8-Hydroxyquinoline → HCID 70805297, compound

HRID 475014Notes

Reaction equation

HRID 475014 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[CH2:16][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:14][CH2:13][CH2:12][C:7]=3[N:8]([CH3:11])[C:9]=2[CH:10]=1.[F:24][C:25]([F:40])([F:39])[C:26]1[N:31]=[CH:30][C:29]([C:32]2[CH:37]=[CH:36][NH:35][C:34](=[O:38])[N:33]=2)=[CH:28][CH:27]=1.OC1C=CC=C2C=1N=CC=C2.C([O-])([O-])=O.[Cs+].[Cs+].C(N(CC)CC)C>CS(C)=O.CCOC(C)=O.[Cu]I>[CH3:11][N:8]1[C:9]2[CH:10]=[C:2]([N:35]3[CH:36]=[CH:37][C:32]([C:29]4[CH:30]=[N:31][C:26]([C:25]([F:24])([F:39])[F:40])=[CH:27][CH:28]=4)=[N:33][C:34]3=[O:38])[CH:3]=[CH:4][C:5]=2[C:6]2[CH2:16][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:14][CH2:13][CH2:12][C:7]1=2

Participants

9

Reactant 5

HCID 19238-HydroxyquinolineHCID 8471TriethylamineHCID 10796Cesium carbonateHCID 66874851tert-Butyl 8-bromo-6-methyl-3,4,5,6-tetrahydroazepino[4,3-b]indole-2(1H)-carboxylateHCID 178517475HCID 178517475, compound

Product 1

HCID 70805297HCID 70805297, compoundYield 72%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
135 °C

Procedure

A suspension of tert-butyl 8-bromo-6-methyl-3,4,5,6-tetrahydroazepino[4,3-b]indole-2(1H)-carboxylate (105 mg, 0.28 mmol), 4-(6-(trifluoromethyl)pyridin-3-yl)pyrimidin-2(1H)-one (50 mg, 0.18 mmol), 8-hydroxyquinoline (6 mg, 0.04 mmol) and Cs2CO3 (0.12 g, 0.37 mmol) in DMSO (5.0 mL) was degassed under reduced pressure for 30 min. CuI (61.9 mg, 0.33 mmol) was added to the above solution, and the reaction mixture was degassed under reduced pressure for 5 min. Triethylamine (0.025 mL, 0.18 mmol) was added to the above solution. The resulting suspension was stirred at 135° C. for 20 h. The reaction mixture was cooled and diluted with EtOAc. The resulting solution was washed sequentially with aqueous ammonium chloride and aqueous LiCl (5%), dried over sodium sulfate and concentrated under reduced pressure. The resulting crude material was dissolved in DCM, treated with charcoal and purified by preparative TLC (DCM/MeOH 95:5) to afford the title compound (55.0 mg, 72%) as a brown yellow solid and as a mixture of rotamers: 1H NMR (500 MHz, CDCl3) δ 9.35 (d, J=1.5 Hz, 1H), 8.75 (d, J=8.0 Hz, 1H), 8.02-7.99 (m, 1H), 7.86 (d, J=8.5 Hz, 1H), 7.69 (d, J=8.5 Hz, 0.3H), 7.59 (d, J=8.5 Hz, 0.7H), 7.40 (s, 1H), 7.09-7.06 (m, 1H), 6.93 (d, J=7.0 Hz, 1H), 4.72 (s, 0.7H), 4.64 (s, 1.3H), 3.79-3.67 (m, 2H), 3.69 (s, 3H), 2.99-2.97 (m, 2H), 2.08-2.02 (m, 2H), 1.44 (s, 3.3H), 1.38 (s, 5.7H).

Workup

  1. customwas degassed under reduced pressure for 30 min
  2. customthe reaction mixture was degassed under reduced pressure for 5 min
  3. temperatureThe reaction mixture was cooled
  4. washThe resulting solution was washed sequentially with aqueous ammonium chloride and aqueous LiCl (5%)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe resulting crude material was dissolved in DCM
  8. additiontreated with charcoal
  9. custompurified by preparative TLC (DCM/MeOH 95:5)

Sources & evidence

ORD record
ord-17b812c5de2c421fb9b483d4cd9f9cce
Source dataset
uspto-grants-2014_01
Patent number
US08637501B2

Reaction notes

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