Hydrochloric Acid → 5-fluoro-N-[6-fluoro-5-(5-methyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-2-methoxy-nicotinamide

HRID 510000Notes

Reaction equation

HRID 510000 reaction equation
[F:1][C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[CH:4][C:3]=1[CH2:9][C:10]1[C:18]2[C:13](=[N:14][CH:15]=[C:16]([CH3:19])[CH:17]=2)[NH:12][CH:11]=1.[F:20][C:21]1[CH:22]=[N:23][C:24]([O:30][CH3:31])=[C:25]([CH:29]=1)[C:26](Cl)=[O:27].N1C=CC=CC=1.Cl>O1CCCC1>[F:20][C:21]1[CH:22]=[N:23][C:24]([O:30][CH3:31])=[C:25]([CH:29]=1)[C:26]([NH:8][C:6]1[CH:5]=[CH:4][C:3]([CH2:9][C:10]2[C:18]3[C:13](=[N:14][CH:15]=[C:16]([CH3:19])[CH:17]=3)[NH:12][CH:11]=2)=[C:2]([F:1])[N:7]=1)=[O:27]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 582592126-fluoro-5-(5-methyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-ylamineHCID 582594585-Fluoro-2-methoxy-nicotinoyl chloride

Product 1

HCID 672001815-fluoro-N-[6-fluoro-5-(5-methyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-2-methoxy-nicotinamideYield 62.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In a reaction flask, 6-fluoro-5-(5-methyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-ylamine (137, 100 mg, 0.3902 mmol) was combined with 5-fluoro-2-methoxy-nicotinoyl chloride (151, 81.37 mg, 0.4292 mmol), 3.00 mL of tetrahydrofuran, and pyridine (0.06312 mL, 0.7804 mmol). The reaction was stirred at room temperature overnight, then poured into aqueous 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography, eluting with 1-5% methanol in dichloromethane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound (P-2168, 100 mg). MS (ESI) [M+H+]+=409.9.

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationthe filtrate concentrated under vacuum
  5. customThe resulting material was purified by silica gel column chromatography
  6. washeluting with 1-5% methanol in dichloromethane
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-02b318f283744620b4e52d6154e06729
Source dataset
uspto-grants-2015_08
Patent number
US09096593B2

Reaction notes

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