Ammonium Chloride → 7-Bromo-3-chloro-1-fluorospiro[chromeno[2,3-c]pyridine-5,7'-pyrrolo[3,4-b]pyridin]-5'-amine

HRID 1409514Notes

Reaction equation

HRID 1409514 reaction equation
C([Li])CCC.Br[C:7]1[N:14]=[CH:13][CH:12]=[CH:11][C:8]=1[C:9]#[N:10].[Br:15][C:16]1[CH:17]=[C:18]2[C:29](=[CH:30][CH:31]=1)[O:28][C:21]1[C:22]([F:27])=[N:23][C:24]([Cl:26])=[CH:25][C:20]=1[C:19]2=[N:32]S(C(C)(C)C)=O.[NH4+].[Cl-]>C1COCC1.CCOC(C)=O>[Br:15][C:16]1[CH:17]=[C:18]2[C:19]3([C:7]4=[N:14][CH:13]=[CH:12][CH:11]=[C:8]4[C:9]([NH2:10])=[N:32]3)[C:20]3[CH:25]=[C:24]([Cl:26])[N:23]=[C:22]([F:27])[C:21]=3[O:28][C:29]2=[CH:30][CH:31]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 8171532-Bromopyridine-3-carbonitrileHCID 86658361N-(7-bromo-3-chloro-1-fluoro-5H-chromeno[2,3-c]pyridin-5-ylidene)-2-methylpropane-2-sulfinamideHCID 178418339Butyllithium

Product 1

HCID 866892527-Bromo-3-chloro-1-fluorospiro[chromeno[2,3-c]pyridine-5,7'-pyrrolo[3,4-b]pyridin]-5'-amine

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A solution of n-butyllithium (102 μL, 0.164 mmol, Aldrich) was added dropwise to a solution of 2-bromonicotinonitrile (30 mg, 0.164 mmol, Aldrich) in THF (2 mL) at −95° C. under N2 atmosphere. After 1 min a solution of N-(7-bromo-3-chloro-1-fluoro-5H-chromeno[2,3-c]pyridin-5-ylidene)-2-methylpropane-2-sulfinamide (55 mg, 0.127 mmol, example 1b) in THF (1 mL) was added. After 2 min aqueous, saturated NH4Cl solution was added and the reaction mixture was allowed to warm to RT. EtOAc was added and the organic phase was separated. The organic phase was dried over MgSO4 and the solvent was removed under reduced pressure. The remaining residue was purified by reversed-phase preparative HPLC using a Phenomenex Gemini column, 10 micron, C18, 110 Å, 100×50 mm, 0.1% TFA in CH3CN/H2O, gradient 10% to 100% over 20 min to obtain the title compound as a light-yellow solid. MS m/z=432.8 [M+H]+. Calculated for C18H9BrClFN4O: 431.65

Workup

  1. customthe organic phase was separated
  2. dry with materialThe organic phase was dried over MgSO4
  3. customthe solvent was removed under reduced pressure
  4. customThe remaining residue was purified by reversed-phase preparative HPLC
  5. customover 20 min

Sources & evidence

ORD record
ord-fb8b9a4d7e644fb1b248641904f4798f
Source dataset
uspto-grants-2014_12
Patent number
US08921363B2

Reaction notes

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