Acetic Acid → tert-Butyl (2-{[4-(1-{1,3-dimethyl-1H-pyrazol-4-ylmethyl}piperidin-4-yl)benzoyl]amino}phenyl)carbamate

HRID 1028239Notes

Reaction equation

HRID 1028239 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:29]=[CH:28][C:10]([C:11]([NH:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:12])=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.[CH3:30][N:31]1[CH:35]=[C:34]([CH:36]=O)[C:33]([CH3:38])=[N:32]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClCCl.C(OCC)C>[CH3:30][N:31]1[CH:35]=[C:34]([CH2:36][N:1]2[CH2:6][CH2:5][CH:4]([C:7]3[CH:29]=[CH:28][C:10]([C:11]([NH:13][C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=4[NH:20][C:21](=[O:27])[O:22][C:23]([CH3:25])([CH3:26])[CH3:24])=[O:12])=[CH:9][CH:8]=3)[CH2:3][CH2:2]2)[C:33]([CH3:38])=[N:32]1

Participants

8

Reactant 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 8472851,3-dimethyl-1H-pyrazole-4-carbaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 59830875Tert-butyl 2-[(4-piperidin-4-ylbenzoyl)amino]phenylcarbamate

Product 1

HCID 59830877tert-Butyl (2-{[4-(1-{1,3-dimethyl-1H-pyrazol-4-ylmethyl}piperidin-4-yl)benzoyl]amino}phenyl)carbamateYield 87.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×

Procedure

tert-Butyl 2-[(4-piperidin-4-ylbenzoyl)amino]phenylcarbamate (6.83 g, 17.3 mmol) and 1,3-dimethyl-1H-pyrazole-4-carbaldehyde (3.0 g, 24.2 mmol) were dissolved in dichloromethane (150 ml). Acetic acid (996 μl, 17.3 mmol) was then added and the reaction mixture allowed to stir at room temperature for four hours. Sodium triacetoxyborohydride (5.49 g, 25.9 mmol) was then added and reaction mixture stirred for a further 18 hours. Saturated aqueous sodium bicarbonate solution (300 ml) was then carefully added followed by dichloromethane (100 ml). The organic layer was separated and the aqueous layer re-extracted with more dichloromethane (150 ml). The combined organic extracts were dried over magnesium sulphate, filtered and evaporated to dryness. The residue obtained was purified by flash chromatography on silica, eluting with a 5% (v/v) solution of methanol in dichloromethane followed by a rising gradient of 5-10% (v/v) methanol in dichloromethane to afford a clear gum, which was taken up in diethyl ether and evaporated to dryness to afford the title compound (7.61 g, 87%); NMR Spectrum: (DMSO d6) δ 1.43 (s, 9H), 1.69 (m, 4H), 1.98 (m, 2H), 2.10 (s, 3H), 2.56 (m, 1H), 2.92 (m, 2H), 3.26 (s, 2H), 3.70 (s, 3H), 7.15 (m, 2H), 7.40 (m, 3H), 7.52 (m, 2H), 7.87 (d, 2H), 8.60 (s, 1H), 9.73 (s, 1H); Mass Spectrum: M+H+ 504.

Workup

  1. customreaction mixture
  2. stirringstirred for a further 18 hours
  3. customThe organic layer was separated
  4. extractionthe aqueous layer re-extracted with more dichloromethane (150 ml)
  5. dry with materialThe combined organic extracts were dried over magnesium sulphate
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe residue obtained
  9. customwas purified by flash chromatography on silica
  10. washeluting with a 5% (v/v) solution of methanol in dichloromethane
  11. customto afford a clear gum, which
  12. customevaporated to dryness

Sources & evidence

ORD record
ord-97bda5a1fa2946e49f78cefb9d9a5fe3
Source dataset
uspto-grants-2014_05
Patent number
US08735429B2

Reaction notes

Loading…