Diisopropylethylamine → HCID 178461908, compound

HRID 243298Notes

Reaction equation

HRID 243298 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[C@@H:16]([NH2:18])[CH3:17])[CH2:3][CH2:2]1.Cl[C:20]1[N:28]=[CH:27][N:26]=[C:25]2[C:21]=1[N:22]=[CH:23][N:24]2C1CCCCO1.CCN(C(C)C)C(C)C>C(O)CCC>[O:1]1[CH2:2][CH2:3][CH:4]([N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[C@@H:16]([NH:18][C:20]2[N:28]=[CH:27][N:26]=[C:25]3[C:21]=2[N:22]=[CH:23][NH:24]3)[CH3:17])[CH2:5][CH2:6]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 68157794HCID 68157794, compound

Product 1

HCID 178461908HCID 178461908, compound

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of (S)-1-[1-(tetrahydropyran-4-yl)-1H-benzoimidazol-2-yl]ethylamine from Example 17 (195 mg, 0.796 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (266 mg, 1.11 mmol) and DIPEA (0.25 mL, 1.43 mmol) in n-butanol (2 mL) was stirred in a sealed vial for 3 days at 120° C. After cooling to RT, volatiles were removed under reduced pressure and the resulting residue was loaded into an Isolute® SCX-2 which was washed with MeOH and the product eluted with 2M NH3/MeOH. The product containing fractions were combined and concentrated in vacuo and the resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM) and then triturated with a mixture EtOAc and MeOH affording 127 as an off-white solid (148 mg, 51%). LCMS: RT 2.29 min [M+H]+ 364.0. 1H NMR (DMSO, 400 MHz): δ 12.93 (1H, bs), 8.30-7.81 (3H, m), 7.61-7.59 (2H, m), 7.17-7.03 (2H, m), 5.96 (1H, bs), 4.81-4.63 (1H, m), 3.94 (1H, d, J=11.07 Hz), 3.74 (1H, d, J=11.25 Hz), 3.35 (1H, bs), 2.84 (1H, bs), 2.47-2.35 (1H, m), 2.30-2.17 (1H, m), 1.75 (1H, bd), 1.64 (3H, d, J=6.71 Hz), 1.50 (1H, bs)

Workup

  1. temperatureAfter cooling to RT
  2. customvolatiles were removed under reduced pressure
  3. washwas washed with MeOH
  4. washthe product eluted with 2M NH3/MeOH
  5. additionThe product containing fractions
  6. concentrationconcentrated in vacuo
  7. customthe resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM)
  8. customtriturated with a mixture EtOAc and MeOH affording 127 as an off-white solid (148 mg, 51%)

Sources & evidence

ORD record
ord-cf9039d87f3a41a5a34687191f495612
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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