Diisopropylethylamine → HCID 178461933, compound

HRID 243473Notes

Reaction equation

HRID 243473 reaction equation
[NH2:1][C@H:2]([C:4]1[N:8]([CH:9]2[CH2:12][CH:11]([C:13]#[N:14])[CH2:10]2)[C:7]2[CH:15]=[C:16]([F:19])[CH:17]=[CH:18][C:6]=2[N:5]=1)[CH3:3].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>CC(O)C>[F:19][C:16]1[CH:17]=[CH:18][C:6]2[N:5]=[C:4]([C@@H:2]([NH:1][C:21]3[N:29]=[CH:28][N:27]=[C:26]4[C:22]=3[N:23]=[CH:24][NH:25]4)[CH3:3])[N:8]([CH:9]3[CH2:12][CH:11]([C:13]#[N:14])[CH2:10]3)[C:7]=2[CH:15]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 68158146HCID 68158146, compound

Product 1

HCID 178461933HCID 178461933, compoundYield 32.1%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

3-[2-((S)-1-Aminoethyl)-6-fluorobenzoimidazol-1-yl]cyclobutanecarbonitrile (0.075 g, 0.29 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (0.070 g, 0.29 mmol) and DIPEA (0.26 mL, 1.45 mmol) in 2-propanol (5 mL) was stirred at 90° C. in a sealed microwave tube for 16 hours. After cooling, the reaction mixture was concentrated in vacuo and the residue loaded onto an Isolute® SCX-2 cartridge which was washed with DCM and MeOH, then the product eluted with 2M NH3/MeOH then concentrated in vacuo. The residue was purified by silica gel chromatography, eluting with 100% DCM—10% methanol in DCM to give 399 as a solid (0.035 g, 32%). LCMS (Method K): RT 2.76 min [M+H]+ 376.0. 1H NMR (MeOD-d4) δ: 8.33 (1H, br s), 8.05 (1H, br s), 7.53-7.61 (2H, m), 6.97-7.04 (1H, m), 6.02 (1H, br s), 5.76-5.87 (1H, m), 3.38-3.49 (2H, m), 3.21-3.30 (2H, m), 2.76-2.88 (1H, m), 2.37-2.47 (1H, m), 1.76 (3H, d, J=6.1 Hz)

Workup

  1. temperatureAfter cooling
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. washwas washed with DCM and MeOH
  4. washthe product eluted with 2M NH3/MeOH
  5. concentrationthen concentrated in vacuo
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with 100% DCM—10% methanol in DCM

Sources & evidence

ORD record
ord-7f4d02b561c1459bbdee7ead55889658
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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