1,4-Dioxane → Methyl 4-(6-pyridin-3-ylpyrazolo[1,5-c]pyrimidin-3-yl)thiophene-2-carboxylate

HRID 1255859Notes

Reaction equation

HRID 1255859 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]([C:14]([O:16][CH3:17])=[O:15])[S:12][CH:13]=2)O1.Br[C:20]1[CH:21]=[N:22][N:23]2[CH:28]=[C:27](C3C=NC=CC=3)[CH:26]=[N:25][C:24]=12.C(=O)(O)[O-].[Na+].O1[CH2:45][CH2:44]OCC1>>[N:22]1[CH:45]=[CH:44][CH:24]=[C:20]([N:25]2[CH:26]=[CH:27][C:28]3=[C:20]([C:9]4[CH:10]=[C:11]([C:14]([O:16][CH3:17])=[O:15])[S:12][CH:13]=4)[CH:21]=[N:22][N:23]3[CH2:24]2)[CH:21]=1

Participants

5

Reactant 4

HCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 52911233Methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carboxylateHCID 687770603-Bromo-6-pyridin-3-ylpyrazolo[1,5-a]pyrimidine

Product 1

HCID 68775345Methyl 4-(6-pyridin-3-ylpyrazolo[1,5-c]pyrimidin-3-yl)thiophene-2-carboxylate

Conditions

Temperature
85 °C

Procedure

A solution of methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carboxylate (1.09 g, 4.1 mmol) and 3-bromo-6-pyridin-3-ylpyrazolo[1,5-a]pyrimidine (1.1 g, 4.1 mmol) in dioxane (20 mL) and 1M aqueous sodium bicarbonate (12.2 mL, 12.2 mmol) was degassed with nitrogen and treated with palladium tetrakistriphenylphosphine (0.24 g, 0.20 mmol) and heated to 85° C. for 16 hours. The reaction was cooled to room temperature and partitioned between water/methylene chloride. The organics were washed with water and brine, dried over sodium sulfate, filtered and evaporated in vacuo. Purification by flash chromatography (1-5% methanol/methylene chloride) gave methyl 4-(6-pyridin-3-ylpyrazolo[1,5-c]pyrimidin-3-yl)thiophene-2-carboxylate. LC-MS SIMS: m/z 337.1 [M+H]+.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. custompartitioned between water/methylene chloride
  3. washThe organics were washed with water and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customPurification by flash chromatography (1-5% methanol/methylene chloride)

Sources & evidence

ORD record
ord-05c14e3c721f47ba83f5e5b536ae1fe4
Source dataset
uspto-grants-2013_06
Patent number
US08461162B2

Reaction notes

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