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

HRID 422618ノート

反応式

HRID 422618 の反応式
[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

参加物

6

反応物 4

HCID 6809PhthalimideHCID 11776Triphenylphosphine2 回HCID 5363146Diisopropyl azodicarboxylate2 回HCID 57680924(3-Chloropyrazin-2-yl)-quinolin-7-ylmethanol

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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 μL, 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+].

後処理

  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)]

出典と根拠

ORDレコード
ord-b924076dd7df46ddad94168ecf34f4ed
出典データセット
uspto-grants-2012_01
特許番号
US08101613B2

反応ノート

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