Benzoic Acid → HCID 25106076, compound

HRID 1397495Notes

Reaction equation

HRID 1397495 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([C:13]3([O:17][CH2:18][C:19]([O:21]C)=[O:20])[CH2:16][CH2:15][CH2:14]3)=[N:10][CH:9]=2)=[CH:4][CH:3]=1.[C:23](O)(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.CN1CCOCC1.[OH-].[Na+]>C(OCC)(=O)C.O.CN(C)C=O>[C:23]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[S:12][C:11]([C:13]3([O:17][CH2:18][C:19]([OH:21])=[O:20])[CH2:14][CH2:15][CH2:16]3)=[N:10][CH:9]=2)=[CH:6][CH:7]=1)(=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

Participants

10

Reactant 6

HCID 243Benzoic AcidHCID 79724-MethylmorpholineHCID 14798Sodium HydroxideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 68720623HCID 68720623, compound

Product 1

HCID 25106076HCID 25106076, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A N,N-dimethylformamide (1 mL) solution of Example 24B (0.025 g, 0.079 mmol), benzoic acid (0.011 g, 0.087 mmol), 1-ethyl-3-[3-(dimethylamino)propyl]-carbodiimide hydrochloride (0.015 g, 0.079 mmol), 1-hydroxybenzotriazole hydrate (0.011 g, 0.079 mmol), and N-methylmorpholine (0.345 mL, 0.314 mmol) was heated to 55° C. for 16 h. The solution was cooled to room temperature and diluted with ethyl acetate (2 mL) and H2O (2 mL). The layers were separated, and the organic was washed with brine (1×1 mL), dried with anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was dissolved in methanol (2 mL) and 2.5M NaOH (0.95 mL, 0.237 mmol) was added. The reaction was stirred at room temperature for 16 h, concentrated under reduced pressure, and purified by RP-HPLC (preparative reversed-phase high pressure liquid chromatography) using a Zorbax SB-C18 7M 21.2×250 mm column with UV detection analyzed at 220 and 254 nM (preparative method: water with 0.1% trifluoroacetic acid and CH3CN with 0.1% trifluoroacetic acid gradient 5-95% CH3CN over 30 minutes at 15 mL/min) to provide the title compound as a white solid. 1H NMR (300 MHz, METHANOL-d4) δ ppm 1.83-1.93 (m, 1 H), 1.95-2105 (m, 1 H), 2.53-2.67 (m, 5 H), 3.99 (s, 2 H), 7.49-7.60 (m, 4 H), 7.63-7.67 (m, 2 H) 7.81 (m, 2 H), 7.92-7.94 (m, 2 H), 7.97 (s, 1 H); MS (ESI) m/z 409 [M+H]+.

Workup

  1. customThe layers were separated
  2. washthe organic was washed with brine (1×1 mL)
  3. dry with materialdried with anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe residue was dissolved in methanol (2 mL)
  7. concentrationconcentrated under reduced pressure
  8. custompurified by RP-HPLC (preparative reversed-phase high pressure liquid chromatography)
  9. customanalyzed at 220 and 254 nM (preparative method: water with 0.1% trifluoroacetic acid and CH3CN with 0.1% trifluoroacetic acid gradient 5-95% CH3CN over 30 minutes at 15 mL/min)

Sources & evidence

ORD record
ord-94b9ba8203624386af6d09686a17115b
Source dataset
uspto-grants-2014_12
Patent number
US08901152B2

Reaction notes

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