Benzoic Acid → HCID 10223647, compound

HRID 1823308Notes

Reaction equation

HRID 1823308 reaction equation
C([O:8][C:9](=O)[NH:10][CH2:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH:14]([N:18]2[C:27]3[C:22](=[N:23][CH:24]=[CH:25][CH:26]=3)[C:21]3=[N:28][O:29][C:30]([CH3:31])=[C:20]3[C:19]2=[O:32])[CH2:13]1)C1C=CC=CC=1.I[Si](C)(C)C.C(O)(=O)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>ClCCl.CN(C)C=O>[CH3:31][C:30]1[O:29][N:28]=[C:21]2[C:22]3[C:27](=[CH:26][CH:25]=[CH:24][N:23]=3)[N:18]([CH:14]3[CH2:15][CH2:16][CH2:17][CH:12]([CH2:11][NH:10][C:9](=[O:8])[C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=4)[CH2:13]3)[C:19](=[O:32])[C:20]=12

Participants

9

Reactant 6

HCID 243Benzoic AcidHCID 81531DiisopropylethylamineHCID 85247Trimethylsilyl iodideHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 69652693HCID 69652693, compound

Product 1

HCID 10223647HCID 10223647, compoundYield 80.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Dissolve [3-(3-methyl-4-oxo-5H-2-oxa-1,5,9-triaza-cyclopenta[a]naphthalen-5yl)-cyclohexylmethyl]-carbamic acid benzyl ester (130 mg, 0.29 mmol) in dry dichloromethane (5 mL). Add iodotrimethylsilane (0.11 mL, 0.77 mmol) and stir overnight at ambient temperature. Quench with methanol (5 mL) and concentrate in vacuo. Dissolve in minimal dichloromethane and add excess diethyl ether. Decant and dry the dark solid crude amine salt in vacuo and use directly without purification. MS(ES): (M+1)+ 313.1, 314.1 m/z. Combine this amine salt with benzoic acid (36 mg, 0.29 mmol),1-[3-(dimethylamino)-propyl]-3-ethylcarbodiimide hydrochloride (56 mg, 0.29 mmol), 1-hydroxy-7-azabenzo-triazole (40 mg, 0.29 mmol), and N,N-diisopropylethyl amine (0.20 mL, 1.15 mmol), in N,N-dimethylformamide (5 mL) and stir overnight at ambient temperature. Concentrated in vacuo and take up in water and extract with dichloromethane. Dry over sodium sulfate and concentrate in vacuo. Elute over silica gel using methanoldichloromethane to give 97 mg (80%) of the desired product as a light tan solid. MS(ES): (M+1)+ 417.1, 418.1 m/z.

Workup

  1. customQuench with methanol (5 mL)
  2. concentrationconcentrate in vacuo
  3. dissolutionDissolve in minimal dichloromethane
  4. additionadd excess diethyl ether
  5. customDecant
  6. dry with materialdry the dark solid crude amine salt in vacuo and use
  7. customdirectly without purification
  8. concentrationConcentrated in vacuo
  9. extractionextract with dichloromethane
  10. dry with materialDry over sodium sulfate
  11. concentrationconcentrate in vacuo
  12. washElute over silica gel using methanoldichloromethane

Sources & evidence

ORD record
ord-bbe816a624a14702a7c99533ccf2183a
Source dataset
uspto-grants-2006_05
Patent number
US07037921B2

Reaction notes

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