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Triethylamine → 1-ethyl-5-trifluoromethoxy-1H-indole-2-carboxylic acid {6-[(2-methoxy-ethyl)-methyl-amino]-pyridin-3-yl}-amide hydrochloride

HRID 1645351
Notes
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Reaction equation

HRID 1645351 reaction equation
[CH2:1]([N:3]1[C:11]2[C:6](=[CH:7][C:8]([O:12][C:13]([F:16])([F:15])[F:14])=[CH:9][CH:10]=2)[CH:5]=[C:4]1[C:17]([OH:19])=O)[CH3:2].C(Cl)(=O)C([Cl:23])=O.[CH3:26][O:27][CH2:28][CH2:29][N:30]([CH3:38])[C:31]1[CH:36]=[CH:35][C:34]([NH2:37])=[CH:33][N:32]=1.C(N(CC)CC)C>C(Cl)Cl.CN(C=O)C>[ClH:23].[CH3:26][O:27][CH2:28][CH2:29][N:30]([CH3:38])[C:31]1[N:32]=[CH:33][C:34]([NH:37][C:17]([C:4]2[N:3]([CH2:1][CH3:2])[C:11]3[C:6]([CH:5]=2)=[CH:7][C:8]([O:12][C:13]([F:14])([F:15])[F:16])=[CH:9][CH:10]=3)=[O:19])=[CH:35][CH:36]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 52937159N2-(2-methoxyethyl)-N2-methylpyridine-2,5-diamineHCID 593651711-ethyl-5-trifluoromethoxy-1H-indole-2-carboxylic acid

Product 1

HCID 667724081-ethyl-5-trifluoromethoxy-1H-indole-2-carboxylic acid {6-[(2-methoxy-ethyl)-methyl-amino]-pyridin-3-yl}-amide hydrochloride

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 1-ethyl-5-trifluoromethoxy-1H-indole-2-carboxylic acid (65 mg, 0.24 mmol), CH2Cl2 (5 mL), and catalytic amount of DMF was stirred under Ar, and oxalyl chloride (2M in dichloromethane, 250 μL, 0.5 mmol) was dripped into the mixture over 5 min. The mixture was stirred at room temperature for 1.0 hr and then concentrated to dryness. Benzene was added and the solution was evaporated to dryness again. The residue was re-dissolved in 5 mL of CH2Cl2 and dripped, under Ar, into a solution of N-(2-methoxy-ethyl)-N-methyl-pyridine-2,5-diamine (43.0 mg, 0.24 mmol), and triethylamine (0.52 mg, 0.5 mmol) in 5 mL of CH2Cl2. The reaction was stirred at room temperature for 0.5 hr then concentrated and the residue was taken up in 50 mL of EtOAc and washed with 50 mL of saturated ammonium chloride, brine and dried with anhydrous sodium sulfate. The solvent was removed, and the crude product was purified by flash chromatography (hexanes:EtOAc) followed by conversion to HCl salt with 1N HCl in ether to afford the product, 1-ethyl-5-trifluoromethoxy-1H-indole-2-carboxylic acid {6-[(2-methoxy-ethyl)-methyl-amino]-pyridin-3-yl}-amide hydrochloride, as a pink solid (44 mg, 42% yield). LCMS for C21H23F3N4O3 calcd. (m/e) 436, observed 437 (M+H).

Workup

  1. concentrationconcentrated to dryness
  2. additionBenzene was added
  3. customthe solution was evaporated to dryness again
  4. dissolutionThe residue was re-dissolved in 5 mL of CH2Cl2
  5. stirringThe reaction was stirred at room temperature for 0.5 hr
  6. concentrationthen concentrated
  7. washwashed with 50 mL of saturated ammonium chloride, brine
  8. dry with materialdried with anhydrous sodium sulfate
  9. customThe solvent was removed
  10. customthe crude product was purified by flash chromatography (hexanes:EtOAc)

Sources & evidence

ORD record
ord-3a162519961c43b8b5c694683a9aedf7
Source dataset
uspto-grants-2012_02
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08124766B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes