Diisopropylethylamine → HCID 178461960, compound

HRID 243306Notes

Reaction equation

HRID 243306 reaction equation
[F:1][C:2]1[C:10]2[N:9]=[C:8]([C@@H:11]([NH2:13])[CH3:12])[N:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1.Cl[C:21]1[N:29]=[CH:28][N:27]=[C:26]2[C:22]=1[N:23]=[CH:24][N:25]2C1CCCCO1.CCN(C(C)C)C(C)C>C(O)CCC>[F:1][C:2]1[C:10]2[N:9]=[C:8]([C@@H:11]([NH:13][C:21]3[N:29]=[CH:28][N:27]=[C:26]4[C:22]=3[N:23]=[CH:24][NH:25]4)[CH3:12])[N:7]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 68156990(1S)-1-(4-Fluoro-1-phenyl-1H-benzimidazol-2-yl)ethan-1-amine

Product 1

HCID 178461960HCID 178461960, compound

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (S)-1-(4-fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine from Example 15 (0.407 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (122 mg, 0.509 mmol) and DIPEA (0.444 mL, 2.55 mmol) in n-butanol (3 mL) was stirred in a sealed vial for 20 h at 100° C. After cooling to RT, volatiles were removed under reduced pressure and the resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in EtOAc). The product containing fractions were concentrated in vacuo and the resulting residue was dissolved in EtOAc (10 mL) and stirred with 2N HCl (10 mL) for 15 min. Volatiles were removed under reduced pressure and the residue was dissolved in MeOH (2 mL) and triturated with diethyl ether affording 136 as a beige powder (126 mg, 78%). LCMS: RT 3.47 min [M+H]+ 374.0. 1H NMR (DMSO, 400 MHz): δ 10.03 (1H, s), 8.66 (1H, s), 8.55 (1H, s), 7.68-7.38 (5H, m), 7.28-7.21 (1H, m), 7.13 (1H, dd, J=10.91, 7.98 Hz), 6.94 (1H, dd, J=8.11, 0.82 Hz), 5.68-5.59 (1H, m), 1.72 (3H, d, J=6.85 Hz)

Workup

  1. temperatureAfter cooling to RT
  2. customvolatiles were removed under reduced pressure
  3. customthe resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% MeOH in EtOAc)
  4. additionThe product containing fractions
  5. concentrationwere concentrated in vacuo
  6. dissolutionthe resulting residue was dissolved in EtOAc (10 mL)
  7. stirringstirred with 2N HCl (10 mL) for 15 min
  8. customVolatiles were removed under reduced pressure
  9. dissolutionthe residue was dissolved in MeOH (2 mL)
  10. customtriturated with diethyl ether affording 136 as a beige powder (126 mg, 78%)

Sources & evidence

ORD record
ord-5f506e14ab0442fb99174633a79d2700
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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