Dimethylformamide → benzyl 1-benzyl-6-[4-fluoro-3-(methoxycarbonyl)phenyl]-1H-pyrazolo[3,4-b]pyridine-4-carboxylate

HRID 574994Notes

Reaction equation

HRID 574994 reaction equation
[CH2:1]([N:8]1[C:12]2[N:13]=[C:14](Cl)[CH:15]=[C:16]([C:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])[C:11]=2[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:28][C:29]1(C(OC)=O)[CH:34]=[CH:33][CH:32]=[C:31](B(O)O)[CH2:30]1.[C:42](=[O:45])([O-])[O-:43].[Cs+].[Cs+].[CH3:48]N(C=O)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([N:8]1[C:12]2[N:13]=[C:14]([C:32]3[CH:33]=[CH:34][C:29]([F:28])=[C:30]([C:42]([O:43][CH3:48])=[O:45])[CH:31]=3)[CH:15]=[C:16]([C:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])[C:11]=2[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 896560783-Fluoro-3-methoxycarbonylphenylboronic acidHCID 117778156benzyl 1-benzyl-6-chloro-1H-pyrazolo[3,4-b]pyridine-4-carboxylate

Product 1

HCID 117777954benzyl 1-benzyl-6-[4-fluoro-3-(methoxycarbonyl)phenyl]-1H-pyrazolo[3,4-b]pyridine-4-carboxylateYield 62%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

The catalyst Pd(t-BuP)2 (2.03, 3.97 mmol) or Pd(PPh3)4 (4.58 g/4.0 mmol) is added to a suspension of benzyl 1-benzyl-6-chloro-1H-pyrazolo[3,4-b]pyridine-4-carboxylate (15.0 g/40 mol), 3-fluoro-3-methoxycarbonylphenylboronic acid (15.7 g/79 mol) and caesium carbonate (25.9 g/0.079 mol) in 125 mL of anhydrous DMF under argon. The mixture is stirred at 80° C. for 2 hours under argon. The reaction mixture is hot-filtered through talc, run into a saturated aqueous solution of NaHCO3 and extracted with EtOAc. After separation of the two phases, the organic phase is washed with water, dried over sodium sulphate and then concentrated until the first crystals appear. The crystalline product is filtered, washed with diisopropyl ether, and then dried under vacuum. The filtrate is run into a DCM/cyclohexane (50/50) mixture and the precipitate obtained is filtered and dried under vacuum. The two batches are combined to give 12.3 g of a yellow powder (yield: 62%).

Workup

  1. filtrationThe reaction mixture is hot-filtered through talc
  2. extractionextracted with EtOAc
  3. customAfter separation of the two phases
  4. washthe organic phase is washed with water
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated until the first crystals
  7. filtrationThe crystalline product is filtered
  8. washwashed with diisopropyl ether
  9. customdried under vacuum
  10. customthe precipitate obtained
  11. filtrationis filtered
  12. customdried under vacuum

Sources & evidence

ORD record
ord-1c1d553536434089b0be7a390f71afe5
Source dataset
uspto-grants-2015_05
Patent number
US09034898B2

Reaction notes

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