Tetrahydrofuran → (2S)-2-[{4-[(4-formylphenyl)ethynyl]benzoyl}(methyl)amino]-N,2-dimethyl-N'-(tetrahydro-2H-pyran-2-yloxy)propanediamide

HRID 1519703ノート

反応式

HRID 1519703 の反応式
I[C:2]1[CH:27]=[CH:26][C:5]([C:6]([N:8]([CH3:25])[C@:9]([CH3:24])([C:14]([NH:16][O:17][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)=[O:15])[C:10]([NH:12][CH3:13])=[O:11])=[O:7])=[CH:4][CH:3]=1.[C:28]([C:30]1[CH:37]=[CH:36][C:33]([CH:34]=[O:35])=[CH:32][CH:31]=1)#[CH:29].C1COCC1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.C(OCC)(=O)C>[CH:34]([C:33]1[CH:36]=[CH:37][C:30]([C:28]#[C:29][C:2]2[CH:27]=[CH:26][C:5]([C:6]([N:8]([CH3:25])[C@:9]([CH3:24])([C:14]([NH:16][O:17][CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][O:19]3)=[O:15])[C:10]([NH:12][CH3:13])=[O:11])=[O:7])=[CH:4][CH:3]=2)=[CH:31][CH:32]=1)=[O:35]

参加物

7

反応物 3

HCID 8028TetrahydrofuranHCID 27716454-EthynylbenzaldehydeHCID 86679252HCID 86679252、化合物2 回

生成物 1

HCID 86679270(2S)-2-[{4-[(4-formylphenyl)ethynyl]benzoyl}(methyl)amino]-N,2-dimethyl-N'-(tetrahydro-2H-pyran-2-yloxy)propanediamide収率 76%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418476HCID 178418476、化合物触媒HCID 8857Ethyl Acetate溶媒

実験手順

TEA (10 mL) was added dropwise to a mixture of (2S)-2-[(4-iodobenzoyl)(methyl)amino]-N,2-dimethyl-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (Intermediate 15, 12 g), 4-ethynylbenzaldehyde (4.1 g), PdCl2(PPh3)2 (0.85 g), CuI (0.46 g), and THF (60 mL) at room temperature in a nitrogen atmosphere, and the mixture was stirred for 2 hours and 15 minutes at room temperature. Ethyl acetate (0.20 L), OH type silica gel (12 g), cellpure (5.9 g) and activated carbon (0.60 g) were added, the insolubles were filtered out, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by OH type silica gel column chromatography (ethyl acetate/hexane=50/50, followed by gradient elution with chloroform/acetone=100/0→80/20). Then, ethyl acetate and IPE were added to the resulting solid, and the solid was filtered off and washed with IPE to obtain (2S)-2-[{4-[(4-formylphenyl)ethynyl]benzoyl}(methyl)amino]-N,2-dimethyl-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (yellow brown solid) (9.0 g, 76%).

後処理

  1. filtrationthe insolubles were filtered out
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customThe resulting residue was purified by OH type silica gel column chromatography (ethyl acetate/hexane=50/50, followed by gradient elution with chloroform/acetone=100/0→80/20)
  4. additionThen, ethyl acetate and IPE were added to the resulting solid
  5. filtrationthe solid was filtered off
  6. washwashed with IPE

出典と根拠

ORDレコード
ord-5ecd9a05351f4316887588155e505ae7
出典データセット
uspto-grants-2015_07
特許番号
US09073821B2

反応ノート

読み込み中…