Cesium carbonate → HCID 59053727, compound

HRID 1748202Notes

Reaction equation

HRID 1748202 reaction equation
[CH:1]12[NH:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][CH:3]([O:9][CH2:10][C:11]1[C:12]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[O:25][C:26]([F:29])([F:28])[F:27])=[N:13][O:14][C:15]=1[CH:16]1[CH2:18][CH2:17]1)[CH2:2]2.CN(C)C(=O)C.C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:43]1[S:44][C:45]2[CH:51]=[C:50]([C:52]([O:54][CH3:55])=[O:53])[CH:49]=[C:48]([F:56])[C:46]=2[N:47]=1>C(OCC)(=O)C>[CH:16]1([C:15]2[O:14][N:13]=[C:12]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[O:25][C:26]([F:28])([F:27])[F:29])[C:11]=2[CH2:10][O:9][CH:3]2[CH2:2][CH:1]3[N:8]([C:43]4[S:44][C:45]5[CH:51]=[C:50]([C:52]([O:54][CH3:55])=[O:53])[CH:49]=[C:48]([F:56])[C:46]=5[N:47]=4)[CH:5]([CH2:6][CH2:7]3)[CH2:4]2)[CH2:17][CH2:18]1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 31374DimethylacetamideHCID 57527206HCID 57527206, compoundHCID 67983256HCID 67983256, compound

Product 1

HCID 59053727HCID 59053727, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Into a 25-mL round-bottom flask equipped with a stir bar was added sequentially 4-((8-azabicyclo[3.2.1]octan-3-yloxy)methyl)-5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazole (I-1H) (0.525 g, 1.29 mmol), 3.6 mL of N,N-dimethylacetamide, cesium carbonate (1.08 g, 3.31 mmol), and methyl 2-bromo-4-fluorobenzo[d]thiazole-6-carboxylate (1.12 g, 3.87 mmoles). After stirring the resulting slurry at room temperature for 10 minutes, the mixture was then warmed to 60° C. and stirred for 1 h. The reaction slurry was allowed to cool to RT, and was diluted with 200 mL of ethyl acetate and washed with water (3×30 mL). The organic extracts were concentrated under vacuum and directly purified using normal phase silica gel chromatography (40 g silica column) with a 15 min gradient of 10% to 60% ethyl acetate/hexanes. Desired fractions were concentrated in vacuo, and the resulting residue crystallized upon standing to give the desired product as a white crystalline solid.

Workup

  1. customInto a 25-mL round-bottom flask equipped with a stir bar
  2. temperaturethe mixture was then warmed to 60° C.
  3. stirringstirred for 1 h
  4. temperatureto cool to RT
  5. washwashed with water (3×30 mL)
  6. concentrationThe organic extracts were concentrated under vacuum
  7. customdirectly purified
  8. customwith a 15 min
  9. concentrationDesired fractions were concentrated in vacuo
  10. customthe resulting residue crystallized

Sources & evidence

ORD record
ord-88bb911340de485698594a729dc5db2e
Source dataset
uspto-grants-2015_10
Patent number
US09150568B2

Reaction notes

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