Diisopropylethylamine → HCID 178461959, compound

HRID 243291Notes

Reaction equation

HRID 243291 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]([C@@H:11]([NH2:13])[CH3:12])[N:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1.Cl[C:21]1[N:29]=[CH:28][N:27]=[C:26]2[C:22]=1[N:23]=[CH:24][NH:25]2.CCN(C(C)C)C(C)C>C(O)CCC>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]([C@@H:11]([NH:13][C:21]3[N:29]=[CH:28][N:27]=[C:26]4[C:22]=3[N:23]=[CH:24][NH:25]4)[CH3:12])[N:7]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 81531Diisopropylethylamine2×HCID 68158216(S)-1-(4-Chloro-1-phenyl-1H-benzo[D]imidazol-2-YL)ethanamineHCID 178478393HCID 178478393, compound2×

Product 1

HCID 178461959HCID 178461959, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of (S)-1-(4-chloro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine from Example 9 (250 mg, 0.92 mmol), 6-chloro-9H-purine (200 mg, 1.29 mmol) and DIPEA (0.29 mL, 1.66 mmol) in n-butanol (2 mL) was stirred in a sealed tube for 16 h at 120° C. Additional amounts of 6-chloro-9H-purine (100 mg, 0.64 mmol) and DIPEA (0.14 mL, 0.802 mmol) were added and the stirring was continued at 120° C. for 24 h. After cooling to RT, the crude reaction mixture was partitioned between DCM and water. The aqueous phase was further extracted with DCM (×3) and then the combined organic layers were washed with brine, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-8% 2M NH3/MeOH in DCM) and then by preparative HPLC (Phenomenex Gemini 5 μm C18 on a 60 min gradient 20-98% 0.1% HCO2H in acetonitrile/water) affording 120 (66 mg, 42%). LCMS: RT 3.69 min [M+H]+ 390.0. 1H NMR (CDCl3, 400 MHz): δ 12.90 (1H, bs), 8.28-7.90 (3H, m), 7.71-7.41 (5H, m), 7.32 (1H, d, J=7.75 Hz), 7.19 (1H, t, J=7.90 Hz), 7.03 (1H, d, J=8.10 Hz), 5.46 (1H, br), 1.67-1.53 (3H, m)

Workup

  1. waitthe stirring was continued at 120° C. for 24 h
  2. temperatureAfter cooling to RT
  3. customthe crude reaction mixture
  4. customwas partitioned between DCM and water
  5. extractionThe aqueous phase was further extracted with DCM (×3)
  6. washthe combined organic layers were washed with brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-8% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-4f4b0e6bb0a74c3bbfc7718ba3d8f387
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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