Acetone → HCID 178456260, compound

HRID 243301Notes

Reaction equation

HRID 243301 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[C@@H:16]([NH:18][C:19]2[N:27]=[CH:26][N:25]=[C:24]3[C:20]=2[N:21]=[CH:22][NH:23]3)[CH3:17])[CH2:3][CH2:2]1.[CH3:28][C:29]([CH3:31])=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.CC(O)=O>[CH:29]([N:1]1[CH2:6][CH2:5][CH:4]([N:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[N:9]=[C:8]2[C@@H:16]([NH:18][C:19]2[N:27]=[CH:26][N:25]=[C:24]3[C:20]=2[N:21]=[CH:22][NH:23]3)[CH3:17])[CH2:3][CH2:2]1)([CH3:31])[CH3:28]

Participants

6

Reactant 3

HCID 180AcetoneHCID 5049666Sodium triacetoxyborohydrideHCID 178461903HCID 178461903, compound

Product 1

HCID 178456260HCID 178456260, compoundYield 24.4%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 6344DichloromethaneSolvent

Procedure

To a mixture of (S)—N-(1-(1-(piperidin-4-yl)-1H-benzo[d]imidazol-2-yl)ethyl)-9H-Aurin-6-amine from Example 113 (81 mg, 0.223 mmol) in anhydrous DCM (2 mL) was added acetone (49 μL, 0.67 mmol) followed by AcOH (1 drop). After stirring for 5 min, sodium triacetoxyborohydride (71 mg, 0.335 mmol) was added and stirring was continued for 19 h. The crude reaction mixture was loaded into an Isolute® SCX-2 which was washed with MeOH and the product eluted with 2M NH3/MeOH. The product containing fractions were combined and concentrated in vacuo and the resulting residue was purified by preparative HPLC (Phenomenex Gemini 5 μm C18 on a 20 min gradient 5-40% 0.1% NH4OH in acetonitrile/water) followed by Isolute® SCX-2 purification. The cartridge was washed with MeOH and the product eluted with 2M NH3/MeOH. The product containing fractions were combined and concentrated in vacuo affording 131 as a pale yellow solid (22 mg, 24%). LCMS: RT 1.68 min [M+H]+ 405.1. 1H NMR (DMSO plus TFA, 400 MHz): δ 8.82 (1H, bs), 8.57 (1H, s), 8.22 (1H, d, J=8.16 Hz), 7.77 (1H, d, J=7.78 Hz), 7.64-7.52 (2H, m), 5.97 (1H, bs), 5.49-5.35 (1H, br), 3.79-3.58 (3H, m), 3.43-3.24 (2H, m), 3.00-2.78 (2H, m), 2.68-2.48 (3H, m), 2.38 (1H, bd, J=16.58 Hz), 1.89 (3H, d, J=6.93 Hz), 1.36 (6H, dd, J=6.61, 2.47 Hz)

Workup

  1. stirringstirring
  2. waitwas continued for 19 h
  3. customThe crude reaction mixture
  4. washwas washed with MeOH
  5. washthe product eluted with 2M NH3/MeOH
  6. additionThe product containing fractions
  7. concentrationconcentrated in vacuo
  8. customthe resulting residue was purified by preparative HPLC (Phenomenex Gemini 5 μm C18 on a 20 min gradient 5-40% 0.1% NH4OH in acetonitrile/water)
  9. customfollowed by Isolute® SCX-2 purification
  10. washThe cartridge was washed with MeOH
  11. washthe product eluted with 2M NH3/MeOH
  12. additionThe product containing fractions
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d0fca579b89b4eeeb4ca93a7f550f5d6
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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