Water → Methyl 5-{3-(cyanomethyl)-3-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}pyrazine-2-carboxylate

HRID 571550Notes

Reaction equation

HRID 571550 reaction equation
[C:1]([CH2:3][C:4]1([N:18]2[CH:22]=[C:21](B3OC(C)(C)C(C)(C)O3)[CH:20]=[N:19]2)[CH2:7][N:6]([C:8]2[N:9]=[CH:10][C:11]([C:14]([O:16][CH3:17])=[O:15])=[N:12][CH:13]=2)[CH2:5]1)#[N:2].Br[C:33]1[CH:38]=[CH:37][N:36]=[C:35]2[NH:39][CH:40]=[CH:41][C:34]=12.C(=O)(O)[O-].[Na+].O>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.O1CCOCC1>[C:1]([CH2:3][C:4]1([N:18]2[CH:22]=[C:21]([C:33]3[CH:38]=[CH:37][N:36]=[C:35]4[NH:39][CH:40]=[CH:41][C:34]=34)[CH:20]=[N:19]2)[CH2:7][N:6]([C:8]2[N:9]=[CH:10][C:11]([C:14]([O:16][CH3:17])=[O:15])=[N:12][CH:13]=2)[CH2:5]1)#[N:2]

Participants

7

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 222736434-Bromo-1H-pyrrolo[2,3-b]pyridineHCID 71143602Methyl 5-{3-(cyanomethyl)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]azetidin-1-yl}pyrazine-2-carboxylate

Product 1

HCID 71143560Methyl 5-{3-(cyanomethyl)-3-[4-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-1-yl]azetidin-1-yl}pyrazine-2-carboxylateYield 54.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of methyl 5-{3-(cyanomethyl)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]azetidin-1-yl}pyrazine-2-carboxylate (0.28 g, 0.66 mmol), 4-bromo-1H-pyrrolo[2,3-b]pyridine (0.14 g, 0.72 mmol), tetrakis(triphenylphosphine)palladium(0) (0.04 g, 0.03 mmol) and sodium bicarbonate (0.28 g, 3.3 mmol) in a solution of water (0.5 mL) and 1,4-dioxane (1 mL) was degassed for a while and sealed. The mixture was stirred at 85° C. for 3 h. After cooling the mixture was diluted with ethyl acetate. The organic solution was washed with water and brine, dried over Na2SO4. After filtration the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with methanol in methylene chloride (0-5%) to afford the desired product (0.15 g). LCMS (M+H)+: m/z=415.2.

Workup

  1. customwas degassed for a while
  2. customsealed
  3. temperatureAfter cooling the mixture
  4. additionwas diluted with ethyl acetate
  5. washThe organic solution was washed with water and brine
  6. dry with materialdried over Na2SO4
  7. filtrationAfter filtration the filtrate
  8. concentrationwas concentrated under reduced pressure
  9. customThe residue was purified by flash chromatography on a silica gel column with methanol in methylene chloride (0-5%)

Sources & evidence

ORD record
ord-7031a81d33474e70917fd1c59a2f8cfb
Source dataset
uspto-grants-2015_05
Patent number
US09023840B2

Reaction notes

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