]=[C:10]([C@@H:12]([NH2:14])[CH3:13])[N:9]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:8]=2[C:21]=1[CH3:22].Cl[C:24]1[N:32]=[CH:31][N:30]=[C:29]2[C:25]=1[N:26]=[CH:27][N:28]2C1CCCCO1.CCN(C(C)C)C(C)C.Cl>C(O)CCC.O1CCOCC1>[F:3][C:4]1[CH:5]=[CH:6][C:7]2[N:11]=[C:10]([C@@H:12]([NH:14][C:24]3[N:32]=[CH:31][N:30]=[C:29]4[C:25]=3[N:26]=[CH:27][NH:28]4)[CH3:13])[N:9]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:8]=2[C:21]=1[CH3:22]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 68157596(S)-1-(6-fluoro-7-methyl-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride

Product 1

HCID 178429741HCID 178429741, compoundYield 70%

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of (S)-1-(6-fluoro-7-methyl-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride (330 mg, 1.23 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (351 mg, 1.47 mmol) and DIPEA (320 μL, 2.45 mmol) in n-butanol (6 mL) was heated at 90° C. in a sealed vial for 18 h. After cooling to RT, the volatiles were removed under reduced pressure and the resulting residue purified by column chromatography (Si—PCC, gradient 0-10% MeOH in EtOAc). A solution of the compound thus obtained in MeOH (5 mL) and 4N HCl in dioxane (1 ml) was stirred at RT for 1 h then the volatiles were removed under reduced pressure. The resulting residue was partitioned between EtOAc and a saturated solution of NaHCO3. A white solid precipitated and was collected by filtration to afford 183 (333 mg, 70%). LCMS (Method K): RT 3.46 min [M+H]+ 388.1. 1H NMR (DMSO-d6, 400 MHz): δ 12.55 (1H, s), 8.06-8.00 (2H, m), 7.71-7.39 (7H, m), 7.05 (1H, dd, J=10.58, 8.77 Hz), 5.30 (1H, br s), 1.70 (3H, d, J=1.84 Hz), 1.53 (3H, d, J=6.84 Hz)

Workup

  1. temperatureAfter cooling to RT
  2. customthe volatiles were removed under reduced pressure
  3. customthe resulting residue purified by column chromatography (Si—PCC, gradient 0-10% MeOH in EtOAc)
  4. customA solution of the compound thus obtained in MeOH (5 mL)
  5. customthe volatiles were removed under reduced pressure
  6. customThe resulting residue was partitioned between EtOAc
  7. customA white solid precipitated
  8. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-a3d0b6c5419345c3b5fd344e6f0450e5
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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