Cyclopentanol → HCID 89783914, compound

HRID 1055907Notes

Reaction equation

HRID 1055907 reaction equation
[CH:1]1([OH:6])[CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Cl[C:10]1[CH:19]=[CH:18][C:17]2[C:12](=[C:13]([C:20]3[NH:28][C:27]4[CH2:26][CH2:25][NH:24][C:23](=[O:29])[C:22]=4[CH:21]=3)[CH:14]=[CH:15][CH:16]=2)[N:11]=1.CCOC(C)=O>CN(C=O)C>[CH:1]1([O:6][C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[C:13]([C:20]4[NH:28][C:27]5[CH2:26][CH2:25][NH:24][C:23](=[O:29])[C:22]=5[CH:21]=4)[CH:14]=[CH:15][CH:16]=3)[N:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 7298CyclopentanolHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 897835482-(2-chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one

Product 1

HCID 89783914HCID 89783914, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Similar to the method described in Example 103, cyclopentanol (0.18 mL, 2.02 mmol) was added to a suspension of NaH (60% w/w in mineral oil) (81 mg, 2.02 mmol) in DMF (2.0 mL) and the resulting light-yellow solution was stirred at RT for 10 min. 2-(2-Chloroquinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (Example 1; 75 mg, 0.25 mmol) was then added and the resulting dark red solution was stirred at RT for 5 min, then heated at 70° C. for 3 h. The mixture was cooled to RT and partitioned between EtOAc (70 mL) and saturated aq. NH4Cl (50 mL). The organic layer was separated, sequentially washed with water (20 mL) and brine (20 mL), and then dried over MgSO4, filtered, and concentrated in vacuo. The crude residue was purified by column chromatography silica gel column, 10-100% EtOAc in hexanes over 25 min. then 100% EtOAc for 10 min.) to give 2-(2-(cyclopentyloxy)quinolin-8-yl)-6,7-dihydro-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (30 mg, 0.09 mmol, 33.8% yield) as an amorphous yellow solid: 1H NMR (400 MHz, CDCl3) δ ppm 12.70 (br. s., 1H), 7.95-8.10 (m, 2H), 7.51-7.59 (m, 1H), 7.36-7.45 (m, 1H), 7.17 (d, J=2.0 Hz, 1H), 6.90 (d, J=8.8 Hz, 1H), 5.57 (br. s., 1H), 5.44 (quin, J=4.4 Hz, 1H), 3.68 (t, J=6.7 Hz, 2H), 2.98 (t, J=6.8 Hz, 2H), 2.02-2.16 (m, 4H), 1.84-1.98 (m, 2H), 1.67-1.80 (m, 2H). m/z (ESI, +ve ion) 348.0 (M+H)+.

Workup

  1. stirringthe resulting dark red solution was stirred at RT for 5 min
  2. temperatureheated at 70° C. for 3 h
  3. temperatureThe mixture was cooled to RT
  4. custompartitioned between EtOAc (70 mL) and saturated aq. NH4Cl (50 mL)
  5. customThe organic layer was separated
  6. washsequentially washed with water (20 mL) and brine (20 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude residue was purified by column chromatography silica gel column, 10-100% EtOAc in hexanes over 25 min.

Sources & evidence

ORD record
ord-299717abf9c24e73afd43f3a5a6791d2
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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