1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (E)-3-(2-(4-Methylpiperazin-1-yl)ethyl)-6-(3-oxo-3-(3-(thiophen-2-ylmethoxy)azetidin-1-yl)prop-1-enyl)-3,4-dihydropyrido[2,3-d]pyrimidin-2(1H)-one

HRID 83026

Reaction equation

HRID 83026 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]1[CH2:50][CH2:49][N:48]([CH2:51][CH2:52][N:53]2[CH2:58][C:57]3[CH:59]=[C:60](/[CH:63]=[CH:64]/[C:65](O)=[O:66])[CH:61]=[N:62][C:56]=3[NH:55][C:54]2=[O:68])[CH2:47][CH2:46]1>CN(C)C=O.O.C(OCC)(=O)C>[CH3:44][N:45]1[CH2:50][CH2:49][N:48]([CH2:51][CH2:52][N:53]2[CH2:58][C:57]3[CH:59]=[C:60](/[CH:63]=[CH:64]/[C:65](=[O:66])[N:11]4[CH2:12][CH:9]([O:8][CH2:7][C:3]5[S:2][CH:6]=[CH:5][CH:4]=5)[CH2:10]4)[CH:61]=[N:62][C:56]=3[NH:55][C:54]2=[O:68])[CH2:47][CH2:46]1

Participants

9

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 671545443-(2-Thienylmethoxy)azetidine hydrochlorideHCID 70927051HCID 70927051, compound

Product 1

HCID 52950702(E)-3-(2-(4-Methylpiperazin-1-yl)ethyl)-6-(3-oxo-3-(3-(thiophen-2-ylmethoxy)azetidin-1-yl)prop-1-enyl)-3,4-dihydropyrido[2,3-d]pyrimidin-2(1H)-one

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-(Thiophen-2-ylmethoxy)-azetidine hydrochloride (38 mg, 0.18 mmol), EDCI (35 mg, 0.18 mmol), HOBt (26 mg, 0.18 mmol) and diisopropylethylamine (54 μL, 0.31 mmol) were successively added to a solution of (E)-3-(3-(2-(4-methylpiperazin-1-yl)ethyl)-2-oxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-6-yl)acrylic acid hydrochloride (54 mg, 0.12 mmol) in dimethylformamide (6 mL) at room temperature. The reaction mixture was stirred for 2 days and then diluted by addition of ethyl acetate (50 mL) and water (50 mL). The aqueous layer was separated and 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, filtered and concentrated to dryness. The residue was purified by chromatography on silica gel using dichloromethane/methano/ammoniac (1:0:0.1 to 9:1:0.1) as eluent. After several triturations of the compound in diethylether and pentane and a recristallisation from acetone, the title product was obtained as an off-white solid (2 mg, 3%).

Workup

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

Sources & evidence

ORD record
ord-7582a52ce4644589b277a29da24c0875
Source dataset
uspto-grants-2014_09
Patent number
US08846711B2

Linked notes

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