Hydrochloric Acid → HCID 59696213, compound

HRID 2075289Notes

Reaction equation

HRID 2075289 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([C:28]([OH:30])=O)=[N:11][C:12]([I:27])=[C:13]2[C:18]=1[N:17]=[CH:16][C:15]([CH2:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=1)=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.ON1C2C=CC=CC=2N=N1.[CH3:41][O:42][CH2:43][CH2:44][NH2:45].Cl.C(N=C=NCCCN(C)C)C.Cl>ClCCl>[CH3:41][O:42][CH2:43][CH2:44][NH:45][C:28]([C:10]1[C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[C:18]2[C:13]([CH:14]=[C:15]([CH2:19][C:20]3[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=3)[CH:16]=[N:17]2)=[C:12]([I:27])[N:11]=1)=[O:30]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 80182-MethoxyethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 23149774HCID 23149774, compound

Product 1

HCID 59696213HCID 59696213, compoundYield 81.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To the above Compound 9 (7.0 g, 13.6 mmol), 1-hydroxybenzotriazole (208 mg, 1.36 mmol) was added dichloromethane (75 ml) to give suspension, and was added 2-methoxyethyl amine (1.42 ml, 16.3 mmol) in nitrogen gas flow under stirring on ice, followed by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (3.13 g, 16.3 mmol). 30 minutes later, the solution was stirred at room temperature. After 3 hours, the reaction solution was subjected to distillation under reduced pressure, and to the residue (12 g) was added and solved ethyl acetate (150 ml) and water (100 ml), and followed by 2N hydrochloric acid aqueous solution (5.7 ml, 11.4 mmol). Then the solution was shaken for separation, washed once with water and with sodium chloride aqueous solution, dried over sodium sulfate and subjected to distillation under reduced pressure. The resultant residue (7.97 g) was solved in methanol (5 ml), and added with diisopropyl ether (35 ml) little by little under warming and left at room temperature. Then the product was collected by filtering and washed with diisopropyl ether, to give Compound 10 (6.31 g, 81.1%). The filtrate was subjected to silica gel silica gel chromatography, to give 8-benzyloxy-3-(4-fluorobenzyl)-5-iodo[1,6]naphthyridine-7-carboxylic acid (2-methoxyethyl)amide 10 (437 mg, 5.6%).

Workup

  1. customto give suspension
  2. stirring30 minutes later, the solution was stirred at room temperature
  3. distillationthe reaction solution was subjected to distillation under reduced pressure
  4. additionto the residue (12 g) was added
  5. stirringThen the solution was shaken for separation
  6. washwashed once with water and with sodium chloride aqueous solution
  7. dry with materialdried over sodium sulfate
  8. distillationsubjected to distillation under reduced pressure
  9. additionadded with diisopropyl ether (35 ml) little by little
  10. temperatureunder warming
  11. waitleft at room temperature
  12. customThen the product was collected
  13. filtrationby filtering
  14. washwashed with diisopropyl ether

Sources & evidence

ORD record
ord-e496e90bb4f2435f8cb098003e45f04c
Source dataset
uspto-grants-2011_04
Patent number
US07919623B2

Reaction notes

Loading…