Diisopropylethylamine → HCID 178456316, compound

HRID 243483Notes

Reaction equation

HRID 243483 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C@@H:10]([NH2:12])[CH3:11])[N:7]([CH:13]([CH3:15])[CH3:14])[C:6]=2[C:16]=1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=1.Cl[C:24]1[N:32]=[CH:31][N:30]=[C:29]2[C:25]=1[N:26]=[CH:27][N:28]2C1CCCCO1.CCN(C(C)C)C(C)C>>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:9]=[C:8]([C@@H:10]([NH:12][C:24]3[N:32]=[CH:31][N:30]=[C:29]4[C:25]=3[N:26]=[CH:27][NH:28]4)[CH3:11])[N:7]([CH:13]([CH3:14])[CH3:15])[C:6]=2[C:16]=1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=1

Participants

4

Reactant 3

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 68157198HCID 68157198, compound

Product 1

HCID 178456316HCID 178456316, compoundYield 10%

Conditions

Temperature
90 °C

Procedure

(S)-1-(6-Fluoro-1-isopropyl-7-pyridin-2-yl-1H-benzoimidazol-2-yl)ethylamine (0.18 g, 0.6 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 (SiO2, eluting with 0-10% methanol in DCM) to give 409 as a white solid (23 mg, 10%). LCMS (Method K): RT 2.94 min [M+H]+ 417. 1H NMR (DMSO-d6, 400 MHz): δ 12.69 (1H, br s), 8.69 (1H, d, J=4.4 Hz), 8.17 (1H, br s), 8.13 (1H, s), 7.93 (1H, td, J=7.8, 1.8 Hz), 7.66 (1H, dd, J=8.8, 5.0 Hz), 7.64 (1H, br s), 7.62 (1H, d, J=7.8 Hz), 7.47 (1H, ddd, J=7.7, 4.9, 1.1 Hz), 7.11 (1H, dd, J=10.2, 8.9 Hz), 5.90-5.78 (1H, m), 4.11-3.87 (1H, m), 1.62 (3H, d, J=6.6 Hz), 1.35-1.15 (6H, m)

Workup

  1. customto remove the THP group
  2. washThe column was washed with MeOH
  3. washthe product was eluted with 2M NH3 in MeOH
  4. customThe product fractions were collected
  5. concentrationconcentrated in vacuo
  6. washthe resultant residue was subjected to flash chromatography (SiO2, eluting with 0-10% methanol in DCM)

Sources & evidence

ORD record
ord-494bdf2dbfd847fda96e20c114cdc021
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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