Sodium Carbonate → HCID 68764146, compound

HRID 79575Notes

Reaction equation

HRID 79575 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3](B(O)O)[CH:2]=1.C(=O)([O-])[O-].[Na+].[Na+].Br[C:17]1[C:18]([N:26]2[CH2:31][CH2:30][N:29]([C:32](=[O:53])[C@@H:33]([C:46]3[CH:51]=[CH:50][C:49]([Cl:52])=[CH:48][CH:47]=3)[CH2:34][N:35]([CH:43]([CH3:45])[CH3:44])[C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH2:28][CH2:27]2)=[C:19]2[CH:25]=[CH:24][NH:23][C:20]2=[N:21][CH:22]=1>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>[Cl:52][C:49]1[CH:48]=[CH:47][C:46]([C@H:33]([C:32](=[O:53])[N:29]2[CH2:30][CH2:31][N:26]([C:18]3[C:17]([C:3]4[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=4)=[CH:22][N:21]=[C:20]4[NH:23][CH:24]=[CH:25][C:19]=34)[CH2:27][CH2:28]2)[CH2:34][N:35]([CH:43]([CH3:45])[CH3:44])[C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[CH:51][CH:50]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 68764847(5)-Tert-butyl 3-(4-(5-bromo-1h-pyrrolo [2,3-b]pyridin-4-yl)piperazin-1-yl)-2-(4-chlorophenyl)-3-oxopropyl(isopropyl)carbamate

Product 1

HCID 68764146HCID 68764146, compoundYield 64%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
160 °C

Procedure

Pyridin-3-ylboronic acid (20 mg, 0.17 mmol), PS-tetrakis (41 mg, 0.0041 mmol) and sodium carbonate (18 mg, 0.17 mmol, 2N aqueous solution) were added to (S)-tert-butyl 3-(4-(5-bromo-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)-2-(4-chlorophenyl)-3-oxopropyl(isopropyl)carbamate (50 mg, 0.083 mmol, see Example 4) in degassed (Ar) dioxane (1 mL). The reaction was heated to 160° C. for 1 hour under microwave irradiation. After cooling down, the reaction was diluted with DCM, filtered, dried over MgSO4 and concentrated to dryness. The resulting residue was purified by reverse phase column chromatography (water:ACN 4:1 to 1:9) to yield (S)-tert-butyl 2-(4-chlorophenyl)-3-oxo-3-(4-(5-(pyridin-3-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl)piperazin-1-yl)propyl(isopropyl)carbamate (32 mg, 64% yield) as a solid.

Workup

  1. customin degassed (Ar) dioxane (1 mL)
  2. temperatureAfter cooling down
  3. additionthe reaction was diluted with DCM
  4. filtrationfiltered
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated to dryness
  7. customThe resulting residue was purified by reverse phase column chromatography (water:ACN 4:1 to 1:9)

Sources & evidence

ORD record
ord-e9da5ba0d03445798bb63fa8c713f948
Source dataset
uspto-grants-2014_09
Patent number
US08841304B2

Reaction notes

Loading…