Cesium carbonate → HCID 59374057, compound

HRID 473669Notes

Reaction equation

HRID 473669 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[N:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[NH:13][C:14]1[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=1.F[C:22]1[C:27]([CH:28]2[CH2:32][CH2:31][C:30]([CH3:34])([OH:33])[CH2:29]2)=[CH:26][CH:25]=[CH:24][N:23]=1.CN1C(=O)CCC1>C(OCC)(=O)C>[CH3:34][C:30]1([OH:33])[CH2:31][CH2:32][CH:28]([C:27]2[C:22]([O:20][C:17]3[CH:18]=[CH:19][C:14]([NH:13][C:8]4[CH:9]=[CH:10][CH:11]=[CH:12][N:7]=4)=[CH:15][CH:16]=3)=[N:23][CH:24]=[CH:25][CH:26]=2)[CH2:29]1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 13387N-methyl-2-pyrrolidoneHCID 212625714-(Pyridin-2-ylamino)phenolHCID 59326940HCID 59326940, compound

Product 1

HCID 59374057HCID 59374057, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
200 °C

Procedure

To a 20 mL microwave vial was added cesium carbonate (834 mg, 2.56 mmol), 4-(pyridin-2-ylamino)phenol (191 mg, 1.024 mmol), and 3-(2-fluoropyridin-3-yl)-1-methylcyclopentanol (200 mg, 1.024 mmol) followed by NMP (2049 μL). The slurry was heated to 200° C. for 3 h in an Initiator microwave reactor (Personal Chemistry, Biotage AB, Inc., Upssala, Sweden). The reaction mixture was diluted with ethyl acetate (35 mL) and washed with 5N NaOH (5×30 mL) before drying over magnesium sulfate, filtering, and concentrating to a dark orange oil under reduced pressure. The oil was dissolved in 2 mL DMSO and transferred to a preparative HPLC vial through a 0.45 μm syringe filter. The crude compound was purified in three aliquots over 25 minutes per sample (5% 0.1% TFA in ACN:0.1% TFA in water to 80% over 15 minutes with a ten minute hold at 80%) on a Shimadzu Prominence Prep HPLC. The major peaks were collected and diluted with DCM (40 mL) before washed with saturated aqueous sodium bicarbonate (3×40 mL), drying over magnesium sulfate, filtering, and concentrating under reduced pressure, yielding the product as a yellow oil. MS (ESI, pos. ion) m/z: 362.3 (M+1). IC50 (uM) 0.035.

Workup

  1. washwashed with 5N NaOH (5×30 mL)
  2. dry with materialbefore drying over magnesium sulfate
  3. filtrationfiltering
  4. concentrationconcentrating to a dark orange oil under reduced pressure
  5. dissolutionThe oil was dissolved in 2 mL DMSO
  6. filtrationfilter
  7. customThe crude compound was purified in three aliquots over 25 minutes per sample (5% 0.1% TFA in ACN
  8. customThe major peaks were collected
  9. additiondiluted with DCM (40 mL)
  10. washbefore washed with saturated aqueous sodium bicarbonate (3×40 mL)
  11. dry with materialdrying over magnesium sulfate
  12. filtrationfiltering
  13. concentrationconcentrating under reduced pressure

Sources & evidence

ORD record
ord-d07d7c9c9e0045bd944961bf9cf86d33
Source dataset
uspto-grants-2014_01
Patent number
US08637500B2

Reaction notes

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