7-Aminobenzimidazole → 1-(1H-benzimidazol-4-yl)-5-(benzyloxy)-2-methylpyridin-4(1H)-one

HRID 571065Notes

Reaction equation

HRID 571065 reaction equation
[CH2:1]([O:8][C:9]1[C:10](=[O:16])[CH:11]=[C:12]([CH3:15])O[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:17]1[C:21]2[CH:22]=[CH:23][CH:24]=[C:25]([NH2:26])[C:20]=2[N:19]=[CH:18]1>CC(O)=O.O>[NH:17]1[C:21]2[CH:22]=[CH:23][CH:24]=[C:25]([N:26]3[CH:14]=[C:9]([O:8][CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)[C:10](=[O:16])[CH:11]=[C:12]3[CH3:15])[C:20]=2[N:19]=[CH:18]1

Participants

4

Reactant 2

HCID 203297-AminobenzimidazoleHCID 53141715-(Benzyloxy)-2-methyl-4H-pyran-4-one

Product 1

HCID 674417131-(1H-benzimidazol-4-yl)-5-(benzyloxy)-2-methylpyridin-4(1H)-one

Reagents, catalysts & solvents 1

HCID 21899381Acetic acid--water (1/1)Solvent

Conditions

Temperature
140 °C

Procedure

5-(Benzyloxy)-2-methyl-4H-pyran-4-one (450 mg, 2.081 mmol) and 1H-benzimidazol-4-amine (279 mg, 2.095 mmol) were taken up in 40% HOAc/H2O (10 ml) in a microwave vial. The vial was sealed and the mixture heated to 140° C. for 30 min by microwave irradiation. The reaction was incomplete by LC/MS. The mixture was heated to 200° C. for 30 min by microwave irradiation. The reaction was incomplete by LC/MS. The mixture was heated to 170° C. for 1 h by microwave irradiation. The mixture was concentrated. The crude material was purified by preparative reversed-phase HPLC (30×150 mm Waters Sunfire (0.1% TFA), 5-35% ACN/water over 20 min at 50 mL/min, 2 injections). Fractions containing each compound were pooled separately then applied to separate Phenomenex Strata-X—C ion exchange columns (5 g). Each column was washed with H2O and MeOH (discard) then with 10% concentrated NH4OH in MeOH (collect). The collected fractions for each were concentrated separately to give the title compounds below: 1-(1H-benzimidazol-4-yl)-5-(benzyloxy)-2-methylpyridin-4(1H)-one: tan solid LC/MS rt=1.24 min, 1H NMR (500 MHz, d6-DMSO) δ 12.90 (bs, 1 H), 8.33 (s, 1 H), 7.72 (bs, 1 H), 7.49 (bs, 1 H), 7.41-7.25 (m, 7 H), 6.26 (s, 1 H), 4.94 (s, 2 H), 1.92 (s, 3 H). 1-(1H-benzimidazol-4-yl)-5-hydroxy-2-methylpyridin-4(1H)-one: tan solid, LC/MS rt=0.47 min, 1H NMR (500 MHz, d6-DMSO) δ 12.88 (bs, 1 H), 8.32 (s, 1 H), 7.70 (d, J=8.06 Hz, 1 H), 7.38-7.25 (m, 3 H), 6.25 (s, 1 H), 1.92 (s, 3 H).

Workup

  1. customThe vial was sealed
  2. temperatureThe mixture was heated to 200° C. for 30 min by microwave irradiation
  3. temperatureThe mixture was heated to 170° C. for 1 h by microwave irradiation
  4. concentrationThe mixture was concentrated
  5. customThe crude material was purified by preparative reversed-phase HPLC (30×150 mm Waters Sunfire (0.1% TFA), 5-35% ACN/water over 20 min at 50 mL/min, 2 injections)
  6. additionFractions containing each compound
  7. customto separate Phenomenex Strata-X—C ion exchange columns (5 g)
  8. washEach column was washed with H2O and MeOH (discard)
  9. concentrationThe collected fractions for each were concentrated separately

Sources & evidence

ORD record
ord-d55ea34650eb49578bcf0fb6b3ef33be
Source dataset
uspto-grants-2015_05
Patent number
US09024032B2

Reaction notes

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