Sodium Carbonate → 1-Methyl-7-(3-(methylsulfonyl)phenyl)-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine

HRID 2204664Notes

Reaction equation

HRID 2204664 reaction equation
I[C:2]1[N:14]([S:15]([C:18]2[CH:24]=[CH:23][C:21]([CH3:22])=[CH:20][CH:19]=2)(=[O:17])=[O:16])[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][S:26]([C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][CH:34]=1)(=[O:28])=[O:27].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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>[CH3:13][N:10]1[C:9]2=[C:4]3[CH:3]=[C:2]([C:33]4[CH:32]=[CH:31][CH:30]=[C:29]([S:26]([CH3:25])(=[O:28])=[O:27])[CH:34]=4)[N:14]([S:15]([C:18]4[CH:24]=[CH:23][C:21]([CH3:22])=[CH:20][CH:19]=4)(=[O:17])=[O:16])[C:5]3=[N:6][CH:7]=[C:8]2[CH:12]=[N:11]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27735423-(Methylsulfonyl)phenylboronic acidHCID 580099867-Iodo-1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine

Product 1

HCID 690150661-Methyl-7-(3-(methylsulfonyl)phenyl)-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridineYield 126.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
90 °C

Procedure

A mixture of 7-iodo-1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine (0.134 g, 0.296 mmol), 3-(methylsulfonyl)phenylboronic acid (0.711 g, 0.356 mmol, Combi-Blocks), Pd(PPh3)4 (0.24 g, 0.021 mmol, Strem), Na2CO3 (0.790 g, 0.741 mmol) in 1,4-dioxane:water (3:1, 10 mL) was heated to about 90° C. for about 5 h. The reaction mixture was filtered through a plug of Celite®. The filtrate was washed with water (10 mL), dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to give 1-methyl-7-(3-(methylsulfonyl)phenyl)-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine (0.180 g, 0.375 mmol) that was dissolved in MeOH (3 mL) and treated with aqueous NaOH (5 N, 0.75 mL, 3.8 mmol) The reaction vessel was sealed and heated in a CEM microwave at about 120° C. for about 20 min (250 psi maximum pressure, 2 min ramp time, 300 max watts). The reaction mixture was filtered and washed with MeOH (3 mL). The filtrate was concentrated in vacuo, and purified by silica gel chromatography eluting with a gradient of 0-10% MeOH in DCM to give 1-methyl-7-(3-(methylsulfonyl)phenyl)-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine (0.65 g, 53%): LC/MS (Table 2, Method d) Rt=1.23 min; MS m/z: 327 (M+H)+.

Workup

  1. filtrationThe reaction mixture was filtered through a plug of Celite®
  2. washThe filtrate was washed with water (10 mL)
  3. dry with materialdried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-03affe49b4ed43059b363d8992a58e70
Source dataset
uspto-grants-2016_06
Patent number
US09365579B2

Reaction notes

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