Acetamide → HCID 25196902, compound

HRID 561080Notes

Reaction equation

HRID 561080 reaction equation
[CH:1]1([N:5]2[CH2:10][CH2:9][N:8]([C:11]([C@@H:13]3[CH2:15][C@H:14]3[C:16]3[CH:17]=[C:18]([CH:21]=[CH:22][CH:23]=3)[C:19]#[N:20])=[O:12])[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.C(N)(=[O:26])C>C1COCC1.O.[Pd](Cl)Cl>[CH:1]1([N:5]2[CH2:10][CH2:9][N:8]([C:11]([C@@H:13]3[CH2:15][C@H:14]3[C:16]3[CH:17]=[C:18]([CH:21]=[CH:22][CH:23]=3)[C:19]([NH2:20])=[O:26])=[O:12])[CH2:7][CH2:6]2)[CH2:2][CH2:3][CH2:4]1

Participants

6

Reactant 2

HCID 178AcetamideHCID 25196793HCID 25196793, compound

Product 1

HCID 25196902HCID 25196902, compoundYield 55.3%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

33C (180 mg, 0.58 mmol) was dissolved in THF (3 mL) and added to acetamide (687 mg, 11.64 mmol) and palladium(II) chloride (61.9 mg, 0.35 mmol) in H2O (1 mL). This suspension was left stirring at RT for 1 h then the temperature was increased to 50° C. and reaction stirred for 2 h. The reaction mixture was filtered on a Varian C18 reverse phase cartridge and the cartridge was washed with MeOH. The crude material was purified on preparative HPLC MS using the long high pH 25 to 45% gradient method (ACN in H2O ammonium carbonate buffer, 25 min.) on XBridge Prep C18 OBD, 30×150 mm, 5 mm, Waters reverse phase column. Evaporation of the desired pure fractions provided 105 mg 33D (55.1% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.28-1.39 (m, 1H) 1.63-1.79 (m, 3H) 1.80-1.96 (m, 2H) 1.97-2.13 (m, 3H) 2.32 (q, J=4.82 Hz, 4H) 2.56 (ddd, J=9.28, 5.76, 4.10 Hz, 1H) 2.65-2.83 (m, 1H) 3.54-3.77 (m, 4H) 5.58 (br. s., 1H) 6.07 (br. s., 1H) 7.30-7.43 (m, 2H) 7.52-7.61 (m, 2H), ES (M+H)+=328.3.

Workup

  1. waitThis suspension was left
  2. temperaturethe temperature was increased to 50° C.
  3. customreaction
  4. stirringstirred for 2 h
  5. filtrationThe reaction mixture was filtered on a Varian C18 reverse phase cartridge
  6. washthe cartridge was washed with MeOH
  7. customThe crude material was purified on preparative HPLC MS
  8. customgradient method (ACN in H2O ammonium carbonate buffer, 25 min.)
  9. customEvaporation of the desired pure fractions

Sources & evidence

ORD record
ord-3984a8a009134d0886692ee5b80b6203
Source dataset
uspto-grants-2011_11
Patent number
US08063215B2

Reaction notes

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