Diisopropylethylamine → {3-[4-(Difluoromethoxy)phenyl]-5-(3-ethoxy-1,2,4-oxadiazol-5-yl)piperidin-1-yl}(1-oxidothio-morpholin-4-yl)methanone

HRID 661313노트

반응식

HRID 661313 반응식
[F:1][CH:2]([F:28])[O:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[CH2:15][N:14]([C:16]([N:18]3[CH2:23][CH2:22][S:21](=[O:24])[CH2:20][CH2:19]3)=[O:17])[CH2:13][CH:12]([C:25](O)=[O:26])[CH2:11]2)=[CH:6][CH:5]=1.O[N:30]=[C:31]([O:33][CH2:34][CH3:35])[NH2:32].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C>[F:1][CH:2]([F:28])[O:3][C:4]1[CH:5]=[CH:6][C:7]([CH:10]2[CH2:11][CH:12]([C:25]3[O:26][N:32]=[C:31]([O:33][CH2:34][CH3:35])[N:30]=3)[CH2:13][N:14]([C:16]([N:18]3[CH2:23][CH2:22][S:21](=[O:24])[CH2:20][CH2:19]3)=[O:17])[CH2:15]2)=[CH:8][CH:9]=1

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 581165795-[4-(Difluoromethoxy)phenyl]-1-[(1-oxidothiomorpholin-4-yl)carbonyl]piperidine-3-carboxylic acidHCID 76223295ethyl N-hydroxyimidocarbamate

생성물 1

HCID 58116505{3-[4-(Difluoromethoxy)phenyl]-5-(3-ethoxy-1,2,4-oxadiazol-5-yl)piperidin-1-yl}(1-oxidothio-morpholin-4-yl)methanone

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

185 mg (0.37 mmol) of the compound from Example 42A and 50 mg (0.48 mmol) of ethyl N′-hydroxyimidocarbamate [G. Zinner, G. Nebel, Arch. Pharm. 1970, 303, 385-390] were initially charged in 1.0 ml of DMF and reacted with 210 mg (0.55 mmol) of HATU and 0.19 ml (143 mg, 1.1 mmol) of N,N-diisopropylethylamine. The mixture was stirred at RT for 15 minutes and then the reaction mixture was partitioned between water and ethyl acetate. The organic phase was washed repeatedly with water, dried over sodium sulphate and concentrated under reduced pressure. The residue was dissolved in 2.0 ml of acetic acid and heated to reflux for 1 h. The reaction mixture was purified by means of preparative HPLC. Yield: 62 mg (33% of theory)

후처리

  1. customthe reaction mixture was partitioned between water and ethyl acetate
  2. washThe organic phase was washed repeatedly with water
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in 2.0 ml of acetic acid
  6. temperatureheated
  7. temperatureto reflux for 1 h
  8. customThe reaction mixture was purified by means of preparative HPLC

출처 및 근거

ORD 기록
ord-de8b648eea83467c9b3623dc0bc2a765
출처 데이터셋
uspto-grants-2011_12
특허 번호
US08084469B2

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