Sodium Bicarbonate → HCID 118214757, compound

HRID 2205615Notes

Reaction equation

HRID 2205615 reaction equation
Br[C:2]1[CH:3]=[C:4]2[N:13]([CH3:14])[CH:12]=[CH:11][C:5]2=[N:6][C:7]=1[C@@H:8]([NH2:10])[CH3:9].[C@H:15]12[CH2:21][C@H:18]([NH:19][CH2:20]1)[CH2:17][N:16]2[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23].CC([O-])(C)C.[K+].C([O-])(O)=O.[Na+]>CCOC(C)=O.O1CCOCC1>[NH2:10][C@H:8]([C:7]1[N:6]=[C:5]2[CH:11]=[CH:12][N:13]([CH3:14])[C:4]2=[CH:3][C:2]=1[N:19]1[CH2:20][C@@H:15]2[CH2:21][C@H:18]1[CH2:17][N:16]2[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH3:9]

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 11521263(1S,4S)-2-Boc-2,5-diazabicyclo[2.2.1]heptaneHCID 23665647Potassium tert-butoxideHCID 86707977(S)-1-(6-Bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine

Product 1

HCID 118214757HCID 118214757, compoundYield 33.2%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a 50 mL pear flask were added (S)-1-(6-bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine (628 mg, 2.471 mmol) and (1S,4S)-tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (906 mg, 4.57 mmol). After evacuating the flask and flushing it with nitrogen, 1,4-dioxane (5.9 mL) and potassium 2-methylpropan-2-olate (1 M in THF, 5.4 mL, 5.4 mmol) were added. The mixture was heated to 90° C. for 1 hour. The reaction mixture was then cooled and worked up with saturated NaHCO3 and EtOAc. The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by preparative HPLC (acid mode, 25-65% ACN/water gradient). The product-containing fractions were combined, neutralized with a small amount of saturated NaHCO3, concentrated in vacuo to remove ACN, and then extracted with EtOAc. The organic layers were combined, dried over MgSO4, filtered, and concentrated in vacuo to give the title compound (305 mg, 33.2%). ESI-MS m/z [M+H]+ calc'd for C20H29N5O2, 372. found 372.

Workup

  1. customAfter evacuating the flask
  2. additionwere added
  3. temperatureThe reaction mixture was then cooled
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by preparative HPLC (acid mode, 25-65% ACN/water gradient)
  8. concentrationconcentrated in vacuo
  9. customto remove ACN
  10. extractionextracted with EtOAc
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6a796055cf8744219b9f2ed217811db4
Source dataset
uspto-grants-2016_06
Patent number
US09371321B2

Reaction notes

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