Hydrochloric Acid → HCID 56644526, 화합물

HRID 508406노트

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HRID 508406 반응식
[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]

참가 물질

12

반응물 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

생성물 1

HCID 56644526HCID 56644526, 화합물수율 9%

시약·촉매·용매 4

HCID 142844-(Dimethylamino)pyridine촉매HCID 679Dimethyl Sulfoxide용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매

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온도
80 °C

실험 절차

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%).

후처리

  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)

출처 및 근거

ORD 기록
ord-40166325006040a7b6c687dfdcf746e5
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09096500B2

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