Diisopropylethylamine → HCID 178461920, compound

HRID 243293Notes

Reaction equation

HRID 243293 reaction equation
[NH2:1][C@H:2]([C:4]1[N:5]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:6]2[CH:12]=[C:11]([C:13]#[N:14])[CH:10]=[CH:9][C:7]=2[N:8]=1)[CH3:3].Cl[C:22]1[N:30]=[CH:29][N:28]=[C:27]2[C:23]=1[N:24]=[CH:25][NH:26]2.CCN(C(C)C)C(C)C>C(O)CCC>[N:30]1[C:22]([NH:1][C@H:2]([C:4]2[N:5]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:6]3[CH:12]=[C:11]([C:13]#[N:14])[CH:10]=[CH:9][C:7]=3[N:8]=2)[CH3:3])=[C:23]2[C:27]([NH:26][CH:25]=[N:24]2)=[N:28][CH:29]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 68157742(S)-2-(1-Aminoethyl)-1-phenyl-1H-benzo[D]imidazole-6-carbonitrileHCID 178478393HCID 178478393, compound

Product 1

HCID 178461920HCID 178461920, compoundYield 37.6%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 2-((S)-1-aminoethyl)-3-phenyl-3H-benzoimidazole-5-carbonitrile from Example 11 (370 mg, 1.4 mmol), 6-chloro-9H-purine (217 mg, 1.4 mmol) and DIPEA (0.36 mL, 2.1 mmol) in n-butanol (2.8 mL) was stirred in a sealed tube for 6 h at 120° C. After cooling to RT, the crude reaction mixture was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 2M NH3/MeOH. The product containing fractions were combined and concentrated under reduced pressure. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in EtOAc followed by gradient 0-10% 2M NH3/MeOH in DCM) affording 122 as a white solid (200 mg, 37%). LCMS: RT 3.29 min [M+H]+ 381.1. 1H NMR (DMSO, 400 MHz): δ 8.21-7.97 (3H, m), 7.84 (1H, d, J=8.35 Hz), 7.72-7.46 (7H, m), 5.49 (1H, br), 1.59 (3H, d, J=6.87 Hz)

Workup

  1. temperatureAfter cooling to RT
  2. customthe crude reaction mixture
  3. washwas washed with MeOH
  4. washthe product eluted with 2M NH3/MeOH
  5. additionThe product containing fractions
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in EtOAc followed by gradient 0-10% 2M NH3/MeOH in DCM)

Sources & evidence

ORD record
ord-962181514d64463baac502f11dfa24ff
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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