Water → HCID 25235778, compound

HRID 453000Notes

Reaction equation

HRID 453000 reaction equation
[NH2:1][C:2]1[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:30])[CH2:21][O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[CH:15][C:3]=1[C:4]([NH:6][CH:7]1[CH2:12][CH2:11][C:10](=[O:13])[NH:9][C:8]1=[O:14])=[O:5].C(OC)(OC)OC.[C:38]1(C)C=CC(S(O)(=O)=O)=C[CH:39]=1.O>CCOCC>[CH2:23]([O:22][CH2:21][C:20]([NH:19][C:16]1[CH:15]=[C:3]2[C:2](=[CH:18][CH:17]=1)[N:1]=[C:38]([CH3:39])[N:6]([CH:7]1[CH2:12][CH2:11][C:10](=[O:13])[NH:9][C:8]1=[O:14])[C:4]2=[O:5])=[O:30])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6101p-Toluenesulfonic acidHCID 9005Trimethyl orthoformateHCID 68728792HCID 68728792, compound

Product 1

HCID 25235778HCID 25235778, compoundYield 118.9%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

A solution of 2-amino-5-(2-benzyloxy-acetylamino)-N-(2,6-dioxo-piperidin-3-yl)-benzamide (0.26 g, 0.6 mmol) and trimethyl orthoformate (2 mL) and p-toluene sulfonic acid (60 mg) in acetonotrile (10 mL) was heated to reflux for 21 hours. To the mixture, was added water (25 mL) and ether (25 mL). The suspension was filtered and washed with water (50 mL) and ethyl acetate (50 mL) to give 2-benzyloxy-N-[3-(2,6-dioxo-piperidin-3-yl)-2-methyl-4-oxo-3,4-dihydro-quinazolin-6-yl]-acetamide as a white solid (180 mg, 72% yield): HPLC: Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 40/60 CH3CN/0.1% H3PO4, 2.87 min (99.3%); mp: 248-250° C.; 1H NMR (DMSO-d6) δ 2.14-2.16 (m, 1H, CHH), 2.62-2.87 (m, 3H, CH2, CHH), 4.15 (s, 2H, CH2), 4.64 (s, 2H, CH2), 5.49-5.50 (m, 1H, NCH), 7.31-7.41 (m, 5H, Ar), 7.68 (d, J=9 Hz, 1H, Ar), 8.06-8.10 (m, 1H, NH), 8.28 (s, 1H, CH), 8.55 (br, 1H, Ar), 10.24 (s, 1H, NH), 11.16 (s, 1H, NH; 13C NMR (DMSO-d6) δ 23.05, 31.48, 58 (br), 69.87, 72.92, 115.69, 122.15, 127.30, 128.16, 128.28, 128.34, 128.77, 137.98, 138.14, 144.06, 146.48, 160.10, 168.93, 170.43, 172.90; LCMS: MH=421; Anal Calcd for C22H20N4O5: C, 62.85; H, 4.79; N, 13.33. Found: C, 60.60; H, 4.29; N, 12.54.

Workup

  1. temperatureto reflux for 21 hours
  2. filtrationThe suspension was filtered
  3. washwashed with water (50 mL) and ethyl acetate (50 mL)

Sources & evidence

ORD record
ord-dc54215bdb914449bbe7c523c88a9697
Source dataset
uspto-grants-2013_07
Patent number
US08492395B2

Reaction notes

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