2-Ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinoline → HCID 66813090, compound
Reaction equation
[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([F:9])[CH:3]=1.[C:10]1([CH2:16][C:17]([N:19]2[CH2:26][CH2:25][CH2:24][C@H:20]2[C:21](O)=[O:22])=[O:18])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CCOC1N(C(OCC)=O)C2C(=CC=CC=2)C=C1>>[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][C:21](=[O:22])[C@@H:20]2[CH2:24][CH2:25][CH2:26][N:19]2[C:17](=[O:18])[CH2:16][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[C:4]([F:9])[CH:3]=1Participants
Procedure
4-Bromo-2-fluoroaniline (1.0 g, 5.3 mmol) was treated with N-phenylacetylproline (1.3 g, 5.52 mmol) and EEDQ as described in Example 1 to provide 2.1 g of N-(4-bromo-2-fluorophenyl)-1-(phenylacetyl)-L-prolinamide. A portion of this intermediate (0.51 g, 1.26 mmol) was suspended in 5 mL toluene and treated with 0.38 mL of trans-1,2-bis(tri-n-butylstannyl)ethylene (0.69 mmol, 0.55 equiv) followed by 0.029 g of Pd(PPh3)4. The reaction was sealed under nitrogen and heated to 100° C. for 2 hours. The mixture was then cooled to room temperature and stirred vigorously with an equal volume of aqueous saturated KF for 2 hours. Filtration through diatomaceous earth (Celite®) followed by extractive workup and HPLC purification provided the desired product. 1H NMR (DMSO-d6, 500 MHz, mixture of rotamers) δ 10.10 and 9.86 (s, 1H), 7.94 and 7.81 (m, 1H), 7.52 (m, 1H), 7.20-7.35 (m, 16H), 4.82 and 4.64 (m, 2H), 3.65 (m, 4H), 1.94-2.11 (m, 8H); LCMS (Rt=1.76 min, m/z 677.34).
Sources & evidence
- ORD record
- ord-f4f42e0405dc4243956d7e7e403fca9c
- Source dataset
- uspto-grants-2012_03
- Patent number
- US08143288B2
Reaction notes
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