2-(4-Fluorophenyl)acetic acid → HCID 58827273, 화합물

HRID 448473노트

반응식

HRID 448473 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.[F:34][C:35]1[CH:40]=[CH:39][C:38]([CH2:41][C:42](O)=[O:43])=[CH:37][CH:36]=1.Cl.CN(C)CCCN=C=NCC>CC#N>[O:21]=[C:15]1[CH:14]([N:7]2[C:6](=[O:22])[C:5]3[C:9](=[CH:10][CH:11]=[CH:12][C:4]=3[CH2:3][NH:2][C:42](=[O:43])[CH2:41][C:38]3[CH:39]=[CH:40][C:35]([F:34])=[CH:36][CH:37]=3)[C:8]2=[O:13])[CH2:19][CH2:18][C:17](=[O:20])[NH:16]1

참가 물질

6

반응물 4

HCID 98372-(4-Fluorophenyl)acetic 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 58827273HCID 58827273, 화합물수율 68.7%

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 (0.70 g, 2.2 mmol) in CH3CN (60 ml), was added 1,8-diazabicyclo[5.4.0]undec-7-ene (0.82 g, 5.4 mmol). After stirring for 10 minutes, 1-hydroxybenzenetriazole (0.35 g, 2.6 mmol) and 4-fluorophenylacetic acid (0.37 g, 2.4 mmol) were added, followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.62 g, 3.2 mmol). After stirring at room temperature overnight and was then concentrated in vacuo, and the residue was dissolved in CH2Cl2 (50 mL). The CH2Cl2 solution was washed with water (2×30 mL) and brine (30 mL), and dried over MgSO4. The organic solvent was removed in vacuo, and the resulting oil was purified by ISCO silica gel flash chromatography (eluent: 0% MeOH in CH2Cl2 to 5% MeOH in 10 min then stay at this ratio for 15 min) to afford N-[2-(2,6-dioxo-piperidin-3-yl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-2-(4-fluoro-phenyl)-acetamide as a white solid (0.64 g, 65%): mp, 214-216° C.; HPLC: Waters Symmetry C-18, 3.9×150 mm, 5 micro, 1 mL/min, 240 nm, 40/60 (CH3CN/H2O): tR=3.0 min (99%); 1H NMR (DMSO-d6): δ 2.03-2.08 (m, 1H), 2.51-2.63 (m, 2H), 2.86-2.91 (m, 1H), 3.53 (s, 2H), 4.72 (d, J=6.0 Hz, 2H), 5.12-5.18 (dd, J=5, 12 Hz, 1H), 7.10-7.16 (m, 2H), 7.29-7.34 (m, 2H), 7.62-7.65 (m, 1H), 7.78-7.81 (m, 2H), 8.67 (t, J=5.9 Hz, 1H), 11.14 (s, 1H). 13C NMR (DMSO-d6) δ: 21.95, 30.90, 37.83, 41.17, 48.82, 114.77, 115.05, 121.89, 127.12, 130.81, 130.92, 131.51, 132.24, 132.28, 133.19, 134.67, 139.09, 159.42, 162.62, 166.90, 167.42, 169.78, 170.51, 172.73. Anal Calcd for C22H18FN3O5: C, 62.41; H, 4.29; N, 9.92; F, 4.49. Found: C, 62.05; H, 4.18; N, 9.85; F, 4.48.

후처리

  1. stirringAfter stirring at room temperature overnight
  2. concentrationwas then concentrated in vacuo
  3. dissolutionthe residue was dissolved in CH2Cl2 (50 mL)
  4. washThe CH2Cl2 solution was washed with water (2×30 mL) and brine (30 mL)
  5. dry with materialdried over MgSO4
  6. customThe organic solvent was removed in vacuo
  7. customthe resulting oil was purified by ISCO silica gel flash chromatography (eluent
  8. wait0% MeOH in CH2Cl2 to 5% MeOH in 10 min then stay at this ratio for 15 min

출처 및 근거

ORD 기록
ord-9471b08bc2a24e8d9f007a84f0bb18eb
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08481568B2

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