Dimethylformamide → tert-Butyl 5-((1H-pyrazole-4-carboxamido)methyl)-4,6-dimethylpyridin-2-ylcarbamate

HRID 928437Notes

Reaction equation

HRID 928437 reaction equation
CN(C(ON1[N:17]=[N:16][C:11]2[CH:12]=[CH:13]C=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[NH2:34][CH2:35][C:36]1[C:37]([CH3:51])=[CH:38][C:39]([NH:43][C:44](=[O:50])[O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[N:40][C:41]=1[CH3:42].CN([CH:55]=[O:56])C>C(OCC)(=O)C.O>[NH:17]1[CH:13]=[C:12]([C:55]([NH:34][CH2:35][C:36]2[C:37]([CH3:51])=[CH:38][C:39]([NH:43][C:44](=[O:50])[O:45][C:46]([CH3:47])([CH3:48])[CH3:49])=[N:40][C:41]=2[CH3:42])=[O:56])[CH:11]=[N:16]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 22475372N-[5-(aminomethyl)-4,6-dimethyl(2-pyridyl)] (tert-butoxy)carboxamide

Product 1

HCID 58081315tert-Butyl 5-((1H-pyrazole-4-carboxamido)methyl)-4,6-dimethylpyridin-2-ylcarbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
23 °C

Procedure

To a solution of ethyl pyrazole-4-carboxylate (1 g, 7.14 mmol) in EtOH/THF/water 2/1/1 (8 ml) was added LiOH monohydrate (329 mg, 7.84 mmol). Reaction mixture was stirred for 1 day at 80° C. 4M HCl in dioxane (1.962 ml, 7.85 mmol) was added to reaction mixture which was evaporated to dryness to afford the free carboxylic acid. This material (1.218 g, 7.14 mmol) was dissolved in DMF (30 ml), to which were added HBTU (4.06 g, 10.71 mmol), DIPEA (3.74 ml, 21.43 mmol) then tert-butyl (5-(aminomethyl)-4,6-dimethylpyridin-2-yl)carbamate (2.69 g, 10.71 mmol). Reaction mixture was stirred overnight at 23° C. Reaction mixture was diluted with ethyl acetate and water. Phases were separated and organic layer was washed with NaHCO3 sat. solution and brine. Organic layer was dried over sodium sulfate, filtered and evaporated to afford the crude material, which was purified by normal phase chromatography (silica gel, 100% ethyl acetate) followed by reverse phase chromatography (C18, acetonitrile/water) to afford the title compound. HPLC (Method G) Rt=1.245 min, MS (Method V) [M+H]+=346.2.

Workup

  1. customReaction mixture
  2. customReaction mixture
  3. customPhases were separated
  4. washorganic layer was washed with NaHCO3 sat. solution and brine
  5. dry with materialOrganic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customto afford the crude material, which
  9. customwas purified by normal phase chromatography (silica gel, 100% ethyl acetate)

Sources & evidence

ORD record
ord-42ea571aa27e4dca957f97f85ea01aea
Source dataset
uspto-grants-2016_03
Patent number
US09290485B2

Reaction notes

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