Sodium hydride → N'-[5-(6-chloro-3-cyano-1-methyl-1H-indol-2-yl)-pyridin-3-yl]-N,N-dimethyl-formamidine

HRID 593676Notes

Reaction equation

HRID 593676 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]([CH3:20])[C:10]3[C:15]([C:16]=2[C:17]#[N:18])=[CH:14][CH:13]=[C:12]([Cl:19])[CH:11]=3)[CH:5]=[N:6][CH:7]=1.[H-].[Na+].CC(S(Cl)(=O)=O)C>CN(C=O)C>[Cl:19][C:12]1[CH:11]=[C:10]2[C:15]([C:16]([C:17]#[N:18])=[C:8]([C:4]3[CH:3]=[C:2]([N:1]=[CH:8][N:9]([CH3:20])[CH3:10])[CH:7]=[N:6][CH:5]=3)[N:9]2[CH3:20])=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 824082-Propanesulfonyl chlorideHCID 582156042-(5-amino-pyridin-3-yl)-6-chloro-1-methyl-1H-indole-3-carbonitrile

Product 1

HCID 58215796N'-[5-(6-chloro-3-cyano-1-methyl-1H-indol-2-yl)-pyridin-3-yl]-N,N-dimethyl-formamidine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(5-amino-pyridin-3-yl)-6-chloro-1-methyl-1H-indole-3-carbonitrile (Example 211, 85 mg, 0.3 mmol) in DMF (5 mL) is added 60% NaH in mineral oil (48 mg, 1.2 mmol), followed with propane-2-sulfonyl chloride (86 mg, 60.6 mmol). The mixture is stirred at room temperature for 5 h. The mixture is filtered and the filtrate is purified on Xbridge C18 eluting with a 1:9 to 9:1 acetonitrile-water gradient to give N′-[5-(6-chloro-3-cyano-1-methyl-1H-indol-2-yl)-pyridin-3-yl]-N,N-dimethyl-formamidine. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.98 (s, 3H), 3.06 (s, 3H), 3.79 (s, 3H), 7.35 (dd, J=8.3, 1.8 Hz, 1H), 7.62 (t, J=2.1 Hz, 1H), 7.70 (d, J=8.3 Hz, 1H), 7.95 (d, J=1.8 Hz, 1H), 7.96 (s, 1H), 8.37-8.39 (m, 2H). HRMS (ESI) m/z 338.1182 [(M+H)+ Calcd for C18H17ClN5: 338.1173].

Workup

  1. filtrationThe mixture is filtered
  2. customthe filtrate is purified on Xbridge
  3. washC18 eluting with a 1:9 to 9:1 acetonitrile-water gradient

Sources & evidence

ORD record
ord-1ea5b7f33b294016ad68b49eb391fc65
Source dataset
uspto-grants-2016_01
Patent number
US09242963B2

Reaction notes

Loading…