Diisopropylethylamine → HCID 178461961, compound

HRID 243479Notes

Reaction equation

HRID 243479 reaction equation
[F:1][C:2]1[CH2:11][CH2:10][C:9]2[CH2:8][CH2:7][N:6]3[C:12]([C@@H:15]([NH2:17])[CH3:16])=[N:13][CH:14]=[C:4]([C:5]=23)[CH:3]=1.Cl[C:19]1[N:27]=[CH:26][N:25]=[C:24]2[C:20]=1[N:21]=[CH:22][N:23]2C1CCCCO1.CCN(C(C)C)C(C)C>C(O)CCC>[F:1][C:2]1[CH2:11][CH2:10][C:9]2[CH2:8][CH2:7][N:6]3[C:12]([C@@H:15]([NH:17][C:19]4[N:27]=[CH:26][N:25]=[C:24]5[C:20]=4[N:21]=[CH:22][NH:23]5)[CH3:16])=[N:13][CH:14]=[C:4]([C:5]=23)[CH:3]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 68158063(S)-1-(5-Fluoro-6,7,8,9-tetrahydro-2,9a-diazabenzo[cd]azulen-1-yl)ethylamine

Product 1

HCID 178461961HCID 178461961, compoundYield 69.1%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of (S)-1-(5-fluoro-6,7,8,9-tetrahydro-2,9a-diazabenzo[cd]azulen-1-yl)ethylamine (70 mg, 0.30 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (71.8 mg, 0.30 mmol), and DIPEA (0.153 mL, 0.90 mmol) in n-butanol (1.5 mL) was stirred in a sealed vial at 90° C. for 16 h. After cooling to RT, volatiles were removed under reduced pressure. The residue was dissolved in MeOH (5 mL) and cooled in an ice bath. HCl in isopropanol (1.25 M, 3 mL) was added and the mixture stirred at 0° C. for 1.5 h and then concentrated under reduced pressure. The residue was dissolved in MeOH and loaded onto an Isolute® SCX-2 cartridge. The cartridge was washed with MeOH and the product eluted with 0.5 M NH3 in MeOH, further purification by column chromatography (Si—PCC, gradient 2-12% 2M NH3/MeOH in DCM) afforded 405 as a white solid (72.8 mg, 69%). LCMS (Method K): RT 2.68 min [M+H]+ 352.0. 1H NMR ((CD3)2SO, 400 MHz): 12.93 (1H, bs), 8.24 (1H, s), 8.15 (1H, s), 7.89 (1H, d, J=7.9 Hz), 7.43 (1H, dd, J=8.7, 4.8 Hz), 6.99 (1H, dd, J=10.8, 8.8 Hz), 5.83 (1H, bs), 4.31-4.29 (2H, m), 3.04-3.01 (2H, m), 2.08-1.94 (4H, m), 1.66 (3H, d, J=6.7 Hz)

Workup

  1. temperatureAfter cooling to RT
  2. customvolatiles were removed under reduced pressure
  3. dissolutionThe residue was dissolved in MeOH (5 mL)
  4. temperaturecooled in an ice bath
  5. additionHCl in isopropanol (1.25 M, 3 mL) was added
  6. stirringthe mixture stirred at 0° C. for 1.5 h
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe residue was dissolved in MeOH
  9. washThe cartridge was washed with MeOH
  10. washthe product eluted with 0.5 M NH3 in MeOH, further purification by column chromatography (Si—PCC, gradient 2-12% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-80c50579f574443b93f3ec99f7dd73b9
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

Loading…