Sodium Bicarbonate → HCID 118214744, compound

HRID 2205602Notes

Reaction equation

HRID 2205602 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+]>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

6

Reactant 4

HCID 516892Sodium BicarbonateHCID 10081508tert-Butyl (2S)-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 118214744HCID 118214744, compoundYield 38.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a 250 mL round-bottom flask were added (S)-tert-butyl 2-methylpiperazine-1-carboxylate (3.94 g, 19.7 mmol) and (S)-1-(6-bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine (2.5 g, 9.8 mmol) in 1,4-dioxane (23 mL). To the resulting solution was added potassium 2-methylpropan-2-olate (1 M in THF, 21 mL, 21 mmol), and the mixture was heated to 90° C. for 1 hour. After cooling for 10 minutes, the red mixture was poured into 300 mL of saturated NaHCO3 and then 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 (acid mode, 25-50% ACN/water gradient). The product-containing fractions were combined, concentrated in vacuo, and partitioned between saturated NaHCO3 and EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated to give the title compound (1.41 g, 38.4%). ESI-MS m/z [M+H]+ calc'd for C20H31N5O2, 374. found 374.

Workup

  1. temperatureAfter cooling for 10 minutes
  2. extractionextracted 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 (acid mode, 25-50% ACN/water gradient)
  8. concentrationconcentrated in vacuo
  9. custompartitioned between saturated NaHCO3 and EtOAc
  10. dry with materialThe combined organic layers were dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-64ce1cf522f14bd3bf0a055cbf422e0a
Source dataset
uspto-grants-2016_06
Patent number
US09371321B2

Reaction notes

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