Triethylamine → HCID 66813055, compound

HRID 1098895Notes

Reaction equation

HRID 1098895 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]([O:20][C:21]2[CH:22]=[C:23]3[C:27](=[CH:28][CH:29]=2)[N:26]([C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)[N:25]=[CH:24]3)[C@H:9]([CH2:11][O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[NH2:10])[CH:5]=[CH:6][CH:7]=1.C(N(CC)CC)C.[CH3:44][O:45][CH2:46][C:47](Cl)=[O:48]>ClCCl>[F:1][C:2]1[CH:3]=[C:4]([CH:8]([O:20][C:21]2[CH:22]=[C:23]3[C:27](=[CH:28][CH:29]=2)[N:26]([C:30]2[CH:31]=[CH:32][C:33]([F:36])=[CH:34][CH:35]=2)[N:25]=[CH:24]3)[C@@H:9]([NH:10][C:47](=[O:48])[CH2:46][O:45][CH3:44])[CH2:11][O:12][CH2:13][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 96623Methoxyacetyl chlorideHCID 66812817HCID 66812817, compound

Product 1

HCID 66813055HCID 66813055, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

(αS)-3-Fluoro-β-[[1-(4-fluorophenyl)-1H-indazole-5-yl]oxy]-α-[(phenylmethoxy)methyl]benzeneethanamine is synthesized in analogy to the sequence previously described in example 1: commercially available Boc-Ser(Bn)-OH is transformed into its Weinreb-amide. Reduction to the aldehyde with LiAl4, reaction with 3-fluorophenylgrignard, cleavage of the tert.-butyloxycarbonyl protecting group, liberation of the amine from the hydrochloride and etherification with 1-(4-fluorophenyl)-5-iodo-1H-indazole gives the desired amine. This amine (123.3 mg, 0.25 mmol) is dissolved in 10 mL of dichloromethane. Triethylamine (0.084 mL, 0.61 mmol) and 0.028 mL (0.3 mmol) 2-methoxyacetylchloride are added. The reaction mixture is stirred overnight at r.t., then diluted with dichloromethane, washed with water and brine and dried over Na2SO4. After filtration the solvent is evaporated and the residue purified by chromatography (silicagel, eluents: ethyl acetate/hexane). 79.1 mg (55.9%) of the title compound as a mixture of stereoisomers are isolated.

Workup

  1. washwashed with water and brine
  2. dry with materialdried over Na2SO4
  3. filtrationAfter filtration the solvent
  4. customis evaporated
  5. customthe residue purified by chromatography (silicagel, eluents: ethyl acetate/hexane)
  6. addition79.1 mg (55.9%) of the title compound as a mixture of stereoisomers
  7. customare isolated

Sources & evidence

ORD record
ord-4f334e3595014350aa88adcc6a2e17a2
Source dataset
uspto-grants-2012_03
Patent number
US08143290B2

Reaction notes

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