Ammonium Chloride → HCID 136402460, compound

HRID 548374Notes

Reaction equation

HRID 548374 reaction equation
[CH3:1][S:2]([NH2:5])(=[O:4])=[O:3].P([O-])([O-])([O-])=O.[K+].[K+].[K+].N1CCC[C@H]1C(O)=O.Br[C:23]1[CH:55]=[N:54][C:26]2[NH:27][C:28]([C:33]3[C:34](=[O:53])[N:35]([CH2:45][C:46]4[CH:51]=[CH:50][C:49]([F:52])=[CH:48][CH:47]=4)[CH:36]4[CH:41]([C:42]=3[OH:43])[CH:40]3[CH2:44][CH:37]4[CH2:38][CH2:39]3)=[N:29][S:30](=[O:32])(=[O:31])[C:25]=2[CH:24]=1.[Cl-].[NH4+]>CS(C)=O.ClCCl.[Cu](I)I.C(OCC)(=O)C>[F:52][C:49]1[CH:50]=[CH:51][C:46]([CH2:45][N:35]2[C:34](=[O:53])[C:33]([C:28]3[NH:27][C:26]4[N:54]=[CH:55][C:23]([NH:5][S:2]([CH3:1])(=[O:4])=[O:3])=[CH:24][C:25]=4[S:30](=[O:32])(=[O:31])[N:29]=3)=[C:42]([OH:43])[C@H:41]3[C@@H:36]2[C@H:37]2[CH2:44][C@@H:40]3[CH2:39][CH2:38]2)=[CH:47][CH:48]=1

Participants

10

Reactant 5

HCID 25517Ammonium ChlorideHCID 62657Potassium Phosphate, TribasicHCID 72879MethanesulfonamideHCID 145742L-ProlineHCID 136402469HCID 136402469, compound

Product 1

HCID 136402460HCID 136402460, compoundYield 17.5%

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 679Dimethyl SulfoxideSolvent2×HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
110 °C

Procedure

Methane sulfonamide (0.348 g, 3.66 mmol), potassium phosphate (0.078 g, 0.366 mmol), L-proline (0.021 g, 0.183 mmol) and copper iodide (0.035 g, 0.183 mmol) were combined and suspended in dimethylsulfoxide (0.5 mL). The flask was degassed and backfilled with argon. The mixture was heated, while stirring, at 110° C. for 5 min. 5-(7-Bromo-1,1-dioxo-1,4-dihydro-1λ6-pyrido[2,3-e][1,2,4]thiadiazin-3-yl)-3-(4-fluoro-benzyl)-6-hydroxy-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-one (prepared as described in Example 62, 0.1 g, 0.183 mmol) was dissolved in dimethylsulfoxide (0.5 mL) and transferred to the reaction mixture. The mixture was stirred at 110° C. for 16 h. Upon cooling, the mixture was poured into ethyl acetate (150 mL) and saturated aqueous ammonium chloride solution (100 mL). The mixture was shaken and everything was passed through a plug of Celite. The organic layer was separated from the filtrate, washed with saturated aqueous ammonium chloride solution (50 mL), saturated aqueous brine solution (50 mL), dried over magnesium sulfate, filtered and concentrated in vacuo to a brown waxy solid. Flash column chromatography (Merck silica gel 60, 40-63 μm; 0 to 50% ethyl acetate in dichloromethane) afforded the desired product, N-{3-[(1R,2S,7R,8S)-3-(4-fluoro-benzyl)-6-hydroxy-4-oxo-3-aza-tricyclo[6.2.1.02,7]undec-5-en-5-yl]-1,1-dioxo-1,4-dihydro-1λ6-pyrido[2,3-e][1,2,4]thiadiazin-7-yl}-methanesulfonamide (0.018 g, 0.032 mmol, 17.5%), as a beige solid. 1H NMR (400 MHz, DMSO-d6) δ: 1.04-1.52 (6H, m), 2.37-2.41 (1H, m), 2.53-2.56 (1H, m), 3.05 (3H, s), 3.25-3.34 (2H, m), 4.25 (1H, d, J=15.1 Hz), 4.93 (1H, d, J=15.0 Hz), 7.11 (2H, t, J=9.1 Hz), 7.27 (2H, dd, J1=8.7 Hz, J2=5.4 Hz), 7.81 (1H, s), 8.36 (1H, s), 10.01 (1H, bs). LC-MS (ESI) calcd for C24H24FN5O6S2 561.12, found 562.4 [M+H+].

Workup

  1. customThe flask was degassed
  2. temperatureThe mixture was heated
  3. stirringThe mixture was stirred at 110° C. for 16 h
  4. temperatureUpon cooling
  5. stirringThe mixture was shaken
  6. customThe organic layer was separated from the filtrate
  7. washwashed with saturated aqueous ammonium chloride solution (50 mL), saturated aqueous brine solution (50 mL)
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo to a brown waxy solid

Sources & evidence

ORD record
ord-523592ddb51947ef8be8193b5df93989
Source dataset
uspto-grants-2011_05
Patent number
US07939524B2

Reaction notes

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