Acetic Acid → HCID 67267101, compound

HRID 602515Notes

Reaction equation

HRID 602515 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])=[C:4]([CH3:15])[CH:3]=1.[Cl:16][C:17]1[CH:32]=[CH:31][C:20]([O:21][C:22]2[N:26]([CH3:27])[N:25]=[C:24]([CH3:28])[C:23]=2[CH:29]=O)=[CH:19][CH:18]=1.C([BH3-])#N.[Na+].C(O)(=O)C>C(#N)C.CO>[Cl:16][C:17]1[CH:32]=[CH:31][C:20]([O:21][C:22]2[N:26]([CH3:27])[N:25]=[C:24]([CH3:28])[C:23]=2[CH2:29][NH:1][C:2]2[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:11])([CH3:12])[CH3:13])=[C:4]([CH3:15])[CH:3]=2)=[CH:19][CH:18]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 960627N-(4-amino-2-methylphenyl)-2,2-dimethylpropanamideHCID 27668545-(4-chlorophenoxy)-1,3-dimethyl-1H-pyrazole-4-carbaldehydeHCID 5003444Sodium cyanoborohydride

Product 1

HCID 67267101HCID 67267101, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
170 °C

Procedure

A mixture of N-(4-Amino-2-methylphenyl)-2,2-dimethylpropionamide (300 mg, 1.45 mmol) and 5-(4-Chlorophenoxy)-1,3-dimethyl-1H-pyrazole-4-carbaldehyde (360 mg, 1.45 mmol) in acetonitrile (4 mL) was heated and stirred at 170° C. under microwave irradiation for 20 minutes. The obtained reaction mixture was added carefully into solution of sodium cyanoborohydride (0.36 g) in methanol followed by acetic acid (1 mL). After 60 minutes it was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution and the organic layer was evaporated. The title compound was separated by flash chromatography on SiO2 with gradient heptane-ethyl acetate and then precipitated from ethyl acetate with heptane. Yield 112 mg, 18%. LC/MS-TOF (m/z) 441; RT=2.34, (UV, ELSD) 98%, 100%. 1H NMR (DMSO-d6): 1.18 (s, 9H), 1.96 (s, 3H), 2.15 (s, 3H), 3.47 (s, 3H), 3.75 (d, 2H), 5.4 (t, 1H, NH), 6.29 (dd, 1H), 6.33 (d, 1H), 6.24 (d, 1H), 6.99 (d, 2H), 7.41 (d, 2H), 8.58 (s, 1H, NH).

Workup

  1. temperaturewas heated
  2. customThe obtained reaction mixture
  3. customAfter 60 minutes it was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution
  4. customthe organic layer was evaporated
  5. customThe title compound was separated by flash chromatography on SiO2 with gradient heptane-ethyl acetate
  6. customprecipitated from ethyl acetate with heptane
  7. customRT=2.34, (UV, ELSD) 98%, 100%

Sources & evidence

ORD record
ord-e359d47ed13a41478d1a280c3bcd96c7
Source dataset
uspto-grants-2011_03
Patent number
US07906537B2

Reaction notes

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