Triethylamine → N-[(1R,2S)-1-[1-(4-fluorophenyl)indazol-5-yl]oxy-1-(4-methylsulfanylphenyl)propan-2-yl]-2-methoxy-acetamide

HRID 13016

Reaction equation

HRID 13016 reaction equation
[CH3:1][O:2][CH2:3][C:4](Cl)=[O:5].Cl.[F:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[C:23]3[C:18](=[CH:19][C:20]([O:24][C@H:25]([C:29]4[CH:34]=[CH:33][C:32]([S:35][CH3:36])=[CH:31][CH:30]=4)[C@@H:26]([NH2:28])[CH3:27])=[CH:21][CH:22]=3)[CH:17]=[N:16]2)=[CH:11][CH:10]=1.C(N(CC)CC)C>C1COCC1>[F:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[C:23]3[C:18](=[CH:19][C:20]([O:24][C@H:25]([C:29]4[CH:30]=[CH:31][C:32]([S:35][CH3:36])=[CH:33][CH:34]=4)[C@@H:26]([NH:28][C:4](=[O:5])[CH2:3][O:2][CH3:1])[CH3:27])=[CH:21][CH:22]=3)[CH:17]=[N:16]2)=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 96623Methoxyacetyl chlorideHCID 66687724(1R,2S)-1-{[1-(4-fluorophenyl)-1H-indazol-5-yl]oxy}-1-[4-(methylthio)phenyl]propan-2-amine hydrochloride

Product 1

HCID 25013491N-[(1R,2S)-1-[1-(4-fluorophenyl)indazol-5-yl]oxy-1-(4-methylsulfanylphenyl)propan-2-yl]-2-methoxy-acetamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methoxyacetyl chloride (10 μL, 0.11 mmol) was added to a suspension of (1R,2S)-1-{[1-(4-fluorophenyl)-1H-indazol-5-yl]oxy}-1-[4-(methylthio)phenyl]propan-2-amine hydrochloride (40 mg, 0.09 mmol) and triethylamine (42 μL, 0.3 mmol) in THF (1 mL). The reaction was stirred at r.t. for 30 min and then quenched by adding water, the mixture was diluted with a small volume of MeCN so that a solution was obtained. This crude mixture was purified by semi-preparative HPLC using a Kromasil® C18 250×20 mm, 5 μm column. Flow 10 mL/min, 20 min gradient of 20%-90% MeCN in water followed by isocratic final concentration until product had eluted. UV=254 nm was used for detection. Fractions with product was combined and lyophilized to afford the title compound as a colourless solid. Yield 30 mg (69%).

Workup

  1. customquenched
  2. additionby adding water
  3. additionthe mixture was diluted with a small volume of MeCN so that a solution
  4. customwas obtained
  5. customThis crude mixture was purified by semi-preparative HPLC
  6. customFlow 10 mL/min, 20 min gradient of 20%-90% MeCN in water
  7. concentrationconcentration until product
  8. washhad eluted

Sources & evidence

ORD record
ord-e5c732e75a6f47b9bb790ed140987727
Source dataset
uspto-grants-2010_06
Patent number
US07728030B2

Linked notes

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