Triethylamine → (S)-2-((5-cyano-3-fluoro-6-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)amino)-3,3-dimethylbutyl methanesulfonate

HRID 2171881Notes

Reaction equation

HRID 2171881 reaction equation
[F:1][C:2]1[C:3]([NH:30][C@@H:31]([C:34]([CH3:37])([CH3:36])[CH3:35])[CH2:32][OH:33])=[N:4][C:5]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[C:16]([F:19])[CH:17]=3)[N:12]([S:20]([C:23]3[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=3)(=[O:22])=[O:21])[CH:11]=2)=[C:6]([CH:9]=1)[C:7]#[N:8].C(N(CC)CC)C.[CH3:45][S:46](Cl)(=[O:48])=[O:47]>ClCCl>[CH3:45][S:46]([O:33][CH2:32][C@@H:31]([NH:30][C:3]1[C:2]([F:1])=[CH:9][C:6]([C:7]#[N:8])=[C:5]([C:10]2[C:18]3[C:13](=[N:14][CH:15]=[C:16]([F:19])[CH:17]=3)[N:12]([S:20]([C:23]3[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=3)(=[O:21])=[O:22])[CH:11]=2)[N:4]=1)[C:34]([CH3:37])([CH3:36])[CH3:35])(=[O:48])=[O:47]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 71247622(S)-5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-6-((1-hydroxy-3,3-dimethylbutan-2-yl)amino)nicotinonitrile2×

Product 1

HCID 86714761(S)-2-((5-cyano-3-fluoro-6-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)amino)-3,3-dimethylbutyl methanesulfonate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a cold (0° C.) solution of (S)-5-fluoro-2-(5-fluoro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-6-((1-hydroxy-3,3-dimethylbutan-2-yl)amino)nicotinonitrile, 98a, (3.77 g, 7.17 mmol) and triethylamine (1.25 mL, 8.96 mmol) in dichloromethane (75 mL) was added methanesulfonyl chloride (0.69 mL, 8.96 mmol). The solution was stirred at room temperature for 1 hour. The solvent was removed under reduced pressure and water (100 mL) and EtOAc (200 mL) were added. The organic phase was separated, dried (MgSO4), filtered and concentrated under reduced pressure to afford 4.22 g of the desired product as a yellow foamy solid that was used without further purification: LC/MS (60-90% ACN/water 5 min with 0.9% FA, C4) m/z 604.45 (M+H) retention time=2.03 minutes.

Workup

  1. customThe solvent was removed under reduced pressure and water (100 mL) and EtOAc (200 mL)
  2. additionwere added
  3. customThe organic phase was separated
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1e12ce95a1fd4dfe9e96709283ef5961
Source dataset
uspto-grants-2015_06
Patent number
US09051319B2

Reaction notes

Loading…