Potassium Carbonate → HCID 118214747, compound

HRID 2205607Notes

Reaction equation

HRID 2205607 reaction equation
[CH3:1][C@@H:2]1[CH2:7][NH:6][CH2:5][CH2:4][N:3]1[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].Br[C:16]1[CH:17]=[C:18]2[N:27]([CH3:28])[CH:26]=[CH:25][C:19]2=[N:20][C:21]=1[C@@H:22]([NH2:24])[CH3:23].CC([O-])(C)C.[K+].C([O-])(O)=O.[Na+].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1>[NH2:24][C@H:22]([C:21]1[N:20]=[C:19]2[CH:25]=[CH:26][N:27]([CH3:28])[C:18]2=[CH:17][C:16]=1[N:6]1[CH2:5][CH2:4][N:3]([C:8]([O:10][C:11]([CH3:13])([CH3:12])[CH3:14])=[O:9])[C@H:2]([CH3:1])[CH2:7]1)[CH3:23]

Participants

7

Reactant 5

HCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 10262201tert-Butyl (2R)-2-methylpiperazine-1-carboxylateHCID 23665647Potassium tert-butoxideHCID 86707977(S)-1-(6-Bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine

Product 1

HCID 118214747HCID 118214747, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a 50 mL pear flask were added (R)-tert-butyl 2-methylpiperazine-1-carboxylate (156 mg, 0.777 mmol) and (S)-1-(6-bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine (94 mg, 0.370 mmol) in 1,4-dioxane (0.92 mL). Potassium 2-methylpropan-2-olate (1 M in THF, 0.81 mL, 0.81 mmol) was added, and the mixture was heated to 90° C. for 45 minutes. After cooling for 10 minutes, the red mixture was poured into saturated NaHCO3 and the pH was adjusted to ˜10 by adding K2CO3. The mixture was extracted with EtOAc (3×). The organic layers were combined, dried over MgSO4, filtered, and concentrated in vacuo to give crude product, which was purified by preparative HPLC (basic mode, 30-55% ACN/water gradient). The product-containing fractions were combined, concentrated in vacuo, and then partitioned between saturated NaHCO3 and EtOAc. The organic phase was dried over MgSO4, filtered, and concentrated to give the title compound as a colorless oil (45 mg, 33%). ESI-MS m/z [M+H]+ calc'd for C20H31N5O2, 374. found 374.

Workup

  1. temperatureAfter cooling for 10 minutes
  2. extractionThe mixture was extracted with EtOAc (3×)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give crude product, which
  7. customwas purified by preparative HPLC (basic mode, 30-55% ACN/water gradient)
  8. concentrationconcentrated in vacuo
  9. custompartitioned between saturated NaHCO3 and EtOAc
  10. dry with materialThe organic phase was dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-d9377c8bbea84b7d8b46ef4552d14e2f
Source dataset
uspto-grants-2016_06
Patent number
US09371321B2

Reaction notes

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