Pivaloyl chloride → HCID 57723209, compound

HRID 1987221Notes

Reaction equation

HRID 1987221 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([NH:17][C:18](=[O:20])[CH3:19])[CH:5]=[CH:6][C:7]=1[NH:8][CH2:9][CH:10]1[CH2:15][CH2:14][CH:13]([F:16])[CH2:12][CH2:11]1.[CH3:21][C:22]([CH3:27])([CH3:26])[C:23](Cl)=O>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:22]([C:27]1[N:8]([CH2:9][CH:10]2[CH2:11][CH2:12][CH:13]([F:16])[CH2:14][CH2:15]2)[C:7]2[CH:6]=[CH:5][C:4]([NH:17][C:18](=[O:20])[CH3:19])=[CH:3][C:2]=2[N:1]=1)([CH3:26])([CH3:23])[CH3:21]

Participants

5

Reactant 2

HCID 62493Pivaloyl chlorideHCID 57723216HCID 57723216, compound

Product 1

HCID 57723209HCID 57723209, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

N-(3-Amino-4-{[(4-fluorocyclohexyl)methyl]amino}phenyl)acetamide (300 mg, 1.07 mmol) and DMAP (25 mg, 0.214 mmol) were dissolved in 10 mL of DCM. Trimethylacetyl chloride (0.145 mL, 1.18 mmol) was added dropwise and the solution was stirred at rt for 1 h. The solution was washed with aqueous NaHCO3 solution, brine and dried over anhydrous MgSO4. The residue was dissolved in 5 mL of AcOH and was heated at 150° C. for 2.5 h using a Personal Chemistry microwave apparatus. The solvent was evaporated. The residue was dissolved in EtOAc and washed with aqueous NaHCO3 solution, brine and dried over anhydrous MgSO4. The crude product was purified by silica gel flash chromatography using 2:1/acetone:hexanes as eluent. Yield: 196 mg (53%). 1HNMR (400 MHz, CHLOROFORM-D) δ 1.14-1.25 (m, 2 H), 1.37-1.45 (m, 1 H), 1.43-1.51 (m, 1 H), 1.54-1.57 (m, 9 H), 1.70-1.78 (m, 2 H), 1.70-1.77 (m, 1 H), 2.02-2.08 (m, 1 H), 2.10-2.17 (m, 1 H), 2.19-2.21 (m, 3 H), 4.12-4.19 (m, 2 H), 4.53 (m, 0.3 H), 4.73 (m, 0.3 H), 4.78 (m, 0.2 H), 4.90 (m, 0.2 H), 7.21-7.29 (m, 1 H), 7.30 (s, 1 H), 7.50-7.57 (m, 1 H), 7.64-7.67 (m, 1 H).

Workup

  1. washThe solution was washed with aqueous NaHCO3 solution, brine
  2. dry with materialdried over anhydrous MgSO4
  3. dissolutionThe residue was dissolved in 5 mL of AcOH
  4. temperaturewas heated at 150° C. for 2.5 h
  5. customThe solvent was evaporated
  6. dissolutionThe residue was dissolved in EtOAc
  7. washwashed with aqueous NaHCO3 solution, brine
  8. dry with materialdried over anhydrous MgSO4
  9. customThe crude product was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-2c8d5ac9cc0c4476b017b7b348f2149b
Source dataset
uspto-grants-2009_06
Patent number
US07550495B2

Reaction notes

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