Ethyl Acetate → HCID 136402450, compound

HRID 548375Notes

Reaction equation

HRID 548375 reaction equation
Br[C:2]1[CH:34]=[N:33][C:5]2[NH:6][C:7]([C:12]3[C:13](=[O:32])[N:14]([CH2:24][C:25]4[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=4)[CH:15]4[CH:20]([C:21]=3[OH:22])[CH:19]3[CH2:23][CH:16]4[CH2:17][CH2:18]3)=[N:8][S:9](=[O:11])(=[O:10])[C:4]=2[CH:3]=1.C([O-])=O.[NH4+].C(OCC)(=O)C>CO.[Pd]>[O:11]=[S:9]1(=[O:10])[C:4]2[CH:3]=[CH:2][CH:34]=[N:33][C:5]=2[NH:6][C:7]([C:12]2[C:13](=[O:32])[N:14]([CH2:24][C:25]3[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=3)[C@@H:15]3[C@H:20]([C:21]=2[OH:22])[C@@H:19]2[CH2:23][C@H:16]3[CH2:17][CH2:18]2)=[N:8]1

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 2723923Ammonium formateHCID 136402469HCID 136402469, compound

Product 1

HCID 136402450HCID 136402450, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

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, 0.07 g, 0.128 mmol) was dissolved in methanol (8 mL). Ammonium formate (0.2 g, 3.17 mmol) followed by 10% palladium on carbon (wet, 0.1 g) were added. The mixture stirred at 50° C. for 3 h. The mixture was filtered through Celite and the filtrate was concentrated in vacuo. The residue was dissolved in water (5 mL) and ethyl acetate (50 mL). The mixture was shaken and the layers were separated. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo to a clear oil. Flash column chromatography (Merck silica gel 60, 40-63 μm; 20 to 40% ethyl acetate in hexanes) afforded the desired product, (1R,2S,7R,8S)-5-(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 (0.0441 g, 0.094 mmol, 74%), as a white, brittle foam. 1H NMR (400 MHz, DMSO-d6) δ: 1.11-1.61 (6H, m), 2.51 (1H, s), 2.63 (1H, s), 2.99 (1H, d, J=9.4 Hz), 3.54 (1H, d, J=9.4 Hz), 4.41 (1H, d, J=15.7 Hz), 4.95 (1H, d, J=15.4 Hz), 7.14 (2H, t, J=8.6 Hz), 7.33 (2H, dd, J1=8.6 Hz, J2=5.4 Hz), 7.51 (1H, dd, J1=7.8 Hz, J2=4.5 Hz), 8.34 (1H, d, J=7.6 Hz), 8.68 (1H, dd, J1=4.6 Hz, J2=1.7 Hz). LC-MS (ESI) calcd for C23H21FN4O4S 468.13, found 469.4 [M+H+].

Workup

  1. additionwere added
  2. filtrationThe mixture was filtered through Celite
  3. concentrationthe filtrate was concentrated in vacuo
  4. dissolutionThe residue was dissolved in water (5 mL)
  5. stirringThe mixture was shaken
  6. customthe layers were separated
  7. dry with materialThe organic layer was dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo to a clear oil

Sources & evidence

ORD record
ord-e5457c9bd99a4eeeaa7a8ab7faa9a3c3
Source dataset
uspto-grants-2011_05
Patent number
US07939524B2

Reaction notes

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