Methanol → HCID 89813910, compound

HRID 525361Notes

Reaction equation

HRID 525361 reaction equation
[C:1]1([CH:7]2[C:11]3([CH2:15][CH2:14][CH2:13][CH2:12]3)[O:10][C:9](=[O:16])[NH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.I[C:18]1[CH:36]=[CH:35][C:21]([C:22]([NH:24][C:25]2[CH:26]=[CH:27][CH:28]=[C:29]3[C:34]=2[N:33]=[CH:32][CH:31]=[CH:30]3)=[O:23])=[CH:20][CH:19]=1.C(=O)([O-])[O-].[K+].[K+].CO>CN(C=O)C.C(Cl)Cl.[Cu]I>[O:16]=[C:9]1[N:8]([C:18]2[CH:36]=[CH:35][C:21]([C:22]([NH:24][C:25]3[CH:26]=[CH:27][CH:28]=[C:29]4[C:34]=3[N:33]=[CH:32][CH:31]=[CH:30]4)=[O:23])=[CH:20][CH:19]=2)[CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:11]2([CH2:15][CH2:14][CH2:13][CH2:12]2)[O:10]1

Participants

8

Reactant 4

HCID 887MethanolHCID 11430Potassium CarbonateHCID 41661718HCID 41661718, compoundHCID 89813819HCID 89813819, compound

Product 1

HCID 89813910HCID 89813910, compoundYield 11%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

To a 50 mL dried round bottom flask containing a degassed solution of 4-phenyl-1-oxa-3-azaspiro[4.4]nonan-2-one (1 eq., 1.73 mmol) and 4-iodo-N-(quinolin-8-yl)benzamide (1.2 eq.) in DMF (15 mL), potassium carbonate (2.5 eq.) and trans (N,N)-dimethyl cyclohexanediamine (0.5 eq.) was added CuI (0.1 eq). The resulting mixture was stirred at 120° C. for 15 hours. Reaction progress was monitored by TLC (TLC eluent: 10% MeOH in DCM). The reaction mixture was cooled and poured into crushed ice (5 g). The solid thus obtained was filtered, washed with water (25 mL) and dissolved in DCM. The DCM solution was then washed with water (100 mL), washed brine (50 mL) and dried over anhydrous Na2SO4, filtered, concentrated and purified by column chromatography using silica gel and DCM as eluting solvent to yield (R+S) 4-(2-oxo-4-phenyl-1-oxa-3-azaspiro[4.4]nonan-3-yl)-N-(quinolin-8-yl)benzamide (90 mg, 11%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 10.55 (s, 1H), 8.94 (d, J=4 Hz, 1H), 8.65 (d, J=7.2 Hz, 1H), 8.44 (d, J=8.4 Hz, 1H), 7.95 (d, J=8.4 Hz, 1H), 7.75-7.63 (m, 5H), 7.39-7.32 (m, 5H), 5.75 (s, 1H), 2.10-2.20 (m, 2H), 1.50-1.78 (s, 4H), 1.30-1.40 (m, 1H), 1.10-1.20 (m, 1H). m/z (ESI) 464.3 (M+H)+.

Workup

  1. customTo a 50 mL dried round bottom flask
  2. customReaction progress
  3. temperatureThe reaction mixture was cooled
  4. additionpoured
  5. customThe solid thus obtained
  6. filtrationwas filtered
  7. washwashed with water (25 mL)
  8. dissolutiondissolved in DCM
  9. washThe DCM solution was then washed with water (100 mL)
  10. washwashed brine (50 mL)
  11. dry with materialdried over anhydrous Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. custompurified by column chromatography
  15. washas eluting solvent

Sources & evidence

ORD record
ord-1e5ead490aac4e089fd784ffaa0a84ff
Source dataset
uspto-grants-2016_05
Patent number
US09340549B2

Reaction notes

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