N,N-二异丙基乙胺 → Tetrahydro-furan-3-carboxylic acid {2-methyl-5-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-furan-3-ylmethyl}-amide

HRID 68581

反应方程式

HRID 68581 反应方程式
[O:1]1[CH2:5][CH2:4][CH:3]([C:6]([OH:8])=O)[CH2:2]1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[CH3:51][C:52]1[O:53][C:54]([C:59]2[CH2:63][C:62]([C:68]3[CH:73]=[C:72]([Cl:74])[C:71]([Cl:75])=[C:70]([Cl:76])[CH:69]=3)([C:64]([F:67])([F:66])[F:65])[O:61][N:60]=2)=[CH:55][C:56]=1[CH2:57][NH2:58]>ClCCl>[CH3:51][C:52]1[O:53][C:54]([C:59]2[CH2:63][C:62]([C:68]3[CH:73]=[C:72]([Cl:74])[C:71]([Cl:75])=[C:70]([Cl:76])[CH:69]=3)([C:64]([F:66])([F:65])[F:67])[O:61][N:60]=2)=[CH:55][C:56]=1[CH2:57][NH:58][C:6]([CH:3]1[CH2:4][CH2:5][O:1][CH2:2]1)=[O:8]

参与物

6

反应物 4

HCID 81531N,N-二异丙基乙胺HCID 27246991H-苯并三唑-1-基氧三吡咯烷基六氟磷酸盐HCID 46613173-四氢呋喃甲酸HCID 86706655C-{2-methyl-5-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-furan-3-yl}-methylamine

产物 1

HCID 86706656Tetrahydro-furan-3-carboxylic acid {2-methyl-5-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-furan-3-ylmethyl}-amide收率 76.9%

试剂、催化剂与溶剂 1

HCID 6344二氯甲烷溶剂

实验过程

Tetrahydro-furan-3-carboxylic acid (81 mg), PyBOP (268 mg) and DIPEA (0.244 ml) are added to a solution of C-{2-methyl-5-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-furan-3-yl}-methylamine (200 mg) in dichloromethane (4 ml). After 24 hours at room temperature, the reaction is quenched with water. The reaction mixture is extracted three times with dichloromethane. The combined organic phases are washed with a saturated solution of NaHCO3 and with a saturated aqueous solution of NaCl, dried over Na2SO4 and concentrated in vacuo. The crude product is purified on a semi-preparative HPLC to yield tetrahydro-furan-3-carboxylic acid {2-methyl-5-[5-(3,4,5-trichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-furan-3-ylmethyl}-amide (189 mg, compound 2.3 in Table 2) as a white foam. MS (HPLC/MS): 525 (MH+). Retention time: 1.97 min.

后处理

  1. customthe reaction is quenched with water
  2. extractionThe reaction mixture is extracted three times with dichloromethane
  3. washThe combined organic phases are washed with a saturated solution of NaHCO3 and with a saturated aqueous solution of NaCl
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude product is purified on a semi-preparative HPLC

来源与证据

ORD记录
ord-4162567a08bb4382b1be2cae6394aba4
来源数据集
uspto-grants-2014_09
专利号
US08822466B2

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