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

HRID 1098781Notes

Reaction equation

HRID 1098781 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-d6bbfb92b0294837bac4576ee342fdbe
Source dataset
uspto-grants-2012_03
Patent number
US08143290B2

Reaction notes

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