Acetic Acid → 5-chloro-3-(3-methoxypropyl)-2-(piperidin-3-yl)-3H-imidazo[4,5-b]pyridine

HRID 1096621Notes

Reaction equation

HRID 1096621 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][CH2:11][O:12][CH3:13])[C:5]([NH:14][C:15]([C@@H:17]2[CH2:22][CH2:21][CH2:20][N:19](C(OC(C)(C)C)=O)[CH2:18]2)=O)=[CH:4][CH:3]=1.C(O)(=O)C>C1(C)C=CC=CC=1>[Cl:1][C:2]1[N:7]=[C:6]2[N:8]([CH2:9][CH2:10][CH2:11][O:12][CH3:13])[C:15]([CH:17]3[CH2:22][CH2:21][CH2:20][NH:19][CH2:18]3)=[N:14][C:5]2=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 176Acetic AcidHCID 86761531(R)-tert-butyl 3-(6-chloro-2-(3-methoxypropylamino)pyridin-3-ylcarbamoyl)piperidine-1-carboxylate

Product 1

HCID 867615305-chloro-3-(3-methoxypropyl)-2-(piperidin-3-yl)-3H-imidazo[4,5-b]pyridineYield 10%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

Compound 35B (crude material, 2.84 mmol max) prepared in Step 13 was added to a 50 trLL round-bottomed flask equipped for stirring under nitrogen. Glacial acetic acid (10 mL) was then added and the resultant solution was stirred at reflux under nitrogen for 16 hr. The reaction solution was concentrated in-vacuo to give a brownish oil. Toluene (30 mL) was added and the subsequent solution was concentrated in vacuo; this was repeated three times to remove any trace quantities of acetic acid affording the title compound as a brown oil. This oil was then purified by preparative LC/MS (5-50% CH3CN in H2O) to afford 5-chloro-3-(3-methoxypropyl)-2-(piperidin-3-yl)-3H-imidazo[4,5-b]pyridine (35C) as a tan oil. (088 mmol, 0.122 g, 10% yield over 3-steps). Subsequent analysis of a later derivative of this compound revealed that the chiral center had been epimerized during this reaction sequence. ESI-MS: m/z 309.4 (M+H)+.

Workup

  1. additionwas added to a 50 trLL round-bottomed flask
  2. customequipped
  3. temperatureat reflux under nitrogen for 16 hr
  4. concentrationThe reaction solution was concentrated in-vacuo
  5. customto give a brownish oil
  6. concentrationthe subsequent solution was concentrated in vacuo
  7. customto remove any trace quantities of acetic acid affording the title compound as a brown oil
  8. customThis oil was then purified by preparative LC/MS (5-50% CH3CN in H2O)

Sources & evidence

ORD record
ord-b692579abddf4a618b579027f192e23e
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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