1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (E)-4-(4-Methoxybenzyl)-7-(3-oxo-3-(3-(thiophen-2-ylmethoxy)azetidin-1-yl)prop-1-enyl)-4,5-dihydro-1H-pyrido[2,3-e][1,4]diazepin-2(3H)-one

HRID 83013

Reaction equation

HRID 83013 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][O:45][C:46]1[CH:69]=[CH:68][C:49]([CH2:50][N:51]2[CH2:57][C:56]3[CH:58]=[C:59](/[CH:62]=[CH:63]/[C:64](O)=[O:65])[CH:60]=[N:61][C:55]=3[NH:54][C:53](=[O:67])[CH2:52]2)=[CH:48][CH:47]=1>CN(C)C=O.O.C(OCC)(=O)C>[CH3:44][O:45][C:46]1[CH:69]=[CH:68][C:49]([CH2:50][N:51]2[CH2:57][C:56]3[CH:58]=[C:59](/[CH:62]=[CH:63]/[C:64](=[O:65])[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:60]=[N:61][C:55]=3[NH:54][C:53](=[O:67])[CH2:52]2)=[CH:48][CH:47]=1

Participants

9

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 66966837HCID 66966837, compoundHCID 671545443-(2-Thienylmethoxy)azetidine hydrochloride

Product 1

HCID 68307379(E)-4-(4-Methoxybenzyl)-7-(3-oxo-3-(3-(thiophen-2-ylmethoxy)azetidin-1-yl)prop-1-enyl)-4,5-dihydro-1H-pyrido[2,3-e][1,4]diazepin-2(3H)-oneYield 40%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-(Thiophen-2-ylmethoxy)-azetidine hydrochloride (231 mg, 1.12 mmol), EDCI (215 mg, 1.12 mmol), HOBt (152 mg, 1.12 mmol) and diisopropylethylamine (321 μL, 1.87 mmol) were successively added to a solution of (E)-3-(4-(4-methoxybenzyl)-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)acrylic acid hydrochloride (292 mg, 0.75 mmol) in dimethylformamide (20 mL) at room temperature. The reaction mixture was stirred overnight and then diluted by addition of ethyl acetate (30 ml) and water (30 mL). The aqueous layer was separated and extracted with ethyl acetate (2×30 mL) and dichloromethane (2×20 mL). The combined organic phases were washed with a saturated solution of sodium chloride (3×20 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was precipitated from a mixture ethyl acetate/diethyl ether to afford the title product as an off-white solid (151 mg, 40%).

Workup

  1. customThe aqueous layer was separated
  2. extractionextracted with ethyl acetate (2×30 mL) and dichloromethane (2×20 mL)
  3. washThe combined organic phases were washed with a saturated solution of sodium chloride (3×20 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customThe residue was precipitated from a mixture ethyl acetate/diethyl ether

Sources & evidence

ORD record
ord-a5cfe639891244d0ac9900216e8a9bd5
Source dataset
uspto-grants-2014_09
Patent number
US08846711B2

Linked notes

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