Hydrochloric Acid → HCID 56644526, compound

HRID 508406Notes

Reaction equation

HRID 508406 reaction equation
[C:1]1([CH2:11][OH:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.CC(C)([O-])C.[K+].[C:19]([C:21]1[CH:22]=[C:23]([CH:28]=[CH:29][C:30]=1F)[C:24](OC)=[O:25])#[N:20].[OH-].[Li+].Cl.[CH3:35][S:36]([NH2:39])(=[O:38])=[O:37].Cl.CN(C)CCCN=C=NCC>O1CCCC1.CS(C)=O.CN(C)C1C=CN=CC=1.ClCCl>[C:19]([C:21]1[CH:22]=[C:23]([CH:28]=[CH:29][C:30]=1[O:12][CH2:11][C:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1)[C:24]([NH:39][S:36]([CH3:35])(=[O:38])=[O:37])=[O:25])#[N:20]

Participants

12

Reactant 7

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 209081-NaphthalenemethanolHCID 72879MethanesulfonamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 23665647Potassium tert-butoxideHCID 45790123Methyl 3-cyano-4-fluorobenzoate

Product 1

HCID 56644526HCID 56644526, compoundYield 9%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 1-naphthylmethanol (19.8 mg, 0.13 mmol) in anhydrous tetrahydrofuran were added potassium tert butoxide (0.14 mL, 1 M solution in anhydrous tetrahydrofuran 0.14 mmol) followed by a solution of methyl 3-cyano-4-fluorobenzoate (22.4 mg, 0.13 mmol) in dimethylsulfoxide (0.1 mL). The reaction mixture was shaken at 80° C. for 16 hours, evaporated in vacuo, and water (1 mL) was added. The mixture was extracted with ethyl acetate (3×1 mL) and the combined organic extracts were dried over anhydrous sodium sulphate, filtered and evaporated in vacuo. The residue was dissolved in tetrahydrofuran (0.7 mL), an aqueous solution of lithium hydroxide (0.7 mL, 1 M, 0.70 mmol) added and the mixture was shaken at 60° C. for 2 hours. The reaction mixture was evaporated in vacuo and hydrochloric acid (0.70 mL, 1 M, 0.70 mmol) was added. The resulting mixture was extracted with ethyl acetate (3×1 mL) and the combined organic extracts were dried over anhydrous sodium sulphate, filtered and evaporated in vacuo. To the residue were added methanesulfonamide (27 mg, 0.28 mmol), a solution of 4-dimethylaminopyridine (24.4 mg, 0.20 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (38.3 mg, 0.20 mmol) in dichloromethane (1 mL). The mixture was shaken for 16 hours at 30° C. and then evaporated in vacuo. The residue was purified on an HPLC column (Grace Vydac C18 200*20 mm*5 mm column) with a gradient of acetonitrile/water (0.1% trifluoroacetic acid) to yield the title compound (4.25 mg, 9%).

Workup

  1. customevaporated in vacuo, and water (1 mL)
  2. additionwas added
  3. extractionThe mixture was extracted with ethyl acetate (3×1 mL)
  4. dry with materialthe combined organic extracts were dried over anhydrous sodium sulphate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. dissolutionThe residue was dissolved in tetrahydrofuran (0.7 mL)
  8. stirringthe mixture was shaken at 60° C. for 2 hours
  9. additionwas added
  10. extractionThe resulting mixture was extracted with ethyl acetate (3×1 mL)
  11. dry with materialthe combined organic extracts were dried over anhydrous sodium sulphate
  12. filtrationfiltered
  13. customevaporated in vacuo
  14. stirringThe mixture was shaken for 16 hours at 30° C.
  15. customevaporated in vacuo
  16. customThe residue was purified on an HPLC column (Grace Vydac C18 200*20 mm*5 mm column) with a gradient of acetonitrile/water (0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-40166325006040a7b6c687dfdcf746e5
Source dataset
uspto-grants-2015_08
Patent number
US09096500B2

Reaction notes

Loading…