Sodium Carbonate → HCID 178480013, compound

HRID 2204666Notes

Reaction equation

HRID 2204666 reaction equation
I[C:2]1[N:14](S(C2C=CC(C)=CC=2)(=O)=O)[C:5]2=[N:6][CH:7]=[C:8]3[CH:12]=[N:11][N:10]([CH3:13])[C:9]3=[C:4]2[CH:3]=1.[CH3:25][N:26]1[CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH:28]=[N:27]1.C([O-])([O-])=O.[Na+].[Na+].[OH-].[Na+]>O1CCOCC1.O.CO>[CH3:13][N:10]1[C:9]2=[C:4]3[CH:3]=[C:2]([C:29]4[CH:28]=[N:27][N:26]([CH3:25])[CH:30]=4)[NH:14][C:5]3=[N:6][CH:7]=[C:8]2[CH:12]=[N:11]1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 580099867-Iodo-1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine

Product 1

HCID 178480013HCID 178480013, compoundYield 50.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

A flask was charged with 7-iodo-1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine (0.134 g, 0.296 mmol, Example #41, Step C), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.074 g, 0.36 mmol), (PPh3)4 (0.024 g, 0.021 mmol, Strem) and Na2CO3 (0.079 g, 0.74 mmol) in 1,4-dioxane:water (3:1, 10 mL) The reaction was heated at about 80° C. for about 12 h. The mixture was filtered and the filtrate was concentrated under reduced pressure to give a solid that was added to a 5 mL microwave reaction vial. MeOH (3 mL) and aqueous NaOH (5 N, 0.77 ml, 3.8 mmol) were added and the reaction vessel was sealed and heated to about 120° C. in a microwave for about 20 min (250 psi maximum pressure, 2 min ramp time, 300 max watts). The reaction mixture was filtered and washed with MeOH. The filtrate was concentrated, redissolved in MeOH/DCM, and purified by silica gel chromatography (12 g column) eluting with a gradient of 0-5% MeOH in DCM. The product-containing fractions were combined and concentrated to give 1-methyl-7-(1-methyl-1H-pyrazol-4-yl)-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine (0.038 g, 39% over 2 steps): LC/MS (Table 2, Method d) Rt=1.13 min; MS m/z: 253 (M+H)+.

Workup

  1. filtrationThe mixture was filtered
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customto give a solid
  4. additionthat was added to a 5 mL microwave reaction vial
  5. customthe reaction vessel was sealed
  6. temperatureheated to about 120° C. in a microwave for about 20 min (250 psi maximum pressure, 2 min ramp time, 300 max watts)
  7. filtrationThe reaction mixture was filtered
  8. washwashed with MeOH
  9. concentrationThe filtrate was concentrated
  10. dissolutionredissolved in MeOH/DCM
  11. custompurified by silica gel chromatography (12 g column)
  12. washeluting with a gradient of 0-5% MeOH in DCM
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-79ac8c68e1ea4b578fb5d71670cda8ff
Source dataset
uspto-grants-2016_06
Patent number
US09365579B2

Reaction notes

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