Trifluoroacetic acid → [5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-6-fluoro-pyridin-2-yl]-(5-fluoro-pyridin-3-ylmethyl)-amine

HRID 509989Notes

Reaction equation

HRID 509989 reaction equation
C(OC([N:8]1[C:12]2=[N:13][CH:14]=[C:15]([Cl:17])[CH:16]=[C:11]2[C:10]([CH2:18][C:19]2[C:20]([F:41])=[N:21][C:22]([N:25](C(OC(C)(C)C)=O)[CH2:26][C:27]3[CH:28]=[N:29][CH:30]=[C:31]([F:33])[CH:32]=3)=[CH:23][CH:24]=2)=[CH:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[Cl:17][C:15]1[CH:16]=[C:11]2[C:10]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([NH:25][CH2:26][C:27]4[CH:28]=[N:29][CH:30]=[C:31]([F:33])[CH:32]=4)=[N:21][C:20]=3[F:41])=[CH:9][NH:8][C:12]2=[N:13][CH:14]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58259261HCID 58259261, compound

Product 1

HCID 52935810[5-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-6-fluoro-pyridin-2-yl]-(5-fluoro-pyridin-3-ylmethyl)-amineYield 53.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 3-{6-[tert-butoxycarbonyl-(5-fluoro-pyridin-3-ylmethyl)-amino]-2-fluoro-pyridin-3-ylmethyl}-5-chloro-pyrrolo[2,3-b]pyridine-1-carboxylic acid tert-butyl ester (144, 0.280 g, 0.478 mmol) in 10.0 mL of dichloromethane, trifluoroacetic acid (1.00 mL, 13.0 mmol) was added and the reaction stirred at room temperature overnight. This was pooled with a separate reaction run similarly and concentrated under vacuum. The resulting material was combined with aqueous potassium carbonate and ethyl acetate and mixed. The aqueous layer was separated and 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 20% ethyl acetate in hexane. Appropriate fractions were combined and the solvent removed under vacuum to provide the desired compound (P-2001, 99 mg). MS (ESI) [M+H+]+=386.0.

Workup

  1. customThis was pooled with a separate reaction
  2. concentrationconcentrated under vacuum
  3. additionmixed
  4. customThe aqueous layer was separated
  5. dry with materialthe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated under vacuum
  8. customThe resulting material was purified by silica gel column chromatography
  9. washeluting with 20% ethyl acetate in hexane
  10. customthe solvent removed under vacuum

Sources & evidence

ORD record
ord-962bcb7cf9b24086a1921c8f5228ffb4
Source dataset
uspto-grants-2015_08
Patent number
US09096593B2

Reaction notes

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