tert-Butyl 3-(methylamino)azetidine-1-carboxylate → tert-Butyl (S)-3-((5-(1-aminoethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)(methyl)amino)azetidine-1-carboxylate

HRID 2205625Notes

Reaction equation

HRID 2205625 reaction equation
[CH3:1][NH:2][CH:3]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:4]1.CC(C)([O-])C.[K+].Br[C:21]1[CH:22]=[C:23]2[N:32]([CH3:33])[CH:31]=[CH:30][C:24]2=[N:25][C:26]=1[C@@H:27]([NH2:29])[CH3:28]>>[NH2:29][C@H:27]([C:26]1[N:25]=[C:24]2[CH:30]=[CH:31][N:32]([CH3:33])[C:23]2=[CH:22][C:21]=1[N:2]([CH3:1])[CH:3]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:12])([CH3:11])[CH3:13])=[O:8])[CH2:4]1)[CH3:28]

Participants

4

Reactant 3

HCID 23153172tert-Butyl 3-(methylamino)azetidine-1-carboxylateHCID 23665647Potassium tert-butoxideHCID 86707977(S)-1-(6-Bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine

Product 1

HCID 118214763tert-Butyl (S)-3-((5-(1-aminoethyl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-6-yl)(methyl)amino)azetidine-1-carboxylate

Procedure

Into a 8 mL 2-necked round-bottom flask equipped for stirring and fitted with a septum cap were added tert-butyl 3-(methylamino)azetidine-1-carboxylate (0.220 g, 1.181 mmol), potassium tert-butoxide (0.132 g, 1.181 mmol) and 2-Me THF (2 mL). The reaction mixture was heated to 85° C. (S)-1-(6-Bromo-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethan-1-amine (0.100 g, 0.394 mmol) in 2-Me THF (2.000 mL) was added dropwise via syringe and the reaction mixture was stirred at 85° C. for 37 minutes. The reaction mixture was then cooled and partitioned between water and ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered, concentrated, and dried under vacuum. The crude product was purified by preparative HPLC (acid mode, 20-45% ACN/water gradient) to give the title compound as a light brown film (27.4 mg, 15%). ESI-MS m/z [M+H]+ calc'd for C19H29N5O2, 360. found 360.

Workup

  1. customInto a 8 mL 2-necked round-bottom flask equipped
  2. customfitted with a septum
  3. customcap
  4. additionwas added dropwise via syringe
  5. stirringthe reaction mixture was stirred at 85° C. for 37 minutes
  6. temperatureThe reaction mixture was then cooled
  7. custompartitioned between water and ethyl acetate
  8. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customdried under vacuum
  12. customThe crude product was purified by preparative HPLC (acid mode, 20-45% ACN/water gradient)

Sources & evidence

ORD record
ord-d034df6403e04bfaa153acb5d0f7b761
Source dataset
uspto-grants-2016_06
Patent number
US09371321B2

Reaction notes

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