2-Chloroquinoline → HCID 117732310, compound

HRID 1772740Notes

Reaction equation

HRID 1772740 reaction equation
[OH:1][CH2:2][C:3]1[N:4]=[C:5]2[C:10]([C:11]3[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=3)=[N:9][CH:8]=[C:7]([C:17]3[CH:18]=[CH:19][C:20]([N:23]4[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]4)=[N:21][CH:22]=3)[N:6]2[CH:36]=1.Cl[C:38]1[CH:47]=[CH:46][C:45]2[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=2)[N:39]=1.C1OCCOCCOCCOCCOCCOC1.CC(C)([O-])C.[K+]>C1COCC1.CCOC(C)=O>[N:14]1[CH:13]=[CH:12][C:11]([C:10]2[C:5]3[N:6]([CH:36]=[C:3]([CH2:2][O:1][C:38]4[CH:47]=[CH:46][C:45]5[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=5)[N:39]=4)[N:4]=3)[C:7]([C:17]3[CH:18]=[CH:19][C:20]([N:23]4[CH2:24][CH2:25][N:26]([C:29]([O:31][C:32]([CH3:33])([CH3:35])[CH3:34])=[O:30])[CH2:27][CH2:28]4)=[N:21][CH:22]=3)=[CH:8][N:9]=2)=[CH:16][CH:15]=1

Participants

7

Reactant 4

HCID 119282-ChloroquinolineHCID 2855718-Crown-6HCID 23665647Potassium tert-butoxideHCID 117733756HCID 117733756, compound

Product 1

HCID 117732310HCID 117732310, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of compound 87d (80.0 mg, 0.164 mmol), 2-chloroquinoline (40.3 mg, 0.246 mmol) and 18-crown-6 (43.8 mg, 0.164 mmol) in 5 mL of THF at rt was added potassium tert-butoxide (0.328 mL, 0.328 mmol, 1.0M in t-BuOH). The resulting mixture was heated to 60° C. and continued to stir for 0.5 h. After cooling to rt, the mixture was treated with 30 mL of EtOAc and washed with water (2×10 mL) and brine (10 mL). Removal of the solvent under reduced pressure followed by purification of the resultant residue by flash column chromatography on silica gel (0-4% MeOH/DCM) gave compound 87e as a yellow solid. 1H-NMR (CDCl3; 400 MHz) δ 8.82 (br. s., 2H), 8.70 (br. s., 2H), 8.51 (br. s., 1H), 7.91-8.09 (m, 3H), 7.70-7.91 (m, 3H), 7.64 (t, J=7.2 Hz, 1H), 7.41 (t, J=6.8 Hz, 1H), 6.99 (d, J=8.6 Hz, 1H), 6.79 (d, J=8.6 Hz, 1H), 5.84 (s, 2H), 3.70 (br. s., 4H), 3.60 (br. s., 4H), 1.51 (s, 9H). Mass spectrum (LCMS, ESI pos.): Calcd. for C35H34N8O3, 615.3 (M+H). found 615.2.

Workup

  1. temperatureAfter cooling to rt
  2. washwashed with water (2×10 mL) and brine (10 mL)
  3. customRemoval of the solvent under reduced pressure
  4. customfollowed by purification of the resultant residue by flash column chromatography on silica gel (0-4% MeOH/DCM)

Sources & evidence

ORD record
ord-f8cfb915df704a08ab97e08f5839fda7
Source dataset
uspto-grants-2016_02
Patent number
US09249163B2

Reaction notes

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