Sodium Hydroxide → [6-fluoro-5-(5-methanesulfonyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(5-fluoro-2-methoxy-pyridin-3-ylmethyl)-amine

HRID 510012Notes

Reaction equation

HRID 510012 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([CH2:11][C:12]3[CH:13]=[CH:14][C:15]([NH:19][CH2:20][C:21]4[C:22]([O:28][CH3:29])=[N:23][CH:24]=[C:25]([F:27])[CH:26]=4)=[N:16][C:17]=3[F:18])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.N1CCC[C@H]1C(O)=O.[CH3:38][S:39]([O-:41])=[O:40].[Na+].[OH-].[Na+]>CS(C)=O.[Cl-].[Na+].O.[Cu]I.C(OCC)(=O)C>[F:18][C:17]1[N:16]=[C:15]([NH:19][CH2:20][C:21]2[C:22]([O:28][CH3:29])=[N:23][CH:24]=[C:25]([F:27])[CH:26]=2)[CH:14]=[CH:13][C:12]=1[CH2:11][C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([S:39]([CH3:38])(=[O:41])=[O:40])[CH:3]=2)[NH:8][CH:9]=1

Participants

9

Reactant 4

HCID 14798Sodium Hydroxide2×HCID 145742L-Proline2×HCID 2733271Sodium methanesulfinate2×HCID 58259257[5-(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-6-fluoro-pyridin-2-yl]-(5-fluoro-2-methoxy-pyridin-3-ylmethyl)-amine

Product 1

HCID 67199470[6-fluoro-5-(5-methanesulfonyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(5-fluoro-2-methoxy-pyridin-3-ylmethyl)-amine

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
100 °C

Procedure

[5-(5-Bromo-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-6-fluoro-pyridin-2-yl]-(5-fluoro-2-methoxy-pyridin-3-ylmethyl)-amine (P-1497, 1 equivalent) is dissolved in 5 mL of dimethyl sulfoxide in a sealable vial. Copper(I) iodide (0.2 equivalent), L-proline (0.2 equivalent), sodium methanesulfinate (175, 1.2 equivalents), and sodium hydroxide (0.2 equivalent) are added. The vial is sealed and heated at 100° C. overnight, then additional copper(I) iodide (0.2 equivalent), L-proline (0.2 equivalent), sodium methanesulfinate (1.2 equivalent), and sodium hydroxide (0.2 equivalent) are added, and the reaction is sealed and heated at 120° C. overnight. The reaction is added to ethyl acetate and brine and extracted. The organic layer is concentrated under vacuum and the resulting material dissolved in tetrahydrofuran for purification on a C18 reverse phase column, eluting with 0-100% methanol (with 10% tetrahydrofuran)/water. Appropriate fractions are combined and concentrated under vacuum. The resulting material is triturated with methyl tert-butyl ether and filtered, washing with methyl tert-butyl ether, then heptane. The solid is dried under vacuum to provide the desired compound.

Workup

  1. customThe vial is sealed
  2. customthe reaction is sealed
  3. temperatureheated at 120° C. overnight
  4. extractionextracted
  5. concentrationThe organic layer is concentrated under vacuum
  6. dissolutionthe resulting material dissolved in tetrahydrofuran for purification on a C18 reverse phase column
  7. washeluting with 0-100% methanol (with 10% tetrahydrofuran)/water
  8. concentrationconcentrated under vacuum
  9. customThe resulting material is triturated with methyl tert-butyl ether
  10. filtrationfiltered
  11. washwashing with methyl tert-butyl ether
  12. customThe solid is dried under vacuum

Sources & evidence

ORD record
ord-826365ef9e8c4e1183e37289fd14f43a
Source dataset
uspto-grants-2015_08
Patent number
US09096593B2

Reaction notes

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