Tetrahydrofuran → (2S)-2-[(4-{[5-(methoxymethyl)furan-3-yl]ethynyl}benzoyl)(methyl)amino]-N,2-dimethyl-N'-(tetrahydro-2H-pyran-2-yloxy)propanediamide

HRID 1519718ノート

反応式

HRID 1519718 の反応式
C1COCC1.[C:6]([C:8]1[CH:9]=[C:10]([CH2:13][O:14][CH3:15])[O:11][CH:12]=1)#[CH:7].I[C:17]1[CH:42]=[CH:41][C:20]([C:21]([N:23]([CH3:40])[C@:24]([CH3:39])([C:29]([NH:31][O:32][CH:33]2[CH2:38][CH2:37][CH2:36][CH2:35][O:34]2)=[O:30])[C:25]([NH:27][CH3:28])=[O:26])=[O:22])=[CH:19][CH:18]=1>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>[CH3:15][O:14][CH2:13][C:10]1[O:11][CH:12]=[C:8]([C:6]#[C:7][C:17]2[CH:42]=[CH:41][C:20]([C:21]([N:23]([CH3:40])[C@:24]([CH3:39])([C:29]([NH:31][O:32][CH:33]3[CH2:38][CH2:37][CH2:36][CH2:35][O:34]3)=[O:30])[C:25]([NH:27][CH3:28])=[O:26])=[O:22])=[CH:19][CH:18]=2)[CH:9]=1

参加物

7

反応物 3

HCID 8028TetrahydrofuranHCID 86679252HCID 86679252、化合物2 回HCID 866792824-Ethynyl-2-(methoxymethyl)furan

生成物 1

HCID 86679283(2S)-2-[(4-{[5-(methoxymethyl)furan-3-yl]ethynyl}benzoyl)(methyl)amino]-N,2-dimethyl-N'-(tetrahydro-2H-pyran-2-yloxy)propanediamide収率 84%

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

PdCl2(PPh3)2 (70 mg), CuI (38 mg) and TEA (1.5 mL) were added to a THF (7.0 mL) solution of 4-ethynyl-2-(methoxymethyl)furan (0.24 g) as obtained in Example 18-(3) and (2S)-2-[(4-iodobenzoyl)(methyl)amino]-N,2-dimethyl-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (Intermediate 15, 0.51 g), and the mixture was stirred for 5.5 hours at room temperature in a nitrogen atmosphere. Ethyl acetate (30 mL), OH type silica gel (1.9 g), cellpure (0.95 g) and activated carbon (50 mg) 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 (gradient elution with ethyl acetate/hexane=75/25→100/0, followed by gradient elution with chloroform/acetone=100/0→70/30) to obtain (2S)-2-[(4-{[5-(methoxymethyl)furan-3-yl]ethynyl}benzoyl)(methyl)amino]-N,2-dimethyl-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (yellow solid) (0.43 g, 84%).

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 (gradient elution with ethyl acetate/hexane=75/25→100/0, followed by gradient elution with chloroform/acetone=100/0→70/30)

出典と根拠

ORDレコード
ord-06cdd491e6b641c58d58f2082a162019
出典データセット
uspto-grants-2015_07
特許番号
US09073821B2

反応ノート

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