Diisopropylethylamine → HCID 178461930, compound

HRID 243373Notes

Reaction equation

HRID 243373 reaction equation
[CH:1]1([N:7]2[C:11]3[CH:12]=[C:13]([F:16])[CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[C@@H:17]([NH2:19])[CH3:18])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]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>[CH:1]1([N:7]2[C:11]3[CH:12]=[C:13]([F:16])[CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[C@@H:17]([NH:19][C:21]2[N:29]=[CH:28][N:27]=[C:26]3[C:22]=2[N:23]=[CH:24][NH:25]3)[CH3:18])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 68157781HCID 68157781, compound

Product 1

HCID 178461930HCID 178461930, compound

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
100 °C

Procedure

(S)-1-(1-Cyclohexyl-6-fluoro-1H-benzoimidazol-2-yl)ethylamine (0.41 g, 1.56 mmol) was dissolved in n-butanol (5 mL) and 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (0.374 g, 1.56 mmol) and DIPEA (1.38 mL, 7.82 mmol) added. The reaction mixture was heated to 100° C. overnight. The resultant mixture was allowed to cool to RT and was concentrated in vacuo. The residue was passed down an Isolute® SCX-2 cartridge, eluting with DCM, MeOH and 2M NH3 in MeOH to afford crude product. This was purified by column chromatography (silica gel, gradient 0-10% MeOH in DCM) to afford 201 as a pale yellow gum, which solidified on standing (204 mg, 35%). LCMS (Method K): RT 3.31 min [M+H]+ 380.1 1H NMR (DMSO-d6, 400 MHz): δ 8.30 (1H, s), 8.15 (1H, s), 8.04 (1H, s), 7.66-7.54 (2H, m), 7.02 (1H, td, J=9.29, 2.34 Hz), 6.00 (1H, s), 4.51-4.37 (1H, m), 2.27-2.13 (1H, m), 2.07-1.95 (1H, m), 1.88-1.75 (2H, m), 1.70 (3H, d, J=6.70 Hz), 1.64-1.44 (3H, m), 1.39-1.26 (2H, m), 0.75-0.57 (1H, m)

Workup

  1. temperatureto cool to RT
  2. concentrationwas concentrated in vacuo
  3. washeluting with DCM, MeOH and 2M NH3 in MeOH
  4. customto afford crude product
  5. customThis was purified by column chromatography (silica gel, gradient 0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-299ffeedf62c4e8e9a23fb140b5ec64e
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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