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

HRID 1519718노트

반응식

HRID 1519718 반응식
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

참가 물질

7

반응물 3

HCID 8028TetrahydrofuranHCID 86679252HCID 86679252, 화합물2회HCID 866792824-Ethynyl-2-(methoxymethyl)furan

생성물 1

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

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418476HCID 178418476, 화합물촉매HCID 8857Ethyl Acetate용매

실험 절차

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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-06cdd491e6b641c58d58f2082a162019
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09073821B2

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