Trichloroacetyl chloride → 3-[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-imidazol-4-yl]-propionic acid methyl ester

HRID 900250Notes

Reaction equation

HRID 900250 reaction equation
[CH3:1][O:2][C:3](=[O:23])[CH2:4][CH2:5][C:6]1[N:7]=[CH:8][N:9]([CH2:11][C:12]2[CH:16]=[C:15]([C:17]3[S:18][C:19]([Cl:22])=[CH:20][CH:21]=3)[O:14][N:13]=2)[CH:10]=1.CCN(CC)CC.ClC(Cl)(Cl)[C:33](Cl)=[O:34].Cl.Cl.[CH:40]([N:43]1[CH2:48][CH2:47][CH:46]([NH2:49])[CH2:45][CH2:44]1)([CH3:42])[CH3:41]>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:23])[CH2:4][CH2:5][C:6]1[N:7]=[C:8]([C:33](=[O:34])[NH:49][CH:46]2[CH2:47][CH2:48][N:43]([CH:40]([CH3:42])[CH3:41])[CH2:44][CH2:45]2)[N:9]([CH2:11][C:12]2[CH:16]=[C:15]([C:17]3[S:18][C:19]([Cl:22])=[CH:20][CH:21]=3)[O:14][N:13]=2)[CH:10]=1

Participants

6

Reactant 4

HCID 6420Trichloroacetyl chlorideHCID 8471Triethylamine2×HCID 177503401-(Propan-2-yl)piperidin-4-amine dihydrochlorideHCID 691120863-{1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-imidazol-4-yl}-propionic acid methyl ester

Product 1

HCID 103693953-[1-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-2-(1-isopropyl-piperidin-4-ylcarbamoyl)-1H-imidazol-4-yl]-propionic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 3-{1-[5-(5-chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-1H-imidazol-4-yl}-propionic acid methyl ester (140 mg) and NEt3 (70 μL) in DCM (5 mL) was added a solution of trichloroacetyl chloride (50 μL) in DCM (1 mL) dropwise at 0° C. The mixture was stirred for 5 min at 0° C. and for 30 min at RT. More NEt3 (280 μL) and 1-isopropyl-piperidin-4-ylamine dihydrochloride (88 mg) were added and stirring was continued for 2 h at RT. The mixture was concentrated and the residue was purified by preparative HPLC. The fractions containing the product were evaporated to provide 47 mg of the title compound as its trifluoroacetate salt. MS (ESI+): m/e=520, chloro pattern.

Workup

  1. stirringstirring
  2. waitwas continued for 2 h at RT
  3. concentrationThe mixture was concentrated
  4. customthe residue was purified by preparative HPLC
  5. additionThe fractions containing the product
  6. customwere evaporated

Sources & evidence

ORD record
ord-c5fca71f6558437a8b060e04aa1b2b94
Source dataset
uspto-grants-2008_04
Patent number
US07358268B2

Reaction notes

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