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 1060901Notes

Reaction equation

HRID 1060901 reaction equation
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]

Participants

7

Reactant 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

Product 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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(+)-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.

Workup

  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

Sources & evidence

ORD record
ord-80572eea8a934eedb71ee46e6836ce84
Source dataset
uspto-grants-2003_02
Patent number
US06525074B2

Reaction notes

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