tert-Butyl piperazine-1-carboxylate → HCID 118207781, compound

HRID 2205593Notes

Reaction equation

HRID 2205593 reaction equation
[N:1]1([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.Br[C:15]1[CH:16]=[C:17]2[N:26]([CH3:27])[CH:25]=[CH:24][C:18]2=[N:19][C:20]=1[C@@H:21]([NH2:23])[CH3:22].CC([O-])(C)C.[K+].C([O-])(O)=O.[Na+]>O1CCOCC1>[NH2:23][C@H:21]([C:20]1[N:19]=[C:18]2[CH:24]=[CH:25][N:26]([CH3:27])[C:17]2=[CH:16][C:15]=1[N:4]1[CH2:5][CH2:6][N:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:2][CH2:3]1)[CH3:22]

Participants

6

Reactant 4

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 516892Sodium BicarbonateHCID 23665647Potassium tert-butoxideHCID 86707977(S)-1-(6-Bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine

Product 1

HCID 118207781HCID 118207781, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a 50 mL pear flask were added tert-butyl piperazine-1-carboxylate (2.44 g, 12.7 mmol) and (S)-1-(6-bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine (1.54 g, 6.06 mmol) in 1,4-dioxane (15 mL). To this solution was added potassium 2-methylpropan-2-olate (1 M in THF) (13.3 mL, 13.3 mmol), and the resulting mixture was heated to 90° C. for 45 minutes. After cooling for 10 minutes, the red mixture was poured into saturated NaHCO3 (300 mL) and then extracted with EtOAc (3×). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo to give crude product, which was purified by preparative HPLC (acid mode, 25-65% ACN/water gradient). The product-containing fractions were combined, concentrated in vacuo, and then partitioned between saturated NaHCO3 and EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated to give the title compound (872 mg, 40.0%). ESI-MS m/z [M+H]+ calc'd for C19H29N5O2, 360. found 360.

Workup

  1. temperatureAfter cooling for 10 minutes
  2. extractionextracted with EtOAc (3×)
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give crude product, which
  7. customwas purified by preparative HPLC (acid mode, 25-65% 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-e7b18ddbcdf643ccb8dfbd4800a2a005
Source dataset
uspto-grants-2016_06
Patent number
US09371321B2

Reaction notes

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