Potassium Carbonate → HCID 178452731, compound

HRID 1641309Notes

Reaction equation

HRID 1641309 reaction equation
Cl.Cl.[CH:3]1([NH2+:9][C:10]2[C:14]3([CH2:19][CH2:18][NH2+:17][CH2:16][CH2:15]3)[N:13]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=3)[C:12](=[O:27])[N:11]=2)[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.Br[CH2:29][C:30]1[CH:31]=[CH:32][C:33]([NH:36][C:37](=[O:43])[O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[N:34][CH:35]=1.N1C(C)=CC=CC=1C.[Li+].[Br-].C1COCC1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[CH:3]1([NH:9][C:10]2[C:14]3([CH2:15][CH2:16][N:17]([CH2:29][C:30]4[CH:31]=[CH:32][C:33]([NH:36][C:37](=[O:43])[O:38][C:39]([CH3:41])([CH3:40])[CH3:42])=[N:34][CH:35]=4)[CH2:18][CH2:19]3)[N:13]([C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[CH:21]=3)[C:12](=[O:27])[N:11]=2)[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 23030321tert-Butyl (5-(bromomethyl)pyridin-2-yl)carbamateHCID 866146104-(Cyclohexylammonio)-1-(3-fluorophenyl)-2-oxo-1,3-diaza-8-azoniaspiro[4.5]dec-3-ene dihydrochlorideHCID 131729445lutidine LiBr THF

Product 1

HCID 178452731HCID 178452731, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

To a solution of 188 mg (0.45 mmol) 4-(cyclohexylammonio)-1-(3-fluorophenyl)-2-oxo-1,3-diaza-8-azoniaspiro[4.5]dec-3-ene dihydrochloride (5-2) and 136 mg (0.473 mmol) tert-butyl 5-(bromomethyl)pyridin-2-ylcarbamate (prepared in a manner similar to that described in PCT application WO 00/0665570, substituting Methanesulfonicanhydredl/lutidine/LiBr/THF 0-55° C. in the bromination step) in 2.5 mL DMF was added 399 mg (2.89 mmol) granular potassium carbonate and the mixture stirred vigorously at 55° C. overnight. The reaction mixture was treated with 30 mL H2O and extracted with EtOAc (3×25 mL). The combined extracts were washed with H2O (1×20 mL), brine (1×20 mL), dried over Na2SO4, filtered, and concentrated to dryness in vacuo to give a crude oily solid (390 mg). Purification by automated flash chromatography (0-6% MeOH in CH2Cl2 over 20 m) afforded tert-butyl 5-{[4-(cyclohexylamino)-1-(3-fluorophenyl)-2-oxo-1,3,8-triazaspiro[4.5]dec-3-en-8-yl]methyl}pyridin-2-ylcarbamate as a white solid. 1H NMR (DMSO, 400 MHz): δ 9.67 (s, 1H), 8.09 (d, J=7.78 Hz, 1H), 7.97 (s, 1H), 7.69 (d, J=8.42 Hz 1H), 7.46 (dd, J=8.52, 2.10 Hz 1H), 7.36 (m, 1H), 7.14 (m, 2H), 7.07 (d, J=8.15 Hz 1H), 3.68 (m, 1H), 3.22 (s, 2H), 2.53 (m, 2H), 2.09 (m, 2H), 1.82 (m, 4H), 1.73 (m, 1H), 1.61 (m, 1H), 1.47 (s, 9H), 1.29 (m, 5H), 1.12 (m, 1H). High resolution mass spec (FT/ICR): calc M+H=551.3141. found 551.3157

Workup

  1. extractionextracted with EtOAc (3×25 mL)
  2. washThe combined extracts were washed with H2O (1×20 mL), brine (1×20 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated to dryness in vacuo
  6. customto give a crude oily solid (390 mg)
  7. customPurification by automated flash chromatography (0-6% MeOH in CH2Cl2 over 20 m)

Sources & evidence

ORD record
ord-39001f99e37441118242aa5a83064aed
Source dataset
uspto-grants-2012_02
Patent number
US08114887B2

Reaction notes

Loading…