Ethyl orthoformate → 5-(4-{[4-(2-Methyl-1H-benzimidazol-1-yl)piperidin-1-yl]methyl}phenyl)-6-phenyl-1H-imidazo[4,5-b]pyridine

HRID 1869282Notes

Reaction equation

HRID 1869282 reaction equation
[CH3:1][C:2]1[N:6]([CH:7]2[CH2:12][CH2:11][N:10]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([C:20]4[N:25]=[C:24]([NH2:26])[C:23]([NH2:27])=[CH:22][C:21]=4[C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)=[CH:16][CH:15]=3)[CH2:9][CH2:8]2)[C:5]2[CH:34]=[CH:35][CH:36]=[CH:37][C:4]=2[N:3]=1.[CH2:38](OC(OCC)OCC)C>>[CH3:1][C:2]1[N:6]([CH:7]2[CH2:8][CH2:9][N:10]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([C:20]4[N:25]=[C:24]5[N:26]=[CH:38][NH:27][C:23]5=[CH:22][C:21]=4[C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)=[CH:16][CH:15]=3)[CH2:11][CH2:12]2)[C:5]2[CH:34]=[CH:35][CH:36]=[CH:37][C:4]=2[N:3]=1

Participants

3

Reactant 2

HCID 31214Ethyl orthoformateHCID 579860706-(4-{[4-(2-methyl-1H-benzimidazol-1-yl)piperidin-1-yl]methyl}phenyl)-5-phenylpyridine-2,3-diamine

Product 1

HCID 113525075-(4-{[4-(2-Methyl-1H-benzimidazol-1-yl)piperidin-1-yl]methyl}phenyl)-6-phenyl-1H-imidazo[4,5-b]pyridine

Procedure

6-(4-{[4-(2-Methyl-1H-benzimidazol-1-yl)piperidin-1-yl]methyl}phenyl)-5-phenylpyridine-2,3-diamine (4-4, 0.055 g, 0.11 mmol) was heated at reflux in triethylorthoformate. After 3 h the reaction was concentrated and stirred in 1M HCl for 1 h. The solution pH was adjusted to 7 with saturated aqueous Na2CO3. The mixture was extracted 3× with DCM. The residue was purified by flash column chromatography (elute with a gradient of 95:5 DCM/MeOH to 90:10). The resulting impure product was dissolved in 2 ml of formic acid and the resulting solution was heated to reflux for 2 h. The reaction was concentrated, diluted with saturated aqueous NaHCO3, and extracted 3× with DCM. The extracts were dried over Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography (elute with a gradient of 95:5 DCM MeOH to 90:10) to afford 5-(4-{[4-(2-Methyl-1H-benzimidazol-1-yl)piperidin-1-yl]methyl}phenyl)-6-phenyl-1H-imidazo[4,5-b]pyridine (6-1). 1H NMR (CDCl3) δ 8.20 (s, 1H), 7.93 (s, 1H), 7.42 (d, 2H, J=11.0 Hz), 7.37 (d, 2H, J=10.8 Hz), 7.37-7.21 (m, 6H), 4.20 (m, 1H), 3.65 (s, 2H), 3.14 (m, 2H), 2.65 (s overlapping with m, 5H), 2.23 (m, 2H), 1.80 (m, 2H). MS m/z (M+H)=499.16.

Workup

  1. concentrationAfter 3 h the reaction was concentrated
  2. extractionThe mixture was extracted 3× with DCM
  3. customThe residue was purified by flash column chromatography (
  4. washelute with a gradient of 95:5 DCM/MeOH to 90:10)
  5. dissolutionThe resulting impure product was dissolved in 2 ml of formic acid
  6. temperaturethe resulting solution was heated
  7. temperatureto reflux for 2 h
  8. concentrationThe reaction was concentrated
  9. additiondiluted with saturated aqueous NaHCO3
  10. extractionextracted 3× with DCM
  11. dry with materialThe extracts were dried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe residue was purified by flash column chromatography (
  15. washelute with a gradient of 95:5 DCM MeOH to 90:10)

Sources & evidence

ORD record
ord-142816a01f554f5bafcc4cf1d0cfbe07
Source dataset
uspto-grants-2009_12
Patent number
US07638530B2

Reaction notes

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