Acetic Acid → HCID 22181296, compound

HRID 1796528Notes

Reaction equation

HRID 1796528 reaction equation
[CH:1]1([CH2:4][N:5]2[C:9]3=[N:10][CH:11]=[C:12]([NH:14][CH3:15])[CH:13]=[C:8]3[N:7]=[C:6]2[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH3:25])=[CH:19][CH:18]=2)[CH2:3][CH2:2]1.C(N(CC)CC)C.[S:33]1[CH:37]=[CH:36][CH:35]=[C:34]1[S:38](Cl)(=[O:40])=[O:39].CC(O)=O>C(#N)C>[CH:1]1([CH2:4][N:5]2[C:9]3=[N:10][CH:11]=[C:12]([N:14]([CH3:15])[S:38]([C:34]4[S:33][CH:37]=[CH:36][CH:35]=4)(=[O:40])=[O:39])[CH:13]=[C:8]3[N:7]=[C:6]2[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH3:25])=[CH:19][CH:18]=2)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8471TriethylamineHCID 855182-Thiophenesulfonyl chlorideHCID 22181289HCID 22181289, compound

Product 1

HCID 22181296HCID 22181296, compoundYield 18%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 3-(cyclopropylmethyl)-2-[(4-ethoxyphenyl)methyl]-N-methyl-3H-imidazo[4,5-b]pyridin-6-amine (250.0 mg, 0.74 mmol) in acetonitrile (5 mL) at room temperature was added triethylamine (207 mL, 1.49 mmol) followed by 2-thiophenesulfonyl chloride (176 μL, 0.96 mmol). The mixture was stirred overnight. The reaction mixture was concentrated in vacuo. The residue was dissolved into EtOAc (10 ml) and Na2CO3 saturated aqueous solution (10 mL). The phases were separated and the aqueous phase was back-extracted with additional EtOAc (10 mL). The organic phases were combined, dried with MgSO4, filtered and concentrated in vacuo. The residue was purified using preparative HPLC (C-18 column, 20 to 80% [0.1% AcOH in AcCN solution] in 0.1% AcOH aqueous solution) to provide 72 mg of the AcOH salt of the title compound N-[3-(cyclopropylmethyl)-2-[(4-ethoxyphenyl)methyl]-3H-imidazo[4,5-b]pyridin-6-yl]-N-methyl-2-thiophenesulfonamide (18% yield from 3-(cyclopropylmethyl)-2-[(4-ethoxyphenyl)methyl]-N-methyl-3H-imidazo[4,5-b]pyridin-6-amine). 1H-NMR (400 MHz, d3-MeOD): δ 0.37 (m, 2H), 0.43 (m, 2H), 1.10 (m, 1H), 1.35 (t, J=7.0 Hz, 3H), 3.32 (s, 3H), 3.99 (t, J=7.0 Hz, 2H), 4.10 (d, J=7.2 Hz, 2H), 4.32 (s, 2H), 6.86 (d, J=8.8 Hz, 2H), 7.17 (d, J=8.8 Hz, 2H), 7.20 (m, 1H), 7.44 (d, J=5.3 Hz, 1H), 7.61 (d, J=2.3 Hz, 1H), 7.85 (d, J=5.1 Hz, 1H), 8.15 (d, J=2.3 Hz, 1H). MS (ESI) (M+H)+: 483.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutionThe residue was dissolved into EtOAc (10 ml) and Na2CO3 saturated aqueous solution (10 mL)
  3. customThe phases were separated
  4. extractionthe aqueous phase was back-extracted with additional EtOAc (10 mL)
  5. dry with materialdried with MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified

Sources & evidence

ORD record
ord-d550d7c1aecb4932b7c46c03f6ca296f
Source dataset
uspto-grants-2006_04
Patent number
US07030139B2

Reaction notes

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