Cesium carbonate → HCID 22220908, compound

HRID 1794294Notes

Reaction equation

HRID 1794294 reaction equation
CC1(C)COB([C:8]2[CH:16]=[C:15]3[C:11]([CH2:12][N:13]4[C:19]([C:20]5[C:21]([C:26]6[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=6)=[N:22][O:23][C:24]=5[CH3:25])=[N:18][N:17]=[C:14]43)=[CH:10][CH:9]=2)OC1.Cl[C:34]1[N:39]=[C:38]([C:40]([O:42]C)=[O:41])[CH:37]=[N:36][CH:35]=1.C([O-])([O-])=O.[Cs+].[Cs+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCOCC1>[CH3:25][C:24]1[O:23][N:22]=[C:21]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:20]=1[C:19]1[N:13]2[CH2:12][C:11]3[C:15]([C:14]2=[N:17][N:18]=1)=[CH:16][C:8]([C:34]1[N:39]=[C:38]([C:40]([OH:42])=[O:41])[CH:37]=[N:36][CH:35]=1)=[CH:9][CH:10]=3

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 11084353Methyl 6-chloropyrazine-2-carboxylateHCID 69895651HCID 69895651, compound

Product 1

HCID 22220908HCID 22220908, compoundYield 35.5%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 8-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)-3-(5-methyl-3-phenylisoxazol-4-yl)-5H-[1,2,4]triazolo[3,4-α]isoindole (248 mg, 0.58 mmol) (as prepared in Example 26 Step (a)), methyl 6-chloropyrazine-2-carboxylate (100 mg, 0.58 mmol), dioxane (4.8 ml) and 2M aqueous Cs2CO3 solution (0.58 ml) was degassed with a stream of N2 for 10 min. Bis(triphenylphosphine)palladium dichloride (12 mg, 0.22 μmol) was added and the stirred mixture was heated at reflux for 1.5 h. The reaction was then cooled, allowed to stand for 15 min and the supernatent decanted off. The remaining salts were washed with further dioxane (5 ml) and then partitioned between water (20 ml) and CH2Cl2 (20 ml). The pH was adjusted to 6 by dropwise addition of 2N aqueous HCl and the aqueous phase was extracted with further CH2Cl2 (2×20 ml). The combined organic extracts were dried over Na2SO4 and concentrated in vacuo to yield the title compound as a white amorphous solid (89.8 mg, 34%); 1H NMR (400 MHz, CDCl3) δ 9.63 (1H, s), 9.19 (1H, s), 8.81 (1H, s), 8.38 (1H, dd, J=8.2, 1.7 Hz), 7.75 (1H, d, J=8.2 Hz), 7.56–7.48 (5H, m), 4.67 (2H, s), 2.64 (3H, s); m/z (ES+) 437 (M+H)+.

Workup

  1. customwas degassed with a stream of N2 for 10 min
  2. temperaturethe stirred mixture was heated
  3. temperatureat reflux for 1.5 h
  4. temperatureThe reaction was then cooled
  5. customthe supernatent decanted off
  6. washThe remaining salts were washed with further dioxane (5 ml)
  7. custompartitioned between water (20 ml) and CH2Cl2 (20 ml)
  8. additionThe pH was adjusted to 6 by dropwise addition of 2N aqueous HCl
  9. extractionthe aqueous phase was extracted with further CH2Cl2 (2×20 ml)
  10. dry with materialThe combined organic extracts were dried over Na2SO4
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-198e7ca25aa24981840bdb4ff8f2dff8
Source dataset
uspto-grants-2006_04
Patent number
US07022724B2

Reaction notes

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