3-Chloro-4-methylbenzoic Acid → 3-chloro-N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-4-methyl-benzamide

HRID 448463노트

반응식

HRID 448463 반응식
Cl.[NH2:2][CH2:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[C:6](=[O:22])[N:7]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[C:8]2=[O:13].N12CCCN=C1CCCCC2.[Cl:34][C:35]1[CH:36]=[C:37]([CH:41]=[CH:42][C:43]=1[CH3:44])[C:38](O)=[O:39].Cl.CN(C)CCCN=C=NCC>CC#N>[Cl:34][C:35]1[CH:36]=[C:37]([CH:41]=[CH:42][C:43]=1[CH3:44])[C:38]([NH:2][CH2:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[C:6](=[O:22])[N:7]([CH:14]1[CH2:19][CH2:18][C:17](=[O:20])[NH:16][C:15]1=[O:21])[C:8]2=[O:13])=[O:39]

참가 물질

6

반응물 4

HCID 788403-Chloro-4-methylbenzoic AcidHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 219885254-(aminomethyl)-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione hydrochloride

생성물 1

HCID 588273293-chloro-N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-4-methyl-benzamide수율 79%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

To a stirred suspension of 4-aminomethyl-2-(2,6-dioxo-piperidin-3-yl)-isoindole-1,3-dione hydrochloride (0.7 g, 2.2 mmol) in CH3CN (60 ml), was added 1,8-diazabicyclo[5.4.0]undec-7-ene (0.8 g, 5.4 mmol). After stirring for 10 minutes, 1-hydroxybenzenetriazole (0.35 g, 2.6 mmol) and 3-chloro-4-methyl-benzoic acid (0.4 g, 2.4 mmol) were added. To the reaction mixture, was then added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.62 g, 3.2 mmol), and the mixture was stirred at room temperature overnight. The reaction mixture was then concentrated in vacuo, and the residue was stirred in H2O (50 mL). A suspension formed and after filtration the solid was reslurried in acetone (20 mL). The suspension was filtered to afford 3-chloro-N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-4-methyl-benzamide as a white solid (0.75 g, 79%): mp, 249-251° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=6.8 min. (97%); 1H NMR (DMSO-d6): δ 2.06-2.11 (m, 1H), 2.39 (s, 3H), 2.53-2.64 (m, 2H), 2.85-2.96 (m, 1H), 4.94 (d, J=5.8 Hz, 2H), 5.15-5.20 (dd, J=5, 12 Hz, 1H), 7.47-7.97 (m, 6H), 7.82-7.89 (m, 3H), 9.22 (t, J=6 Hz, 1H), 11.15 (s, 1H). 13C NMR (DMSO-d6) δ: 19.55, 21.97, 30.92, 38.36, 48.86, 121.89, 126.07, 127.15, 127.60, 131.22, 131.52, 133.11, 133.33, 134.80, 139.06, 139.10, 165.13, 166.94, 167.50, 169.81, 172.74. Anal Calcd for C22H18ClN3O5: C, 60.08; H, 4.12; N, 9.55; Cl, 8.06. Found: C, 59.69; H, 4.15; N, 9.60; Cl, 8.08.

후처리

  1. concentrationThe reaction mixture was then concentrated in vacuo
  2. stirringthe residue was stirred in H2O (50 mL)
  3. customA suspension formed
  4. filtrationafter filtration the solid
  5. filtrationThe suspension was filtered

출처 및 근거

ORD 기록
ord-c32f1e345e5c44a5a74219db35f77a9e
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08481568B2

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