1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (E)-3-(3-((Dimethylamino)methyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-1-(3-(thiophen-2-ylmethoxy)azetidin-1-yl)prop-2-en-1-one

HRID 2172085Notes

Reaction equation

HRID 2172085 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.[CH3:44][N:45]([CH2:47][C:48]1[C:56]2[C:51](=[N:52][CH:53]=[C:54](/[CH:57]=[CH:58]/[C:59](O)=[O:60])[CH:55]=2)[NH:50][CH:49]=1)[CH3:46]>CN(C)C=O>[CH3:44][N:45]([CH2:47][C:48]1[C:56]2[C:51](=[N:52][CH:53]=[C:54](/[CH:57]=[CH:58]/[C:59]([N:11]3[CH2:12][CH:9]([O:8][CH2:7][C:3]4[S:2][CH:6]=[CH:5][CH:4]=4)[CH2:10]3)=[O:60])[CH:55]=2)[NH:50][CH:49]=1)[CH3:46]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 671545443-(2-Thienylmethoxy)azetidine hydrochlorideHCID 70926878(E)-3-(3-((Dimethylamino)methyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)acrylic acid hydrochloride

Product 1

HCID 52950703(E)-3-(3-((Dimethylamino)methyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-1-(3-(thiophen-2-ylmethoxy)azetidin-1-yl)prop-2-en-1-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-(Thiophen-2-ylmethoxy)-azetidine hydrochloride (61 mg, 0.30 mmol), EDCI (71.5 mg, 0.37 mmol), HOBt (52 mg, 0.37 mmol) and diisopropylethylamine (110 μL, 0.62 mmol) were successively added to a solution of (E)-3-(3-((dimethylamino)methyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)acrylic acid hydrochloride (70 mg, 0.25 mmol) in dimethylformamide (10 mL) at room temperature. The reaction mixture was stirred overnight then partitioned between ethyl acetate (30 mL) and water (30 mL). The aqueous layer was separated, gasified with an aqueous solution of sodium hydroxyde (2N) until pH 12 and finally extracted with ethyl acetate (2×50 mL). The combined organic phases were washed with a saturated solution of sodium chloride (3×50 mL), dried over sodium sulfate and concentrated to dryness. The residue was purified by chromatography on silica gel using dichloromethane/methanol/ammoniac (1:0:0.1 to 9:1:0.1) as eluent. The title product was obtained as a yellow solid (10 mg, 10%).

Workup

  1. customthen partitioned between ethyl acetate (30 mL) and water (30 mL)
  2. customThe aqueous layer was separated
  3. extractionfinally extracted with ethyl acetate (2×50 mL)
  4. washThe combined organic phases were washed with a saturated solution of sodium chloride (3×50 mL)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated to dryness
  7. customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-3952edab58044f30973cf99ebecd9c3f
Source dataset
uspto-grants-2015_06
Patent number
US09051321B2

Reaction notes

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