Cesium carbonate → HCID 178510056, compound

HRID 505572Notes

Reaction equation

HRID 505572 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]2[NH:6][N:7]=[N:8][C:4]=2[C:3]=1[O:11][C:12]1[CH:13]=[C:14]([C:20]#[N:21])[CH:15]=[C:16]([CH:19]=1)[C:17]#[N:18].ClC1C=C(C=C(OC2C3N=NNC=3C=CC=2Cl)C=1)C#N.Br[CH2:43][C:44]1[C:52]2[C:47](=[N:48][CH:49]=[CH:50][CH:51]=2)[N:46](C(OC(C)(C)C)=O)[N:45]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]2[N:6]([CH2:43][C:44]3[C:52]4[C:47](=[N:48][CH:49]=[CH:50][CH:51]=4)[NH:46][N:45]=3)[N:7]=[N:8][C:4]=2[C:3]=1[O:11][C:12]1[CH:13]=[C:14]([C:20]#[N:21])[CH:15]=[C:16]([CH:19]=1)[C:17]#[N:18]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 10828872tert-Butyl 3-(bromomethyl)-1H-pyrazolo[3,4-b]pyridine-1-carboxylate2×HCID 178509930HCID 178509930, compoundHCID 178510057HCID 178510057, compound

Product 1

HCID 178510056HCID 178510056, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A partially purified product prepared in the manner described in Example 4A, step 5, except on a larger scale, was found to contain approximately 10 mol % 5-[(5-chloro-1H-1,2,3-benzotriazol-4-yl)oxy]isophthalonitrile in addition to 3-chloro-5-[(5-chloro-1H-1,2,3-benzotriazol-4-yl)oxy]benzonitrile. A solution of tert-butyl 3-(bromomethyl)-1H-pyrazolo[3,4-b]pyridine-1-carboxylate (Intermediate 1; 23 g, 74 mmol) in DMF (100 mL) was added to a suspension of the partially purified product (25 g, 82 mmol) and cesium carbonate (28 g, 86 mmol) in DMF (80 mL) at room temperature, and the resulting mixture was stirred for 1 hour at room temperature. The reaction mixture was then quenched with aqueous saturated ammonium chloride (200 mL), diluted with water (100 mL) and extracted with ethyl acetate (2×700 mL). The combined organic fractions were washed with dilute brine (3×500 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The resulting residue was adsorbed onto silica gel and subjected to automated silica gel chromatography eluting with a gradient of 25-50% ethyl acetate in hexanes to afford the crude title product. This mixture was then purified by reverse phase column chromatography eluting with 5-95% CH3CN/H2O (0.1% TFA) to yield the title compound. 1H NMR (DMSO-d6) δ 8.53 (dd, J=4.6 Hz, J=1.5 Hz, 1H), 8.22 (m, 1H), 8.15 (dd, J=8.2 Hz, J=1.5 Hz, 1H), 8.00 (m, 2H), 7.92 (d, J=8.9 Hz, 1H), 7.78 (d, J=8.9 Hz, 1H), 7.21 (dd, J=8.0 Hz, J=4.5 Hz, 1H), 6.39 (s, 2H). LRMS (M+1)=426.9.

Workup

  1. customA partially purified product prepared in the manner
  2. customThe reaction mixture was then quenched with aqueous saturated ammonium chloride (200 mL)
  3. additiondiluted with water (100 mL)
  4. extractionextracted with ethyl acetate (2×700 mL)
  5. washThe combined organic fractions were washed with dilute brine (3×500 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. washeluting with a gradient of 25-50% ethyl acetate in hexanes
  10. customto afford the crude title product
  11. customThis mixture was then purified by reverse phase column chromatography
  12. washeluting with 5-95% CH3CN/H2O (0.1% TFA)

Sources & evidence

ORD record
ord-4c2b5438e8594fd483e24729e27d5e02
Source dataset
uspto-grants-2010_08
Patent number
US07781454B2

Reaction notes

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