Triethylamine → N-{(1S)-1-[(S)-(3-fluorophenyl)-{[1-(4-fluorophenyl)-1H-indazole-5-yl]oxy}methyl}-3-methyl-butyl}-2-methoxyacetamide

HRID 1098892Notes

Reaction equation

HRID 1098892 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]([O:15][C:16]2[CH:17]=[C:18]3[C:22](=[CH:23][CH:24]=2)[N:21]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[N:20]=[CH:19]3)[C@H:9]([CH2:11][CH:12]([CH3:14])[CH3:13])[NH2:10])[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[CH3:39][O:40][CH2:41][C:42](Cl)=[O:43]>ClCCl>[F:1][C:2]1[CH:3]=[C:4]([C@H:8]([O:15][C:16]2[CH:17]=[C:18]3[C:22](=[CH:23][CH:24]=2)[N:21]([C:25]2[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=2)[N:20]=[CH:19]3)[C@@H:9]([NH:10][C:42](=[O:43])[CH2:41][O:40][CH3:39])[CH2:11][CH:12]([CH3:14])[CH3:13])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 96623Methoxyacetyl chlorideHCID 66812773(alphaS)-3-Fluoro-beta-[[1-(4-fluorophenyl)-1H-indazole-5-yl]oxy]-alpha-(2-methylpropyl)benzeneethanamine

Product 1

HCID 66812792N-{(1S)-1-[(S)-(3-fluorophenyl)-{[1-(4-fluorophenyl)-1H-indazole-5-yl]oxy}methyl}-3-methyl-butyl}-2-methoxyacetamideYield 68%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(αS)-3-Fluoro-β-[[1-(4-fluorophenyl)-1H-indazole-5-yl]oxy]-α-(2-methylpropyl)benzeneethanamine (76.4 mg, 0.18 mmol) is dissolved in 7 mL dichloromethane. Triethylamine (0.06 mL, 0.44 mmol) and 2-methoxyacetyl chloride (0.02 mL, 0.22 mmol) are added. After stirring overnight the reaction mixture is diluted with dichloromethane, washed with water and brine and dried over Na2SO4. After filtration the solvent is evaporated and the residue is purified by chromatography (silicagel, eluents: ethylacetate/hexane). The obtained mixture of the two stereoisomers is separated by HPLC (Chiralpak AD-H 5 μm, eluents: hexane/ethanol) yielding 3.7 mg (10.2%) of the title stereoisomer and 24.7 mg (68%) of the stereoisomer N-{(1S)-1-[(S)-(3-fluorophenyl)-{[1-(4-fluorophenyl)-1H-indazole-5-yl]oxy}methyl}-3-methyl-butyl}-2-methoxyacetamide.

Workup

  1. washwashed with water and brine
  2. dry with materialdried over Na2SO4
  3. filtrationAfter filtration the solvent
  4. customis evaporated
  5. customthe residue is purified by chromatography (silicagel, eluents: ethylacetate/hexane)
  6. additionThe obtained mixture of the two stereoisomers
  7. customis separated by HPLC (Chiralpak AD-H 5 μm, eluents: hexane/ethanol)

Sources & evidence

ORD record
ord-fd11c37bd6214566a30572ad33f7b674
Source dataset
uspto-grants-2012_03
Patent number
US08143290B2

Reaction notes

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