Diisopropylethylamine → HCID 178462636, compound

HRID 243486Notes

Reaction equation

HRID 243486 reaction equation
[CH2:1]([N:3]1[C:7]2[C:8]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=3)=[C:9]([F:12])[CH:10]=[CH:11][C:6]=2[N:5]=[C:4]1[C@@H:19]([NH2:21])[CH3:20])[CH3:2].Cl[C:23]1[N:31]=[CH:30][N:29]=[C:28]2[C:24]=1[N:25]=[CH:26][N:27]2C1CCCCO1.CCN(C(C)C)C(C)C>>[CH2:1]([N:3]1[C:7]2[C:8]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=3)=[C:9]([F:12])[CH:10]=[CH:11][C:6]=2[N:5]=[C:4]1[C@@H:19]([NH:21][C:23]1[N:31]=[CH:30][N:29]=[C:28]2[C:24]=1[N:25]=[CH:26][NH:27]2)[CH3:20])[CH3:2]

Participants

4

Reactant 3

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 68157537HCID 68157537, compound

Product 1

HCID 178462636HCID 178462636, compoundYield 31.1%

Conditions

Temperature
90 °C

Procedure

A mixture of (S)-1-(1-ethyl-6-fluoro-7-pyridin-2-yl-1H-benzoimidazol-2-yl)ethylamine (0.203 g, 0.715 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (145 mg, 0.60 mmol) and DIPEA (543 μL, 3.0 mmol) were added and the reaction mixture heated at 90° C. for 16 hours. The reaction mixture was loaded onto an SCX column to remove the THP group. The column was washed with MeOH and the product was eluted with 2M NH3 in MeOH. The product fractions were collected, concentrated in vacuo and the resultant residue was subjected to flash chromatography (Si—PPC, gradient 0-7% MeOH in DCM) to give 412 as a white solid (75 mg, 25%). LCMS (Method K): RT 2.76 min [M+H]+ 403. 1H NMR (DMSO, 400 MHz): δ 12.83 (1H, br s), 8.68 (1H, d, J=4.8 Hz), 8.12 (2H, d, J=14.3 Hz), 7.95 (1H, br s), 7.91 (1H, td, J=7.7, 1.7 Hz), 7.68-7.62 (2H, m), 7.46 (1H, d, J=7.2, 5.0 Hz), 7.11 (1H, dd, J=10.4, 9.0 Hz), 5.78-5.67 (1H, m), 3.91-3.71 (2H, m), 1.63 (3H, d, J=6.8 Hz), 0.71 (3H, t, J=6.9 Hz)

Workup

  1. additionwere added
  2. customto remove the THP group
  3. washThe column was washed with MeOH
  4. washthe product was eluted with 2M NH3 in MeOH
  5. customThe product fractions were collected
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-514677035c9744099c0eb2c7cf8708b4
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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