1,1'-Carbonyldiimidazole → HCID 65969733, compound

HRID 509501Notes

Reaction equation

HRID 509501 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.[NH2:25][CH:26]1[CH2:31][CH2:30][C:29](=[O:32])[NH:28][C:27]1=[O:33].C(=O)([O-])O.[Na+]>C(#N)C>[NH2:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([NH:25][CH:26]1[CH2:31][CH2:30][C:29](=[O:32])[NH:28][C:27]1=[O:33])=[O:6]

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 1345483-Aminopiperidine-2,6-dione hydrochlorideHCID 516892Sodium BicarbonateHCID 27249674-Fluoroanthranilic acid

Product 1

HCID 65969733HCID 65969733, compoundYield 47.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 2-amino-4-fluorobenzoic acid (2.5 g, 16 mmol) and CDI (2.4 g, 15 mmol) in acetonitrile (30 mL) was stirred at room temperature for 1.5 hours. To the suspension, was added 3-amino-piperidine-2,6-dione hydrogen chloride (2.4 g, 15 mmol) and sodium hydrogen carbonate (1.6 g, 19 mmol), and the mixture was heated at 50° C. for 21 hours. The suspension was cooled to room temperature for 1 hour. The suspension was filtered and washed with acetonitrile (5 mL) and water (2×20 mL). The solid was stirred in methanol (15 mL) overnight. The suspension was filtered and washed with methanol (15 mL) to give 2-amino-N-(2,6-dioxo-piperidin-3-yl)-4-fluorobenzamide as an off-white solid (1.9 g, 45% yield): 1H NMR (DMSO-d6) δ 1.91-1.96 (m, 1H, CHH), 2.04-2.18 (m, 1H, CHH), 2.50-2.56 (m, 1H, CHH), 2.73-2.85 (m, 1H, CHH), 4.67-4.76 (m, 1H, NCH), 6.35 (dt, J=2, 9 Hz, 1H, Ar), 6.48 (dd, J=2, 12 Hz, 1H, Ar), 6.76 (brs, 2H. NH2), 7.58 (dd; J=7, 8 Hz, 1H, Ar), 8.50 (d, J=8 Hz, 1H, NH), 10.84 (s, 1H, NH); 13C NMR (DMSO-d6) δ 24.06, 30.91, 48.98, 101.30 (d, JC-F=23 Hz), 101.60 (d, JC-F=22 Hz), 110.60, 130.66 (d, JC-F=11 Hz), 152.16 (d, JC-F=12 Hz), 164.46 (d. JC-F=246 Hz), 167.80, 172.30, 172.94.

Workup

  1. temperaturethe mixture was heated at 50° C. for 21 hours
  2. temperatureThe suspension was cooled to room temperature for 1 hour
  3. filtrationThe suspension was filtered
  4. washwashed with acetonitrile (5 mL) and water (2×20 mL)
  5. stirringThe solid was stirred in methanol (15 mL) overnight
  6. filtrationThe suspension was filtered
  7. washwashed with methanol (15 mL)

Sources & evidence

ORD record
ord-7c063a55c3fa40c88e58d0d8e359f843
Source dataset
uspto-grants-2015_08
Patent number
US09096573B2

Reaction notes

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