1,1'-Carbonyldiimidazole → HCID 24964024, compound

HRID 1868271Notes

Reaction equation

HRID 1868271 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-d48528f803884719a74c4ea9bb0bfb62
Source dataset
uspto-grants-2009_12
Patent number
US07635700B2

Reaction notes

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