Methylamine → 3-{2-fluoro-6-[(5-fluoro-2-methoxy-pyridin-3-ylmethyl)-amino]-pyridin-3-ylmethyl}-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid methylamide

HRID 510013Notes

Reaction equation

HRID 510013 reaction equation
C[O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:13]([CH2:14][C:15]3[C:16]([F:32])=[N:17][C:18]([NH:21][CH2:22][C:23]4[C:24]([O:30][CH3:31])=[N:25][CH:26]=[C:27]([F:29])[CH:28]=4)=[CH:19][CH:20]=3)=[CH:12][NH:11][C:8]2=[N:9][CH:10]=1)=O.[CH3:33][NH2:34]>>[CH3:33][NH:34][C:3]([C:5]1[CH:6]=[C:7]2[C:13]([CH2:14][C:15]3[C:16]([F:32])=[N:17][C:18]([NH:21][CH2:22][C:23]4[C:24]([O:30][CH3:31])=[N:25][CH:26]=[C:27]([F:29])[CH:28]=4)=[CH:19][CH:20]=3)=[CH:12][NH:11][C:8]2=[N:9][CH:10]=1)=[O:2]

Participants

3

Reactant 2

HCID 6329Methylamine2×HCID 671996223-{2-Fluoro-6-[(5-fluoro-2-methoxy-pyridin-3-ylmethyl)-amino]-pyridin-3-ylmethyl}-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid methyl ester

Product 1

HCID 671977913-{2-fluoro-6-[(5-fluoro-2-methoxy-pyridin-3-ylmethyl)-amino]-pyridin-3-ylmethyl}-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid methylamide

Conditions

Temperature
50 °C

Procedure

3-{2-Fluoro-6-[(5-fluoro-2-methoxy-pyridin-3-ylmethyl)-amino]-pyridin-3-ylmethyl}-1H-pyrrolo[2,3-b]pyridine-5-carboxylic acid methyl ester (P-1693, 1 equivalent) is slurried with methylamine (2N in methanol, 15 equivalents) in a sealable vial, sealed and heated at 50° C. overnight. Additional methylamine (2N in methanol, 15 equivalents) is added and heated at 50° C. overnight. The reaction is concentrated under vacuum, the residue dissolved in tetrahydrofuran for purification on a C18 reverse phase column, eluting with 0-100% methanol (with 10% tetrahydrofuran)/water. Appropriated fractions are combined and concentrated under vacuum. The resulting material is triturated with ethyl acetate/heptane and filtered, washing with heptane. The solid is dried under vacuum to provide the desired compound.

Workup

  1. customsealed
  2. temperatureheated at 50° C. overnight
  3. concentrationThe reaction is concentrated under vacuum
  4. dissolutionthe residue dissolved in tetrahydrofuran for purification on a C18 reverse phase column
  5. washeluting with 0-100% methanol (with 10% tetrahydrofuran)/water
  6. concentrationconcentrated under vacuum
  7. customThe resulting material is triturated with ethyl acetate/heptane
  8. filtrationfiltered
  9. washwashing with heptane
  10. customThe solid is dried under vacuum

Sources & evidence

ORD record
ord-2f1bf39a40414efdb6a19c99dc45e828
Source dataset
uspto-grants-2015_08
Patent number
US09096593B2

Reaction notes

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