4-Methylmorpholine → N-[1-(4-cyano-3-fluoro-phenyl)-3-cyclopropyl-1-(3-methyl-3H-imidazol-4-yl)-prop-2-ynyl]-3-(3-methoxy-benzenesulfonylamino)-propionamide

HRID 1060901노트

반응식

HRID 1060901 반응식
Cl.Cl.[NH2:3][C:4]([C:16]1[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[C:18]([F:24])[CH:17]=1)([C:6]1[N:7]([C:11]#CC2CC2)[CH:8]=[N:9][CH:10]=1)[CH3:5].[CH3:25][O:26][C:27]1[CH:28]=[C:29]([S:33]([NH:36][CH2:37][CH2:38][C:39]([OH:41])=O)(=[O:35])=[O:34])[CH:30]=[CH:31][CH:32]=1.CN([P+](ON1N=NC2C=[CH:57][CH:58]=[CH:59][C:54]1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.ON1C2N=CC=CC=2N=N1.CN1CCOCC1>CN(C=O)C>[C:20]([C:19]1[CH:22]=[CH:23][C:16]([C:4]([NH:3][C:39](=[O:41])[CH2:38][CH2:37][NH:36][S:33]([C:29]2[CH:30]=[CH:31][CH:32]=[C:27]([O:26][CH3:25])[CH:28]=2)(=[O:34])=[O:35])([C:6]2[N:7]([CH3:11])[CH:8]=[N:9][CH:10]=2)[C:5]#[C:57][CH:58]2[CH2:54][CH2:59]2)=[CH:17][C:18]=1[F:24])#[N:21]

참가 물질

7

반응물 5

HCID 79724-MethylmorpholineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 181649HOAtHCID 186294403-(3-Methoxy-benzenesulfonylamino)-propionic acidHCID 18629460(+)-4-[1-Amino-1-(3-(cyclopropylethynyl)-3H-imidazol-4-yl)-ethyl]-2-fluoro-benzonitrile bishydrochloride

생성물 1

HCID 18629425N-[1-(4-cyano-3-fluoro-phenyl)-3-cyclopropyl-1-(3-methyl-3H-imidazol-4-yl)-prop-2-ynyl]-3-(3-methoxy-benzenesulfonylamino)-propionamide

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

(+)-4-[1-Amino-1-(3-(cyclopropylethynyl)-3H-imidazol-4-yl)-ethyl]-2-fluoro-benzonitrile bishydrochloride (0.120 g, 0.408 mmol), 3-(3-methoxy-benzenesulfonylamino)-propionic acid (Example 7, Step B) (0.1273 g, 0.49 mmol), Bop reagent (0.186 g, 0.49 mmol), 1-hydroxy-7-aza-benzotriazole (HOAT) (0.067 g, 0.49 mmol) and N-methyl morpholine(0.134 mL, 1.22 mmol) were dissolved in DMF (5.0 mL) and stirred for 18 h. The reaction mixture was concentrated in vacuo, partitioned between EtOAc and saturated NaHCO3 solution, the organic layer separated, washed with H2O, brine, and dried (MgSO4). Filtration and concentration in vacuo gave the title compound after chromatography on an ISCO Combiflash eluting with 2-5% MeOH/CH2Cl2 with NH4OH. MS (M+1) 536.

후처리

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. custompartitioned between EtOAc and saturated NaHCO3 solution
  3. customthe organic layer separated
  4. washwashed with H2O, brine
  5. dry with materialdried (MgSO4)
  6. filtrationFiltration and concentration in vacuo

출처 및 근거

ORD 기록
ord-80572eea8a934eedb71ee46e6836ce84
출처 데이터셋
uspto-grants-2003_02
특허 번호
US06525074B2

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