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

反応式

HRID 83013 の反応式
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

参加物

9

反応物 5

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

生成物 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)-one収率 40%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-a5cfe639891244d0ac9900216e8a9bd5
出典データセット
uspto-grants-2014_09
特許番号
US08846711B2

関連ノート

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