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

HRID 661209노트

반응식

HRID 661209 반응식
[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

참가 물질

6

반응물 4

HCID 81531Diisopropylethylamine2회HCID 2724699PyBOPHCID 580026415-(4-Ethylphenyl)-1-[(4-hydroxypiperidin-1-yl)carbonyl]piperidine-3-carboxylic acidHCID 178513195HCID 178513195, 화합물

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

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%)

후처리

  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

출처 및 근거

ORD 기록
ord-d97393fac12844d796739af36d7fbb99
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08084469B2

반응 노트

불러오는 중…