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

HRID 1163130Notes

Reaction equation

HRID 1163130 reaction equation
[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

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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+].

Workup

  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)]

Sources & evidence

ORD record
ord-b0238167985e4f40bd61138e0cb058b0
Source dataset
uspto-grants-2010_10
Patent number
US07820662B2

Reaction notes

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