Acetic Acid → 6-Chloro-7-(2,3-dihydro-1H-indol-1-yl)-2-{4-[2-(4-morpholinyl)ethoxy]phenyl}-1H-imidazo[4,5-b]pyridine

HRID 2218389Notes

Reaction equation

HRID 2218389 reaction equation
[Cl:1][C:2]1[C:3](Cl)=[C:4]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][N:20]4[CH2:25][CH2:24][O:23][CH2:22][CH2:21]4)=[CH:13][CH:12]=3)[NH:8][C:5]2=[N:6][CH:7]=1.[NH:27]1[C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH2:29][CH2:28]1.O.C(O)(=O)C>C1(C)C(C)=CC=CC=1>[Cl:1][C:2]1[C:3]([N:27]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[CH2:29][CH2:28]2)=[C:4]2[NH:10][C:9]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][N:20]4[CH2:25][CH2:24][O:23][CH2:22][CH2:21]4)=[CH:13][CH:12]=3)=[N:8][C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 962WaterHCID 10328IndolineHCID 178478272HCID 178478272, compound

Product 1

HCID 692130806-Chloro-7-(2,3-dihydro-1H-indol-1-yl)-2-{4-[2-(4-morpholinyl)ethoxy]phenyl}-1H-imidazo[4,5-b]pyridineYield 85.7%

Reagents, catalysts & solvents 1

HCID 7237O-XyleneSolvent

Conditions

Temperature
180 °C

Procedure

6,7-Dichloro-2-[4-(2-morpholin-4-ylethoxy)phenyl]-3H-imidazo[4,5-b]pyridine (Example 206) (30 mg 76 μmol) and indoline (0.10 ml, 790 μmol) were mixed in xylene (mixture of isomers, 0.75 ml) and heated in a microwave oven at 180° C. for 20 min. When cool again, water (0.75 ml) and acetic acid (0.75 ml) were added to the mixture, causing separation of two phases. The aqueous phase was separated and subjected to semi-preparative HPLC-C18. The appropriate fractions were pooled and evaporated in vacuo. The yellow oily residue was dissolved in EtOAc (20 ml). This solution was washed with 1% aqueous NaHCO3 (20 ml) and brine (10 ml). The organic phase was dried (MgSO4) and evaporated in vacuo to afford the pure product (31 mg, 85%) as a pale yellow powder.

Workup

  1. temperatureWhen cool again
  2. customseparation of two phases
  3. customThe aqueous phase was separated
  4. customevaporated in vacuo
  5. dissolutionThe yellow oily residue was dissolved in EtOAc (20 ml)
  6. washThis solution was washed with 1% aqueous NaHCO3 (20 ml) and brine (10 ml)
  7. dry with materialThe organic phase was dried (MgSO4)
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-bf893aedb1344c21b2f514db937d9def
Source dataset
uspto-grants-2008_08
Patent number
US07410966B2

Reaction notes

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