Triphenylphosphine → 3-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyloxy)-5-isopropyl-4-{[4-(3-{N-(2-nitrobenzenesulfonyl)-N-[1-carbamoyl-1-(methyl)ethyl]amino}propoxy)-2-methylphenyl]-methyl}-1H-pyrazole

HRID 2189370노트

반응식

HRID 2189370 반응식
[C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][C@H:6]1[O:24][C:25]1[C:29]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH2:39][CH2:40]O)=[CH:33][C:32]=2[CH3:42])=[C:28]([CH:43]([CH3:45])[CH3:44])[NH:27][N:26]=1)(=[O:3])[CH3:2].[CH3:46][C:47]([NH:52][S:53]([C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][C:57]=1[N+:62]([O-:64])=[O:63])(=[O:55])=[O:54])([CH3:51])[C:48]([NH2:50])=[O:49].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][C@H:6]1[O:24][C:25]1[C:29]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH2:39][CH2:40][N:52]([S:53]([C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][C:57]=3[N+:62]([O-:64])=[O:63])(=[O:55])=[O:54])[C:47]([C:48](=[O:49])[NH2:50])([CH3:46])[CH3:51])=[CH:33][C:32]=2[CH3:42])=[C:28]([CH:43]([CH3:44])[CH3:45])[NH:27][N:26]=1)(=[O:3])[CH3:2]

참가 물질

6

반응물 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 230788742-Methyl-2-(2-nitrobenzenesulfonylamino)propionamideHCID 689406463-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyloxy)-4-{[4-(3-hydroxypropoxy)-2-methylphenyl]-methyl}-5-isopropyl-1H-pyrazole

생성물 1

HCID 866332283-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyloxy)-5-isopropyl-4-{[4-(3-{N-(2-nitrobenzenesulfonyl)-N-[1-carbamoyl-1-(methyl)ethyl]amino}propoxy)-2-methylphenyl]-methyl}-1H-pyrazole수율 89.9%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-4-{[4-(3-hydroxypropoxy)-2-methylphenyl]-methyl}-5-isopropyl-1H-pyrazole (0.25 g) in tetrahydrofuran (2 mL) were added 2-methyl-2-(2-nitrobenzenesulfonylamino)propionamide (0.14 g), triphenylphosphine (0.12 g) and diethyl azodicarboxylate (40% toluene solution, 0.26 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=1/4-dichloromethane/methanol=20/1) to give 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-5-isopropyl-4-{[4-(3-{N-(2-nitrobenzenesulfonyl)-N-[1-carbamoyl-1-(methyl)ethyl]amino}propoxy)-2-methylphenyl]-methyl}-1H-pyrazole (0.32 g). This material was dissolved in acetonitrile (3 mL). To the solution were added cesium carbonate (0.46 g) and thiophenol (0.038 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with water and brine successively, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=1/5-dichloromethane/methanol=15/1-10/1) to give 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-4-[(4-(3-[1-carbamoyl-1-(methyl)ethylamino]propoxy)-2-methylphenyl)methyl]-5-isopropyl-1H-pyrazole (20 mg). This material was dissolved in methanol (1 mL). To the solution was added sodium methoxide (28% methanol solution, 0.01 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and the residue was purified by solid phase extraction on ODS (washing solvent: distilled water, eluent: methanol) to give the title compound (11 mg).

후처리

  1. customThe reaction mixture was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=1/4-dichloromethane/methanol=20/1)

출처 및 근거

ORD 기록
ord-09d1beff9e284648bd22be96a44e7a91
출처 데이터셋
uspto-grants-2012_12
특허 번호
US08324176B2

반응 노트

불러오는 중…