Formamidine acetate → HCID 58529955, compound

HRID 1972752Notes

Reaction equation

HRID 1972752 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH2:14][C@@H:13]([C:17]2[N:18]([NH2:24])[C:19](C#N)=[CH:20][CH:21]=2)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:25](O)(=O)C.[CH:29]([NH2:31])=[NH:30]>CCCCO>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH2:14][C@@H:13]([C:17]2[N:18]3[C:19]([C:29]([NH2:31])=[N:30][CH:25]=[N:24]3)=[CH:20][CH:21]=2)[CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 160693Formamidine acetate2×HCID 58529376HCID 58529376, compound

Product 1

HCID 58529955HCID 58529955, compoundYield 93.1%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

The product from step 5 (3.57 g, 11.00 mmol) was dissolved in 40 mL of n-BuOH and treated with formamidine acetate (11.48 g, 110.0 mmol). The mixture was heated to reflux for 8 h whereupon an additional 2.75 g (26.4 mmol) of formamidine acetate was added. Heating continued for 1.5 h and then the reaction was allowed to cool to rt overnight. The black reaction mixture was filtered through Celite® and the Celite® pad was washed with 100 mL of EtOH. The filtrate was concentrated in vacuo and the residue was partitioned between water (100 mL) and 3×75 mL of EtOAc. The combined organic extracts were washed with water, 2M aq. Na2CO3, brine, dried over Na2SO4 and filtered through a 1″ (d) by 4″ (w) pad of SiO2 (pre-wetted with EtOAc) and the pad was washed with ˜500 mL of EtOAc. The filtrate was concentrated in vacuo and the residue dried in a vacuum oven at 40° C. for 2 h to give the title compound as a yellowish brown solid (3.60 g). 1H NMR (300 MHz, CD3OD) δ 7.82 (s, 1H), 7.64 (bs, 2H), 7.42-7.24 (m, 5H), 6.81 (d, 1H), 6.44 (d, 1H), 5.08 (bs, 2H), 4.2 (d, 1H), 3.96 (d, 1H), 3.23 (m, 1H), 3.16-2.84 (m, 2H), 2.03, (m, 1H), 1.79-1.62 (m, 2H), 1.46 (m, 1H). ES-MS m/z 352.2 [M+H]+, HPLC RT (min) 2.49.

Workup

  1. temperatureThe mixture was heated
  2. additionwas added
  3. temperatureHeating
  4. customThe black reaction mixture
  5. filtrationwas filtered through Celite®
  6. washthe Celite® pad was washed with 100 mL of EtOH
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was partitioned between water (100 mL) and 3×75 mL of EtOAc
  9. washThe combined organic extracts were washed with water, 2M aq. Na2CO3, brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered through a 1″ (d) by 4″ (w) pad of SiO2 (pre-wetted with EtOAc)
  12. washthe pad was washed with ˜500 mL of EtOAc
  13. concentrationThe filtrate was concentrated in vacuo
  14. customthe residue dried in a vacuum oven at 40° C. for 2 h

Sources & evidence

ORD record
ord-f55b2376b3bd4be3bf2e4e1c9cc7ad9c
Source dataset
uspto-grants-2013_04
Patent number
US08431695B2

Reaction notes

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