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 1060901ノート

反応式

HRID 1060901 の反応式
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]

参加物

7

反応物 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

生成物 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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

(+)-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.

後処理

  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

出典と根拠

ORDレコード
ord-80572eea8a934eedb71ee46e6836ce84
出典データセット
uspto-grants-2003_02
特許番号
US06525074B2

反応ノート

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