1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (E)-6-(3-Oxo-3-(3-(thiophen-2-ylmethoxy)azetidin-1-yl)prop-1-enyl)-1H-imidazo[4,5-b]pyridin-2(3H)-one

HRID 83033

Reaction equation

HRID 83033 reaction equation
Cl.[S:2]1[CH:6]=[CH:5][CH:4]=[C:3]1[CH2:7][O:8][CH:9]1[CH2:12][NH:11][CH2:10]1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.Cl.[O:44]=[C:45]1[NH:58][C:48]2=[N:49][CH:50]=[C:51](/[CH:53]=[CH:54]/[C:55](O)=[O:56])[CH:52]=[C:47]2[NH:46]1>CN(C)C=O>[O:56]=[C:55]([N:11]1[CH2:12][CH:9]([O:8][CH2:7][C:3]2[S:2][CH:6]=[CH:5][CH:4]=2)[CH2:10]1)/[CH:54]=[CH:53]/[C:51]1[CH:52]=[C:47]2[NH:46][C:45](=[O:44])[NH:58][C:48]2=[N:49][CH:50]=1

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 671545443-(2-Thienylmethoxy)azetidine hydrochlorideHCID 70926863(E)-3-(2-Oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-6-yl)acrylic acid hydrochloride

Product 1

HCID 52950704(E)-6-(3-Oxo-3-(3-(thiophen-2-ylmethoxy)azetidin-1-yl)prop-1-enyl)-1H-imidazo[4,5-b]pyridin-2(3H)-oneYield 14.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-(Thiophen-2-ylmethoxy)-azetidine hydrochloride (127 mg, 0.62 mmol), EDCI (120 mg, 0.62 mmol), HOBt (86 mg, 0.62 mmol) and diisopropylethylamine (180 μL, 1.03 mmol) were successively added to a solution of (E)-3-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-6-yl)acrylic acid hydrochloride (100 mg, 0.41 mmol) in dimethylformamide (10 mL) at room temperature. The reaction mixture was stirred overnight then partitioned between ethyl acetate (20 mL) and water (30 mL). The aqueous layer was separated and successively extracted with ethyl acetate (2×20 mL) and dichloromethane (2×20 mL). The combined organic phases were washed with a saturated solution of sodium chloride (3×30 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by chromatography on silica gel using dichloromethane/methanol (98:2 to 93:7) as eluent. The residue was triturated in pentane to afford the title product as a pale orange solid (21 mg, 14%).

Workup

  1. customthen partitioned between ethyl acetate (20 mL) and water (30 mL)
  2. customThe aqueous layer was separated
  3. extractionsuccessively extracted with ethyl acetate (2×20 mL) and dichloromethane (2×20 mL)
  4. washThe combined organic phases were washed with a saturated solution of sodium chloride (3×30 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe residue was purified by chromatography on silica gel
  9. customThe residue was triturated in pentane

Sources & evidence

ORD record
ord-e804a1ab53e341f5bfef05a2426c4de4
Source dataset
uspto-grants-2014_09
Patent number
US08846711B2

Linked notes

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