Water → HCID 178420003, compound

HRID 1772590Notes

Reaction equation

HRID 1772590 reaction equation
[NH:1]1[C:5]([C:6]2[N:11]=[CH:10][C:9]([C:12]3[N:17]4[CH:18]=[C:19]([CH2:21][OH:22])[N:20]=[C:16]4[C:15]([N:23]4[CH2:28][CH2:27][O:26][CH2:25][CH2:24]4)=[N:14][CH:13]=3)=[CH:8][CH:7]=2)=[N:4][N:3]=[N:2]1.[H-].[Na+].Cl[C:32]1[CH:41]=[CH:40][C:39]2[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=2)[N:33]=1.O>CN(C=O)C>[NH:1]1[C:5]([C:6]2[N:11]=[CH:10][C:9]([C:12]3[N:17]4[CH:18]=[C:19]([CH2:21][O:22][C:32]5[CH:41]=[CH:40][C:39]6[C:34](=[CH:35][CH:36]=[CH:37][CH:38]=6)[N:33]=5)[N:20]=[C:16]4[C:15]([N:23]4[CH2:28][CH2:27][O:26][CH2:25][CH2:24]4)=[N:14][CH:13]=3)=[CH:8][CH:7]=2)=[N:4][N:3]=[N:2]1

Participants

6

Reactant 4

HCID 962WaterHCID 119282-ChloroquinolineHCID 24758Sodium hydrideHCID 178519789HCID 178519789, compound

Product 1

HCID 178420003HCID 178420003, compoundYield 11%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of compound 1h (187 mg, 0.510 mmol) in DMF (2 mL) was added sodium hydride (49.0 mg, 2.04 mmol) in portions at 0° C. The mixture was stirred for 15 min before the addition of 2-chloroquinoline (125 mg, 0.765 mmol). The reaction mixture was stirred at 70° C. overnight. Water was added, and the resulting mixture was extracted with DCM (3×10 mL). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel with EtOAc/petroleum ether (1:3 v/v) to obtain the title compound 97 as a yellow solid (27.6 mg, 11% yield). 1H-NMR (300 MHz, DMSO-d6) δ (ppm): 8.23-8.28 (m, 1H), 8.25 (d, J=8.7 Hz, 1H), 8.23-8.15 (m, 1H), 7.89 (d, J=8.1 Hz, 1H), 7.80 (d, J=8.4 Hz, 1H), 7.68 (t, J=7.2 Hz, 1H), 7.63-7.55 (m, 1H), 7.44 (t, J=7.2 Hz, 1H), 7.06 (d, J=8.7 Hz, 1H), 7.03-7.00 (m, 1H), 5.59 (s, 2H), 4.35-4.20 (m, 4H), 3.85-3.69 (m, 4H). Mass Spectrum (LCMS, ESI pos.): Calcd. for C26H22N10O2: 507.2 (M+H). Found 507.2.

Workup

  1. extractionthe resulting mixture was extracted with DCM (3×10 mL)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. customThe resulting residue was purified by flash column chromatography on silica gel with EtOAc/petroleum ether (1:3 v/v)

Sources & evidence

ORD record
ord-d72bc60b544e4bd8b080ff9124dcf333
Source dataset
uspto-grants-2016_02
Patent number
US09249163B2

Reaction notes

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