Diisopropylethylamine → [3-(3-Amino-1,2,4-oxadiazol-5-yl)-5-(4-ethylphenyl)piperidin-1-yl](4-hydroxypiperidin-1-yl)methanone

HRID 661209ノート

反応式

HRID 661209 の反応式
[CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][N:13]([C:15]([N:17]3[CH2:22][CH2:21][CH:20]([OH:23])[CH2:19][CH2:18]3)=[O:16])[CH2:12][CH:11]([C:24](O)=[O:25])[CH2:10]2)=[CH:5][CH:4]=1)[CH3:2].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.O.S(O)(O)(=O)=O.O[NH:76][C:77]([NH2:79])=[NH:78].ONC(N)=N>CN(C=O)C>[NH2:79][C:77]1[N:78]=[C:24]([CH:11]2[CH2:10][CH:9]([C:6]3[CH:7]=[CH:8][C:3]([CH2:1][CH3:2])=[CH:4][CH:5]=3)[CH2:14][N:13]([C:15]([N:17]3[CH2:22][CH2:21][CH:20]([OH:23])[CH2:19][CH2:18]3)=[O:16])[CH2:12]2)[O:25][N:76]=1

参加物

6

反応物 4

HCID 81531Diisopropylethylamine2 回HCID 2724699PyBOPHCID 580026415-(4-Ethylphenyl)-1-[(4-hydroxypiperidin-1-yl)carbonyl]piperidine-3-carboxylic acidHCID 178513195HCID 178513195、化合物

生成物 1

HCID 58116513[3-(3-Amino-1,2,4-oxadiazol-5-yl)-5-(4-ethylphenyl)piperidin-1-yl](4-hydroxypiperidin-1-yl)methanone

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

Under argon, a solution of 2.50 g (6.31 mmol) of the carboxylic acid from Example 21A in 50 ml of DMF was admixed at RT with 3.94 g (7.57 mmol) of PYBOP and 2.20 ml (12.6 mmol) of N,N′-diisopropylethylamine. Subsequently, the mixture was stirred at RT for 30 min and then the solution was added dropwise within 1.5 h to a suspension of 5.04 g (18.9 mmol) of hydroxyguanidine hemisulphate hemihydrate, 3.30 ml (18.9 mmol) of N,N′-diisopropylethylamine and 4 Å molecular sieve. The reaction mixture was stirred at RT for 1 h and then filtered through a frit. The residue was washed with 50 ml of DMF and then the combined organic phases were stirred at 130° C. (preheated oil bath) for 40 min. Subsequently, the solvent was removed under reduced pressure and the residue was admixed with 30 ml of diethyl ether and 30 ml of 1 N aqueous sodium hydroxide solution, and stirred vigorously for 24 h. The organic phase was removed and the aqueous phase was extracted with dichloromethane. The organic phase was dried over magnesium sulphate, filtered and concentrated under reduced pressure. Yield: 3.00 g (77% of theory, purity 65%)

後処理

  1. stirringThe reaction mixture was stirred at RT for 1 h
  2. filtrationfiltered through a frit
  3. washThe residue was washed with 50 ml of DMF
  4. stirringthe combined organic phases were stirred at 130° C. (preheated oil bath) for 40 min
  5. customSubsequently, the solvent was removed under reduced pressure
  6. stirringstirred vigorously for 24 h
  7. customThe organic phase was removed
  8. extractionthe aqueous phase was extracted with dichloromethane
  9. dry with materialThe organic phase was dried over magnesium sulphate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-d97393fac12844d796739af36d7fbb99
出典データセット
uspto-grants-2011_12
特許番号
US08084469B2

反応ノート

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