N-(tert-butoxycarbonyl)glycine → Tert-Butyl (2-oxo-2-{(3R)-3-[(6-pyrazolo[1,5-a]pyridin-3-ylpyrazin-2-yl)amino]piperidin-1-yl}ethyl)carbamate

HRID 1500769Notes

Reaction equation

HRID 1500769 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.[NH:46]1[CH2:51][CH2:50][CH2:49][C@@H:48]([NH:52][C:53]2[CH:58]=[N:57][CH:56]=[C:55]([C:59]3[CH:60]=[N:61][N:62]4[CH:67]=[CH:66][CH:65]=[CH:64][C:63]=34)[N:54]=2)[CH2:47]1>CN(C=O)C>[O:12]=[C:10]([N:46]1[CH2:51][CH2:50][CH2:49][C@@H:48]([NH:52][C:53]2[CH:58]=[N:57][CH:56]=[C:55]([C:59]3[CH:60]=[N:61][N:62]4[CH:67]=[CH:66][CH:65]=[CH:64][C:63]=34)[N:54]=2)[CH2:47]1)[CH2:9][NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58303584(R)-N-(Piperidin-3-yl)-6-(pyrazolo[1,5-a]pyridin-3-yl)pyrazin-2-amine

Product 1

HCID 86691788Tert-Butyl (2-oxo-2-{(3R)-3-[(6-pyrazolo[1,5-a]pyridin-3-ylpyrazin-2-yl)amino]piperidin-1-yl}ethyl)carbamateYield 57.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

[(Tert-Butoxycarbonyl)amino]acetic acid (65 mg, 0.37 mmol), 0-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (142 mg, 0.37 mmol) and diisopropylethylamine (65 mL, 0.37 mmol) were added to a solution of (R)—N-(piperidin-3-yl)-6-(pyrazolo[1,5-a]pyridin-3-yl)pyrazin-2-amine (Preparation 28b, 100 mg, 0.34 mmol) in N,N′-dimethylformamide (2 mL) and the resulting mixture was stirred at ambient temperature overnight. The reaction mixture was then partitioned between ethyl acetate and water and the organic layer was separated, washed with brine, dried (MgSO4) and evaporated. The residue was purified by reverse phase chromatography (C-18 silica from Waters, water/1:1 acetonitrile-methanol as eluents [0.1% v/v formic acid buffered] 0% to 100%) to yield the title compound (88 mg, 57%).

Workup

  1. customThe reaction mixture was then partitioned between ethyl acetate and water
  2. customthe organic layer was separated
  3. washwashed with brine
  4. dry with materialdried (MgSO4)
  5. customevaporated
  6. customThe residue was purified by reverse phase chromatography (C-18 silica from Waters, water/1:1 acetonitrile-methanol as eluents [0.1% v/v formic acid

Sources & evidence

ORD record
ord-ce2c17cb06de47c7b06ac2b899c88a09
Source dataset
uspto-grants-2015_12
Patent number
US09206183B2

Reaction notes

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