Sodium Carbonate → HCID 178487044, compound

HRID 1854513Notes

Reaction equation

HRID 1854513 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][O:26][C:27]1[CH:28]=[C:29]2[C:33](=[CH:34][CH:35]=1)[N:32]([CH3:36])[CH:31]=[C:30]2B1OC(C)(C)C(C)(C)O1.C([O-])([O-])=O.[Na+].[Na+].[OH-].[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.CO>[CH3:25][O:26][C:27]1[CH:28]=[C:29]2[C:33](=[CH:34][CH:35]=1)[N:32]([CH3:36])[CH:31]=[C:30]2[C:2]1[NH:14][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

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 14798Sodium HydroxideHCID 580098415-methoxy-1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indoleHCID 580099867-Iodo-1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine

Product 1

HCID 178487044HCID 178487044, compoundYield 22%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
87.5 °C

Procedure

A flask was charged with 7-iodo-1-methyl-6-tosyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine (0.200 g, 0.442 mmol, Example #41, Step C), 5-methoxy-1-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (0.140 g, 0.486 mmol, Preparation #31), Pd(PPh3)4 (0.036 g, 0.031 mmol, Strem) and Na2CO3 (0.117 g, 1.11 mmol) in 1,4-dioxane:water (3:1, 10 mL). The reaction mixture was heated at about 85-90° C. for about 5 h. The reaction mixture was filtered, concentrated to dryness under reduced pressure to give a crude solid that was added to a microwave reaction vessel. MeOH (3 mL) and aqueous NaOH (5 N, 0.412 mL, 2.06 mmol) were added and the 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 in vacuo, and purified by silica gel chromatography eluting with a gradient of 5-68% EtOAc in heptane to give 7-(5-methoxy-1-methyl-1H-indol-3-yl)-1-methyl-1,6-dihydropyrazolo[3,4-d]pyrrolo[2,3-b]pyridine (0.015 g, 22% over 2 steps): LC/MS (Table 2, Method d) Rt=1.30 min; MS m/z: 332 (M+H)+.

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationconcentrated to dryness under reduced pressure
  3. customto give a crude solid that
  4. additionwas added to a microwave reaction vessel
  5. customthe 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 in vacuo
  10. custompurified by silica gel chromatography
  11. washeluting with a gradient of 5-68% EtOAc in heptane

Sources & evidence

ORD record
ord-519717165ef542d1a69bff66994e2884
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

Loading…