Acetic Acid → HCID 68728792, compound

HRID 509461Notes

Reaction equation

HRID 509461 reaction equation
[NH2:1][C:2]1[CH:13]=[C:6]2[C:7]([O:9]C(=O)[NH:11][C:5]2=[CH:4][CH:3]=1)=O.C(N(CC)CC)C.[CH2:21]([O:28][CH2:29][C:30](Cl)=[O:31])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.Cl.[NH2:34][CH:35]1[CH2:40][CH2:39][C:38](=[O:41])[NH:37][C:36]1=[O:42].C(O)(=O)C>O>[NH2:11][C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:30](=[O:31])[CH2:29][O:28][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[CH:13][C:6]=1[C:7]([NH:34][CH:35]1[CH2:40][CH2:39][C:38](=[O:41])[NH:37][C:36]1=[O:42])=[O:9]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 8471Triethylamine2×HCID 1345483-Aminopiperidine-2,6-dione hydrochlorideHCID 177085Benzyloxyacetyl chlorideHCID 27353536-Amino-2-hydroxy-4H-3,1-benzoxazin-4-one

Product 1

HCID 68728792HCID 68728792, compoundYield 12.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred mixture of 5-amino-isatoic anhydride (1.0 g, 5.6 mmol) and triethyl amine (0.8 mL, 9.0 mmol) in acetronitrile (15 mL), was added benzyloxyacetyl chloride (0.87 mL, 5.6 mmol) dropwise at room temperature. The mixture was kept at room temperature overnight. To the mixture, was added triethylamine (3.1 mL, 22 mmol), 3-amino-piperidine-2,6-dione hydrogen chloride (0.92 g, 5.6 mmol), and acetic acid (3.2 mL, 56 mmol). The mixture was heated at 80° C. for 8 hours. To the mixture, was added water (75 mL). The suspension was filtered and washed with water (75 mL) and ethyl acetate (75 mL) to give a dark solid, which was purified with column chromatography (Silica Gel, methanol/methylene chloride 0% to 10% in 15 min) to give 2-amino-5-(2-benzyloxy-acetylamino)-N-(2,6-dioxo-piperidin-3-yl)-benzamide as a white solid (0.28 g, 12% yield): 1H NMR (DMSO-d6) δ 1.92-2.18 (m, 2H, 2CHH), 2.50-2.55 (m, 1H, CHH), 2.72-2.84 (m, 1H, CHH), 4.03 (s, 2H, CH2), 4.61 (s, 2H, CH2), 4.68-4.77 (m, 1H, NCH), 6.19 (br, 2H, NH2), 6.68 (d, J=9 Hz, 1H, Ar), 7.30-7.42 (m, 6H, Ar), 7.62 (d, J=2 Hz, 1H, Ar), 8.43 (d, J=8 Hz, 1H, NH), 9.44 (s, 1H, NH), 10.84 (s, 1H, NH); 13C NMR (DMSO-d6) δ 24.09, 30.96, 49.12, 69.37, 72.35, 114.27, 116.23, 121.11, 125.99, 126.13, 127.64, 127.77, 128.27, 137.68, 146.19, 167.28, 168.36, 172.35, 173.01.

Workup

  1. filtrationThe suspension was filtered
  2. washwashed with water (75 mL) and ethyl acetate (75 mL)
  3. customto give a dark solid, which
  4. customwas purified with column chromatography (Silica Gel, methanol/methylene chloride 0% to 10% in 15 min)

Sources & evidence

ORD record
ord-46e08682dcb344148e8461e5af648084
Source dataset
uspto-grants-2015_08
Patent number
US09096573B2

Reaction notes

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