Hydrochloric Acid → HCID 11752505, compound

HRID 1713352Notes

Reaction equation

HRID 1713352 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([CH3:35])[C:9]=1[C:10]#[C:11][CH2:12][C:13]([OH:34])([CH2:18][C:19]1([CH3:33])[C:28]2[C:23](=[CH:24][CH:25]=[C:26]([S:29]([CH3:32])(=[O:31])=[O:30])[CH:27]=2)[O:22][CH2:21][CH2:20]1)[C:14]([F:17])([F:16])[F:15])[C:5]#[N:6].FC(F)(F)C(OC(=O)C(F)(F)F)=O.CN(C)C(=N)N(C)C.Cl>ClCCl>[CH3:35][C:8]1[CH:7]=[C:4]([C:5]#[N:6])[CH:3]=[C:2]2[C:9]=1[CH:10]=[C:11]([CH2:12][C:13]([OH:34])([CH2:18][C:19]1([CH3:33])[C:28]3[C:23](=[CH:24][CH:25]=[C:26]([S:29]([CH3:32])(=[O:31])=[O:30])[CH:27]=3)[O:22][CH2:21][CH2:20]1)[C:14]([F:17])([F:15])[F:16])[NH:1]2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 9845Trifluoroacetic anhydrideHCID 664601,1,3,3-TetramethylguanidineHCID 59463787HCID 59463787, compound

Product 1

HCID 11752505HCID 11752505, compoundYield 8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
140 °C

Procedure

To a chilled (0° C.) solution of 130 mg (0.25 mmol) of 3-amino-5-methyl-4-[5,5,5-trifluoro-4-hydroxy-4-(6-methanesulfonyl-4-methylchroman-4-ylmethyl)pent-1-ynyl]benzonitrile in 5 mL of dichloromethane was added 105 μL (0.74 mmol) of trifluoroacetic anhydride. After 15 minutes, the reaction was concentrated in vacuo and the residue was diluted with diethyl ether and concentrated in vacuo, three times. The resulting oil was dissolved in 1 mL of DMSO and then 0.09 mL (0.74 mmol) of tetramethylguanidine was added and the mixture was warmed at 140° C. in a microwave oven. After 10 minutes, the mixture was cooled, poured onto crushed ice with 1N aqueous HCl and extracted with ethyl acetate. The combined organic fractions were dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by preparatory TLC (silica gel, 1:1 ethyl acetate-hexanes) to afford first 35 mg (27%) of the title compound as a single diastereomer (M−1=505) and second 10 mg (8%) of the title compound as the opposite diastereomer (M−1=505).

Workup

  1. concentrationthe reaction was concentrated in vacuo
  2. additionthe residue was diluted with diethyl ether
  3. concentrationconcentrated in vacuo, three times
  4. dissolutionThe resulting oil was dissolved in 1 mL of DMSO
  5. waitAfter 10 minutes
  6. temperaturethe mixture was cooled
  7. additionpoured
  8. extractionextracted with ethyl acetate
  9. dry with materialThe combined organic fractions were dried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified by preparatory TLC (silica gel, 1:1 ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-a29fd0e84d204a4b93c92eead38a2afe
Source dataset
uspto-grants-2010_09
Patent number
US07795272B2

Reaction notes

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