Cesium fluoride → HCID 25182570, compound

HRID 500737Notes

Reaction equation

HRID 500737 reaction equation
C(OC([N:8]([C:16]1[C:21]([O:22][CH3:23])=[N:20][C:19](B2OC(C)(C)C(C)(C)O2)=[CH:18][N:17]=1)C(OC(C)(C)C)=O)=O)(C)(C)C.[F:33][CH:34]([F:53])[CH2:35][N:36]1[CH:40]=[C:39]([C:41]2[CH:46]=[CH:45][N:44]=[C:43]([NH:47][CH2:48][CH2:49][C:50]#[N:51])[N:42]=2)[C:38](I)=[N:37]1.[F-].[Cs+].[I-]>C(COC)OC>[NH2:8][C:16]1[N:17]=[CH:18][C:19]([C:38]2[C:39]([C:41]3[CH:46]=[CH:45][N:44]=[C:43]([NH:47][CH2:48][CH2:49][C:50]#[N:51])[N:42]=3)=[CH:40][N:36]([CH2:35][CH:34]([F:53])[F:33])[N:37]=2)=[N:20][C:21]=1[O:22][CH3:23]

Participants

6

Reactant 4

HCID 25953Cesium fluorideHCID 30165Iodide IonHCID 57856249HCID 57856249, compoundHCID 57856300HCID 57856300, compound

Product 1

HCID 25182570HCID 25182570, compound

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of the crude di-tert-butyl[3-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazin-2-yl]imidodicarbonate B-79-3 (0.6 mmol) in dimethoxyethane (2.5 mL) was added 3-{4-[1-(2,2-Difluoro-ethyl)-3-iodo-1H-pyrazol-4-yl]-pyrimidin-2-ylamino}-propionitrile B-33-3 (150 mg, 0.37 mmol) and Cesium Fluoride (1.1 mL of a 1M aqueous solution, 1.1 mmol). The resulting mixture was deoxygenated with a nitrogen bubbler for 5 min and then 1,1′-Bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (15 mg, 0.019 mmol) was added. The mixture was then heated in an 80° C. oil bath for 20 hours. LCMS indicated the iodide had been completely consumed. The mixture was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate. The combined organics were dried over magnesium sulfate and reduced to minimum volume. The residue was taken up in dimethoxyethane (3 mL) and then heated at 170° C. in the microwave for 25 minutes to thermolyze the tert-butoxycarbonyl groups. The resulting dark mixture was filtered through a 0.45μ filter and the filtrate reduced to minimum volume. The residue was purified by HPLC to give 59 mg (37%) of B-79 as a fluffy white solid after lyophilization of the desired fractions. 1H NMR (400 MHz, ACETONITRILE-d3) δ ppm 8.17 (s, 1H), 8.15 (d, J=5.05 Hz, 1H), 7.83 (s, 1H), 6.72 (d, J=5.31 Hz, 1H), 6.27 (tt, J=54.98, 3.76 Hz, 1H), 5.91 (br.t, J=5.18 Hz, 1H), 5.34 (br. s., 2H), 4.59 (td, J=14.65, 3.79 Hz, 2H), 3.76 (s, 3H), 3.55 (q, J=6.23 Hz, 2H), 2.64 (t, J=6.44 Hz, 2H)

Workup

  1. customThe resulting mixture was deoxygenated with a nitrogen bubbler for 5 min
  2. addition1,1′-Bis(diphenylphosphino)ferrocene-palladium(II) dichloride dichloromethane complex (15 mg, 0.019 mmol) was added
  3. customhad been completely consumed
  4. customThe mixture was partitioned between ethyl acetate and water
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. dry with materialThe combined organics were dried over magnesium sulfate
  7. temperatureheated at 170° C. in the microwave for 25 minutes
  8. filtrationThe resulting dark mixture was filtered through
  9. filtrationa 0.45μ filter
  10. customThe residue was purified by HPLC
  11. customto give 59 mg (37%) of B-79 as a fluffy white solid after lyophilization of the desired fractions

Sources & evidence

ORD record
ord-68cc65dea29141e3bc635f467cf163df
Source dataset
uspto-grants-2010_08
Patent number
US07772246B2

Reaction notes

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