Diisopropylethylamine → 3-[2-[4-[5-Phenyl-4-[(2,2,2-trifluoroethoxy)methyl]oxazol-2-yl]piperidino]ethyl]-6-methoxybenzenesulfonamide

HRID 2288992Notes

Reaction equation

HRID 2288992 reaction equation
[C:1]1([C:7]2[O:11][C:10]([CH:12]3[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)=[N:9][C:8]=2[CH2:18][O:19][CH2:20][C:21]([F:24])([F:23])[F:22])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[CH2:26][CH2:27][C:28]1[CH:29]=[CH:30][C:31]([O:38][CH3:39])=[C:32]([S:34]([NH2:37])(=[O:36])=[O:35])[CH:33]=1.N[C@H](C(O)=O)CC1C=C2C(C=CC=C2)=CC=1.CCN(C(C)C)C(C)C>O1CCOCC1>[CH3:39][O:38][C:31]1[CH:30]=[CH:29][C:28]([CH2:27][CH2:26][N:15]2[CH2:16][CH2:17][CH:12]([C:10]3[O:11][C:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)=[C:8]([CH2:18][O:19][CH2:20][C:21]([F:22])([F:23])[F:24])[N:9]=3)[CH2:13][CH2:14]2)=[CH:33][C:32]=1[S:34]([NH2:37])(=[O:36])=[O:35]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 1859152-NaphthylalanineHCID 187004435-(2-Chloroethyl)-2-methoxy-benzenesulfonamideHCID 187004502-(4-Piperidinyl)-4-(2,2,2-trifluoroethoxymethyl)-5-phenyloxazole

Product 1

HCID 187004673-[2-[4-[5-Phenyl-4-[(2,2,2-trifluoroethoxy)methyl]oxazol-2-yl]piperidino]ethyl]-6-methoxybenzenesulfonamide

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To 4-[5-phenyl-4-(2,2,2-trifluoro-ethoxymethyl)-oxazol-2-yl]-piperidine (0.750 g), prepared as in Intermediate 5, in dioxane is added 5-(2-chloro-ethyl)-2-methoxy-benzenesulfonamide (0.716 g), prepared as in Intermediate 1, Nal (0.429 g) and DIEA (1.15 ml). After heating at 100° C. for 18 hours, the reaction mixture is partitioned between EtOAc and dilute NaHCO3 solution. The organic phase is washed with saturated brine, dried (NaSO4) and concentrated. The residue is dissolved in CHCl3 (20 mL) and preadsorbed onto silica gel. Purification by flash chromatography on silica gel using a MeOH-EtOAc gradient (2-10%), followed by radial chromotography using a MeOH-CH2Cl2 gradient (1-5%) and crystallization from CH2Cl2 -EtOAc affords the title compound as a white solid.

Workup

  1. customthe reaction mixture is partitioned between EtOAc and dilute NaHCO3 solution
  2. washThe organic phase is washed with saturated brine
  3. dry with materialdried (NaSO4)
  4. concentrationconcentrated
  5. dissolutionThe residue is dissolved in CHCl3 (20 mL)
  6. customPurification by flash chromatography on silica gel using a MeOH-EtOAc gradient (2-10%)
  7. customa MeOH-CH2Cl2 gradient (1-5%) and crystallization from CH2Cl2 -EtOAc

Sources & evidence

ORD record
ord-d57a526d96084f2eb2bdb0037994045c
Source dataset
uspto-grants-2000_07
Patent number
US06090825

Reaction notes

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