Potassium Carbonate → 3-(2-(4-(4-cyano-1-methyl-1H-imidazo[4,5-c]pyridin-6-yl)-2-trifluoromethyl-phenoxy)-ethyl)-2,4-dioxo-1,3,8-triaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester

HRID 2079540Notes

Reaction equation

HRID 2079540 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:19][CH2:18][C:11]2([NH:15][C:14](=[O:16])[NH:13][C:12]2=[O:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CS(O[CH2:25][CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]2[N:39]=[C:38]([C:40]#[N:41])[C:37]3[N:42]=[CH:43][N:44]([CH3:45])[C:36]=3[CH:35]=2)=[CH:30][C:29]=1[C:46]([F:49])([F:48])[F:47])(=O)=O.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCCC[N+](CCCC)(CCCC)CCCC.[I-]>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11]2([NH:15][C:14](=[O:16])[N:13]([CH2:25][CH2:26][O:27][C:28]3[CH:33]=[CH:32][C:31]([C:34]4[N:39]=[C:38]([C:40]#[N:41])[C:37]5[N:42]=[CH:43][N:44]([CH3:45])[C:36]=5[CH:35]=4)=[CH:30][C:29]=3[C:46]([F:49])([F:47])[F:48])[C:12]2=[O:17])[CH2:18][CH2:19]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 3629994Tert-butyl 2,4-dioxo-1,3,8-triazaspiro[4.5]decane-8-carboxylateHCID 576575602-(4-(4-cyano-1-methyl-1H-imidazo[4,5-c]pyridin-6-yl)-2-(trifluoromethyl)phenoxy)ethyl methanesulfonate

Product 1

HCID 671005813-(2-(4-(4-cyano-1-methyl-1H-imidazo[4,5-c]pyridin-6-yl)-2-trifluoromethyl-phenoxy)-ethyl)-2,4-dioxo-1,3,8-triaza-spiro[4.5]decane-8-carboxylic acid tert-butyl esterYield 55.8%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
90 °C

Procedure

A solution of 8-tert-butoxycarbonyl-1,3,8-triaza-spiro[4.5]decane-2,4-dione (75 mg) in DMF (1 mL) was added to a solution of 2-(4-(4-cyano-1-methyl-1H-imidazo[4,5-c]pyridin-6-yl)-2-(trifluoromethyl)phenoxy)ethyl methanesulfonate (90 mg) in DMF (1 mL), K2CO3 (83 mg) and TBAI (48 mg). The mixture was stirred overnight at 90° C. The solvent was removed under reduced pressure. The residue was partitioned between ethyl acetate (50 ml) and a saturated solution of Na2CO3 (20 ml). The organic layer was dried over sodium sulphate, filtered and concentrated under reduced pressure to afford 3-(2-(4-(4-cyano-1-methyl-1H-imidazo[4,5-c]pyridin-6-yl)-2-trifluoromethyl-phenoxy)-ethyl)-2,4-dioxo-1,3,8-triaza-spiro[4.5]decane-8-carboxylic acid tert-butyl ester (70 mg). The crude product was dissolved in MeOH (2 mL) and a 5N solution of HCl in iPrOH (0.05 ml) was added. The mixture was stirred 2 hours at 60° C., then the solvent was evaporated under reduced pressure. The crude product was directly purified by preparative HPLC (HPLC:column XBridge MS C18 30×100 mm, 5 μm, Eluent:A:NH4HCO3, 10 mmol, pH=9.5/B:Acetonitrile, Focused gradient/8 minutes/50 mL/min) to afford 6-{4-[2-(2,4-dioxo-1,3,8-triaza-spiro[4.5]dec-3-yl)-ethoxy]-3-(trifluoromethyl)-phenyl}-1-methyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile (23 mg).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customThe residue was partitioned between ethyl acetate (50 ml)
  3. dry with materialThe organic layer was dried over sodium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-d4cff9439f13440790dc8dcb96e116fb
Source dataset
uspto-grants-2011_04
Patent number
US07932251B2

Reaction notes

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