Diisopropylethylamine → HCID 178461901, compound

HRID 243299Notes

Reaction equation

HRID 243299 reaction equation
[O:1]1[CH2:6][CH2:5][CH2:4][CH:3]([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])[CH2:2]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[CH2:6][CH2:5][CH2:4][CH:3]([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])[CH2:2]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 68157342(S)-1-[1-(tetrahydropyran-3-yl)-1H-benzoimidazol-2-yl]ethylamine

Product 1

HCID 178461901HCID 178461901, compoundYield 71.1%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (S)-1-[1-(tetrahydropyran-3-yl)-1H-benzoimidazol-2-yl]ethylamine from Example 18 (295 mg, 1.20 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (400 mg, 1.68 mmol) and DIPEA (0.38 mL, 2.16 mmol) in n-butanol (2 mL) was stirred in a sealed vial for 16 h at 100° 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. Purification by Isolute® SCX-2 was repeated a second time and then the resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM) affording 128 as a white solid (310 mg, 71%). LCMS: RT 2.42 and 2.46 min [M+H]+ 364.0. 1H NMR (DMSO, 400 MHz): δ 8.38-7.88 (3H, m), 7.80 (1H, t, J=8.38 Hz), 7.65-7.54 (1H, m), 7.21-7.09 (2H, m), 5.95 (1H, br), 4.71-4.57 (1H, m), 4.14-4.04 (1H, m), 4.00-3.86 (1H, m), 3.83-3.71 (1H, m), 3.55-3.43 (1H, m), 3.16 (0.5H, d, J=4.68 Hz), 2.56-2.43 (0.5H, m), 2.36-2.23 (0.5H, m), 2.02 (0.5H, br), 1.83-1.72 (4H, m), 1.56 (0.5H, bd, J=13.68 Hz), 1.24-1.08 (0.5H, m). Signals split due to presence of rotamers/tautomers

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. customPurification by Isolute® SCX-2
  8. customthe resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-2eeeff23904c4bdb8bbedcc623f7c891
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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