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 633980Notes

Reaction equation

HRID 633980 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 recrystallisation 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
  8. customAfter several triturations of the compound in diethylether and pentane and a recrystallisation from acetone

Sources & evidence

ORD record
ord-052e73fb9a8a4675974db24e46d6e46a
Source dataset
uspto-grants-2016_04
Patent number
US09321769B2

Reaction notes

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