1,1'-Carbonyldiimidazole → HCID 24964024, compound

HRID 1409648Notes

Reaction equation

HRID 1409648 reaction equation
[F:1][C:2]([F:14])([F:13])[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([OH:12])=O)=[CH:5][CH:4]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.Cl.[NH2:28][CH2:29][C:30]1[CH:39]=[CH:38][CH:37]=[C:36]2[C:31]=1[C:32](=[O:49])[N:33]([CH:41]1[CH2:46][CH2:45][C:44](=[O:47])[NH:43][C:42]1=[O:48])[C:34]([CH3:40])=[N:35]2>CN(C=O)C>[O:48]=[C:42]1[CH:41]([N:33]2[C:32](=[O:49])[C:31]3[C:36](=[CH:37][CH:38]=[CH:39][C:30]=3[CH2:29][NH:28][C:10](=[O:12])[CH2:9][C:6]3[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:14])[F:13])=[CH:8][CH:7]=3)[N:35]=[C:34]2[CH3:40])[CH2:46][CH2:45][C:44](=[O:47])[NH:43]1

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 118342(alpha,alpha,alpha-Trifluoro-4-tolyl)acetic acidHCID 249683051015474-47-1

Product 1

HCID 24964024HCID 24964024, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (4-trifluoromethyl-phenyl)-acetic acid (0.26 g, 1.3 mmol) in DMF (8 mL) in a 40° C. oil bath, was added 1,1′carbonyldiimidazole (0.22 g, 1.4 mmol) and stirred for one hour. To the mixture, 3-(5-aminomethyl-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione hydrogen chloride (0.42 g, 1.3 mmol) was added, and the mixture was stirred for 15 minutes. The solvent was evaporated, and the residue was purified by flash column chromatography (Silica gel, methanol/methylene chloride 4%/96%) to give N-[3-(2,6-dioxo-piperidin-3-yl)-2-methyl-4-oxo-3,4-dihydro-quinazolin-5-ylmethyl]-2-(4-trifluoromethyl-phenyl)-acetamide as an off-white solid (450 mg, 74% yield); HPLC, Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 mL/min, 240 nm, 10/90 CH3CN/0.1% H3PO4, grad. to 95/5 in 5 min, kept 5 min, 6.36 min (99.1%); mp, 199-201° C.; 1HNMR (DMSO-d6)2.14-2.19 (m, 1H, CHH), 2.57-2.87 (m, 6H, CHCH2, CH3), 3.66 (s, 2H, ArCH2), 4.75-4.86 (m, 2H, CH2NH), 5.24 (dd, J=6, 11 Hz, 1H, CH), 7.27-7.72 (m, 7H, Ar), 8.48 (t, J=6 Hz, 1H, CH2NH), 11.02 (s, 1H, NH); 13C NMR (DMSO-d6) δ 20.74, 23.28, 30.58, 41.75, 41.93, 56.48, 117.69, 124.72, 125.01 (d, JC-F=4 Hz), 125.01 (d, JC-F=10 Hz), 125.61, 129.91, 133.82, 140.58, 141.19, 148.45, 154.81, 160.90, 169.50, 169.54, 172.59. LCMS MH=487; Anal Calcd For C24H21N4O4F3: C, 57.76; H, 4.52; N, 11.23; F, 11.42. Found: C, 57.38; H, 4.49; N, 11.07; F, 11.64.

Workup

  1. stirringthe mixture was stirred for 15 minutes
  2. customThe solvent was evaporated
  3. customthe residue was purified by flash column chromatography (Silica gel, methanol/methylene chloride 4%/96%)

Sources & evidence

ORD record
ord-521b12e9b3fd407ba61da292777339fa
Source dataset
uspto-grants-2014_12
Patent number
US08921385B2

Reaction notes

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