Ethyl Acetate → Tert-butyl {-[({4-[4-(3-chlorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)carbonyl]benzyl}carbamate

HRID 386817ノート

反応式

HRID 386817 の反応式
[NH2:1][C:2]1[C:3]([C:7]2[N:11]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[CH:13]=3)[C:10](=[O:19])[O:9][N:8]=2)=[N:4][O:5][N:6]=1.[C:20]([O:24][C:25]([NH:27][CH2:28][C:29]1[CH:37]=[CH:36][C:32](C(O)=O)=[CH:31][CH:30]=1)=[O:26])([CH3:23])([CH3:22])[CH3:21].C(N(CC)C(C)C)(C)C.[C:47](OCC)(=[O:49])C>ClCCl.CN(C)C1C=CN=CC=1>[Cl:18][C:14]1[CH:13]=[C:12]([N:11]2[C:10](=[O:19])[O:9][N:8]=[C:7]2[C:3]2[C:2]([NH:1][C:47]([CH:28]([NH:27][C:25](=[O:26])[O:24][C:20]([CH3:21])([CH3:22])[CH3:23])[C:29]3[CH:30]=[CH:31][CH:32]=[CH:36][CH:37]=3)=[O:49])=[N:6][O:5][N:4]=2)[CH:17]=[CH:16][CH:15]=1

参加物

7

反応物 4

HCID 8857Ethyl AcetateHCID 81531Diisopropylethylamine2 回HCID 8536054-(((tert-Butoxycarbonyl)amino)methyl)benzoic acidHCID 585582673-(4-amino-1,2,5-oxadiazol-3-yl)-4-(3-chlorophenyl)-1,2,4-oxadiazol-5(4H)-one

生成物 1

HCID 86660342Tert-butyl {-[({4-[4-(3-chlorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)carbonyl]benzyl}carbamate

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒

実験手順

A solution of 3-(4-amino-1,2,5-oxadiazol-3-yl)-4-(3-chlorophenyl)-1,2,4-oxadiazol-5(4H)-one (0.5 g, 1.8 mmol) and 4-{[(tert-butoxycarbonyl)amino]methyl}benzoic acid (0.67 g, 2.7 mmol) in dichloromethane (35 mL) was treated with 4-dimethylaminopyridine (0.13 g, 1.1 mmol) and N,N-diisopropylethylamine (0.93 mL, 5.4 mmol) followed by bromotris(pyrrolydino)phosphonium hexafluorophosphate (1.3 g, 2.7 mmol) and additional N,N-diisopropylethylamine (0.93 mL, 5.4 mmol). The reaction mixture was stirred for 16 h, diluted with ethyl acetate (˜200 mL) and washed with 0.1 M HCl (2×100 mL) and brine (25 mL), dried with sodium sulfate, filtered, and concentrated. Purification of the crude reaction mixture on silica gel gave the intermediate tert-butyl {-[({4-[4-(3-chlorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)carbonyl]benzyl}carbamate. This material was diluted with dichloromethane (30 mL), treated with 4.0 M HCl in 1,4-dioxane (4.5 mL), and stirred for 1 h. The reaction mixture was concentrated and purified by preparative LCMS to give the desired product (542 mg, 58%). LCMS for C18H14ClN6O4 (M+H)+: m/z=413.0.

後処理

  1. washwashed with 0.1 M HCl (2×100 mL) and brine (25 mL)
  2. dry with materialdried with sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification of the crude
  6. customreaction mixture on silica gel

出典と根拠

ORDレコード
ord-518b251591864f1da0c7f6a00616e579
出典データセット
uspto-grants-2013_02
特許番号
US08372870B2

反応ノート

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