Triphenylphosphine → (3R*,5S*)-3-{Cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-carbamoyl}-5-[[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-(2-nitro-benzenesulfonyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1698369ノート

反応式

HRID 1698369 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]([NH:14][S:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[N+:24]([O-:26])=[O:25])(=[O:17])=[O:16])[CH2:11][C@@H:10]([C:27](=[O:47])[N:28]([CH:44]2[CH2:46][CH2:45]2)[CH2:29][C:30]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[N:32]([CH2:39][CH2:40][CH2:41][O:42][CH3:43])[CH:31]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O[CH2:49][CH2:50][N:51]1[C:59](=[O:60])[C:58]2[C:53](=[CH:54][CH:55]=[CH:56][CH:57]=2)[C:52]1=[O:61].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][C@@H:12]([N:14]([CH2:49][CH2:50][N:51]2[C:52](=[O:61])[C:53]3[C:58](=[CH:57][CH:56]=[CH:55][CH:54]=3)[C:59]2=[O:60])[S:15]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=2[N+:24]([O-:26])=[O:25])(=[O:17])=[O:16])[CH2:11][C@@H:10]([C:27](=[O:47])[N:28]([CH:44]2[CH2:46][CH2:45]2)[CH2:29][C:30]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[N:32]([CH2:39][CH2:40][CH2:41][O:42][CH3:43])[CH:31]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

参加物

6

反応物 4

HCID 11776TriphenylphosphineHCID 77499N-(2-Hydroxyethyl)phthalimideHCID 5462977Diethyl azodicarboxylateHCID 69070266(3R*,5S*)-3-{Cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-carbamoyl}-5-(2-nitro-benzenesulfonylamino)-piperidine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 69071084(3R*,5S*)-3-{Cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-carbamoyl}-5-[[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethyl]-(2-nitro-benzenesulfonyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
60 °C

実験手順

To a solution of (3R*,5S*)3-{Cyclopropyl-[1-(3-methoxy-propyl)-1H-indol-3-ylmethyl]-carbamoyl}-5-(2-nitro-benzenesulfonylamino)-piperidine-1-carboxylic acid tert-butyl ester (400 mg, 0.60 mmol), 2-(2-hydroxyethyl) isoindole-1,3-dione (171 mg, 0.9 mmol), and PPh3 (315 mg, 1.2 mmol) in THF is added DEAD (208 mg, 1.2 mmol) at room temperature, then the mixture is stirred at 60° C. After 13 h, the reaction mixture is quenched by H2O (20 mL) and extracted with EtOAc (50 mL). The organic phase is successively washed with 5% aqueous KHSO4, H2O, and brine, then dried over Na2SO4 and concentrated in reduced pressure. The residue is purified by silica gel column chromatography to afford the title compound as yellow amorphous material. MS: 843 [M+H]+; tR (HPLC, ACQUITY UPLC™ BEH C18 1.7 μm, 50×2.1 mm; 5% CH3CN+0.1% TFA/H2O+0.1% TFA for 0.5 min then 5-100% CH3CN+0.1% TFA/H2O+0.1% TFA for 5 min then 100% CH3CN+0.1% TFA for 1.5 min, flow 0.5 ml/min): 4.41 min.

後処理

  1. customthe reaction mixture is quenched by H2O (20 mL)
  2. extractionextracted with EtOAc (50 mL)
  3. washThe organic phase is successively washed with 5% aqueous KHSO4, H2O, and brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in reduced pressure
  6. customThe residue is purified by silica gel column chromatography

出典と根拠

ORDレコード
ord-a283bb612bf24fcc80196c2e83aea6f1
出典データセット
uspto-grants-2012_04
特許番号
US08163773B2

反応ノート

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