Phthalimide → 2-[(3-Chloropyrazin-2-yl)-quinolin-7-ylmethyl]-isoindole-1,3-dione

HRID 244104

반응식

HRID 244104 반응식
[Cl:1][C:2]1[C:3]([CH:8]([C:10]2[CH:19]=[C:18]3[C:13]([CH:14]=[CH:15][CH:16]=[N:17]3)=[CH:12][CH:11]=2)O)=[N:4][CH:5]=[CH:6][N:7]=1.[C:20]1(=[O:30])[NH:24][C:23](=[O:25])[C:22]2=[CH:26][CH:27]=[CH:28][CH:29]=[C:21]12.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[Cl:1][C:2]1[C:3]([CH:8]([C:10]2[CH:19]=[C:18]3[C:13]([CH:14]=[CH:15][CH:16]=[N:17]3)=[CH:12][CH:11]=2)[N:24]2[C:20](=[O:30])[C:21]3[C:22](=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:23]2=[O:25])=[N:4][CH:5]=[CH:6][N:7]=1

참가 물질

6

반응물 4

HCID 6809PhthalimideHCID 11776Triphenylphosphine2회HCID 5363146Diisopropyl azodicarboxylate2회HCID 57680924(3-Chloropyrazin-2-yl)-quinolin-7-ylmethanol

생성물 1

HCID 536290242-[(3-Chloropyrazin-2-yl)-quinolin-7-ylmethyl]-isoindole-1,3-dione

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

To a suspension of (3-chloropyrazin-2-yl)-quinolin-7-ylmethanol (600 mg, 2.21 mmol), phthalimide (356 mg, 2.42 mmol), and PS—PPh3 (loading 2.12 mmol/g; 1.56 g, 3.31 mmol) in dry THF (20 mL), cooled by ice/water, was added DIAD (480 L, 493 mg, 2.44 mmol), then the cooling bath was removed and the flask was vortexed at ambient temperature for 21.5 h. More PS—PPh3 (520 mg, 1.10 mmol) and DIAD (160 μL, 164 mg, 0.81 mmol) were added, and vortexing was continued for 6.5 h. The resin was filtered and washed with THF and CH2Cl2. The crude material was chromatographed on silica gel [Jones Flashmaster, 20 g/70 mL cartridge, eluting with hexanes:EtOAc 3:1 (1-14)→2:1 (15-29)→1:1 (30-65)→1:2 (66-80)], yielding the title compound as pale yellow solid; 1H NMR (CDCl3, 400 MHz) δ 7.12 (s, 1H), 7.41 (dd, J=4.4, 8.0 Hz, 1H), 7.54 (dd, J=2.0, 8.4 Hz, 1H), 7.72-7.78 (m, 2H), 7.81-7.89 (m, 3H), 8.01 (d, J=0.8 Hz, 1H), 8.16 (dd, J=0.8, 8.4 Hz, 1H), 8.39 (d, J=2.4 Hz, 1H), 8.50 (d, J=2.4 Hz, 1H), 8.90 (dd, J=1.6, 4.2 Hz, 1H); MS (ES+): m/z 401.0/402.9 (100/38) [MH+].

후처리

  1. customthe cooling bath was removed
  2. waitvortexing was continued for 6.5 h
  3. filtrationThe resin was filtered
  4. washwashed with THF and CH2Cl2
  5. customThe crude material was chromatographed on silica gel [Jones Flashmaster, 20 g/70 mL cartridge, eluting with hexanes:EtOAc 3:1 (1-14)→2:1 (15-29)→1:1 (30-65)→1:2 (66-80)]

출처 및 근거

ORD 기록
ord-5bdee25037c34680a9b5400d80832bb9
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08653268B2

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