Water → [3-methyl-4-((1S,4S)-2-methyl-2,5-diazabicyclo[2.2.1]heptan-5-yl)phenyl][N,N-bis(tert-butoxycarbonyl)]guanidine

HRID 1875695Notes

Reaction equation

HRID 1875695 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[N:9]1[CH2:14][C@@H:13]2[CH2:15][C@H:10]1[CH2:11][N:12]2[CH3:16])[NH2:5].C(OC(N[C:25](=[N:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[N:26]1C=CC=N1)=O)(C)(C)C.[OH2:39]>CN(C=O)C>[CH3:1][C:2]1[CH:3]=[C:4]([N:5]=[C:25]([NH2:26])[N:31]([C:32]([O:34][C:35]([CH3:36])([CH3:37])[CH3:38])=[O:33])[C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:39])[CH:6]=[CH:7][C:8]=1[N:9]1[CH2:14][C@@H:13]2[CH2:15][C@H:10]1[CH2:11][N:12]2[CH3:16]

Participants

5

Reactant 3

HCID 962WaterHCID 4428040N,N'-Bis(tert-butoxycarbonyl)-1H-pyrazole-1-carboxamidineHCID 686333063-Methyl-4-[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl]aniline

Product 1

HCID 68983667[3-methyl-4-((1S,4S)-2-methyl-2,5-diazabicyclo[2.2.1]heptan-5-yl)phenyl][N,N-bis(tert-butoxycarbonyl)]guanidineYield 97%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

On a larger scale, 3-methyl-4-[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl]aniline (10.0 g, 45.8 mmol) and 1-(tert-butoxycarbonylamino(tert-butoxycarbonylimino)methyl)pyrazole (15.0 g, 48.2 mmol) were combined in DMF (25 mL) and stirred at ambient temperature. The progress of homogenous reaction was monitored by LC/MS. After 36 h, the reaction mixture was added slowly to water (300 mL) in a beaker with vigorous stirring, whereupon a precipitate formed. The reaction flask was rinsed with DMF (2×5 mL) and transferred to the beaker. Suction filtration of the suspension, further washing of the resulting filter cake with water (200 mL) and air drying under suction provided 20.5 g (97%) of [3-methyl-4-((1S,4S)-2-methyl-2,5-diazabicyclo[2.2.1]heptan-5-yl)phenyl][N,N-bis(tert-butoxycarbonyl)]guanidine (Ja) as a off-white purple solid; LCMS: purity: 96%; MS (m/e): 449 (MH+).

Workup

  1. customThe progress of homogenous reaction
  2. customformed
  3. washThe reaction flask was rinsed with DMF (2×5 mL)
  4. filtrationSuction filtration of the suspension
  5. washfurther washing of the resulting
  6. filtrationfilter cake with water (200 mL) and air
  7. customdrying under suction

Sources & evidence

ORD record
ord-660c8c75bd4049c58eed59662fb14deb
Source dataset
uspto-grants-2012_11
Patent number
US08309566B2

Reaction notes

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