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Diisopropylethylamine → 3-cyano-N-{5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-thiophen-3-ylmethyl}-propionamide

HRID 68571
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HRID 68571 반응식
[C:1]([CH2:3][CH2:4][C:5]([OH:7])=O)#[N: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.[Cl:50][C:51]1[CH:52]=[C:53]([C:58]2([C:71]([F:74])([F:73])[F:72])[O:62][N:61]=[C:60]([C:63]3[S:67][C:66]([CH3:68])=[C:65]([CH2:69][NH2:70])[CH:64]=3)[CH2:59]2)[CH:54]=[C:55]([Cl:57])[CH:56]=1>ClCCl>[C:1]([CH2:3][CH2:4][C:5]([NH:70][CH2:69][C:65]1[CH:64]=[C:63]([C:60]2[CH2:59][C:58]([C:53]3[CH:54]=[C:55]([Cl:57])[CH:56]=[C:51]([Cl:50])[CH:52]=3)([C:71]([F:73])([F:74])[F:72])[O:62][N:61]=2)[S:67][C:66]=1[CH3:68])=[O:7])#[N:2]
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참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 2630863-Cyanopropanoic acidHCID 2724699PyBOPHCID 68293128C-{5-(5-[3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-thiophen-3-yl}-methylamine

생성물 1

HCID 867066493-cyano-N-{5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-thiophen-3-ylmethyl}-propionamide
수율 19.6%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

3-Cyanopropionic acid (104 mg) and PyBOP (400 mg) are added to a solution of DIPEA (0.36 ml) and C-{5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-thiophen-3-yl}-methylamine (286 mg, Example 1, step F) in dichloromethane (5 ml). After 4 hours at RT, the reaction is quenched with water. The aqueous phase is separated and further extracted two times with dichloromethane. The organic phases are combined, dried over MgSO4 and concentrated in vacuo. The crude product is purified on a semi-preparative HPLC to yield 3-cyano-N-{5-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-thiophen-3-ylmethyl}-propionamide (compound 1.39, 67 mg) as a beige resin. MS (HPLC/MS): 491 (MH+). Retention time: 1.90 min.

후처리

  1. customthe reaction is quenched with water
  2. customThe aqueous phase is separated
  3. extractionfurther extracted two times with dichloromethane
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product is purified on a semi-preparative HPLC

출처 및 근거

ORD 기록
ord-f4278cb2efd143fc9619f1856ebad428
출처 데이터셋
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08822466B2

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