Acetic Acid → 1-(1,3-Dimethyl-1H-pyrazol-4-yl)-8-(5-ethylamino-pyridin-3-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one

HRID 445681Notes

Reaction equation

HRID 445681 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:17]=[CH:16][C:15]3[N:14]=[CH:13][C:12]4[N:18]([CH3:29])[C:19](=[O:28])[N:20]([C:21]5[C:22]([CH3:27])=[N:23][N:24]([CH3:26])[CH:25]=5)[C:11]=4[C:10]=3[CH:9]=2)[CH:5]=[N:6][CH:7]=1.[CH:30](=O)[CH3:31].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH3:26][N:24]1[CH:25]=[C:21]([N:20]2[C:11]3[C:10]4[CH:9]=[C:8]([C:4]5[CH:5]=[N:6][CH:7]=[C:2]([NH:1][CH2:30][CH3:31])[CH:3]=5)[CH:17]=[CH:16][C:15]=4[N:14]=[CH:13][C:12]=3[N:18]([CH3:29])[C:19]2=[O:28])[C:22]([CH3:27])=[N:23]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 177AcetaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 596196138-(5-amino-pyridin-3-yl)-1-(1,3-dimethyl-1H-pyrazol-4-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one

Product 1

HCID 596198581-(1,3-Dimethyl-1H-pyrazol-4-yl)-8-(5-ethylamino-pyridin-3-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 8-(5-amino-pyridin-3-yl)-1-(1,3-dimethyl-1H-pyrazol-4-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one (Example 45, 38 mg, 0.099 mmol), acetaldehyde (Fluka, Buchs, Switzerland, 4.8 mg, 0.108 mmol) in DCM (2 ml) was stirred for 1.5 h at rt in presence of acetic acid (0.02 ml, 3.54 mmol). Was added sodium triacetoxyborohydride (52.2 mg, 0.246 mmol) and the RM was stirred 1.5 h at rt, before being quenched with aqueous saturated NaHCO3 and extracted with DCM (2×). The combined organic layers were dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by Prep.HPLC (H2O (0.1% TFA)/CH3CN 95:5 to 60:40). The fractions containing products were collected together and basified with NaHCO3 (0.3 g), before being concentrated, saturated with NaCl and extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered and evaporated to give the title compound as an off-white solid. (HPLC: tR 2.13 min (Method A); M+H=414 MS-ES; 1H-NMR (d6-DMSO, 400 MHz) 8.97 (s, 1H), 8.13-8.08 (m, 2H), 7.97-7.95 (m, 1H), 7.92-7.88 (m, 2H), 7.60-7.58 (m, 1H), 6.88-6.85 (m, 1H), 6.01 (t, 1H), 3.89 (s, 3H), 3.58 (s, 3H), 3.15-3.06 (m, 2H), 1.95 (s, 3H), 1.21 (t, 3H))

Workup

  1. custombefore being quenched with aqueous saturated NaHCO3
  2. extractionextracted with DCM (2×)
  3. dry with materialThe combined organic layers were dried over Na2SO4
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe residue was purified by Prep.HPLC (H2O (0.1% TFA)/CH3CN 95:5 to 60:40)
  7. additionThe fractions containing products
  8. customwere collected together
  9. concentrationbefore being concentrated, saturated with NaCl
  10. extractionextracted with EtOAc (3×)
  11. dry with materialThe combined organic layers were dried over Na2SO4
  12. filtrationfiltered
  13. customevaporated

Sources & evidence

ORD record
ord-414619453bdf4efca6f98098e180f5e9
Source dataset
uspto-grants-2013_07
Patent number
US08476294B2

Reaction notes

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