1-Pyrrolidineethanamine → HCID 86732741, compound

HRID 525874Notes

Reaction equation

HRID 525874 reaction equation
[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=3)=[C:10]([O:13][CH2:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=3)[CH:11]=2)[C:6](=[O:33])[C:5]([C:34]([OH:36])=O)=[N:4]1)[CH3:2].S(Cl)(Cl)=O.[N:41]1([CH2:46][CH2:47][NH2:48])[CH2:45][CH2:44][CH2:43][CH2:42]1.C(N(CC)CC)C>ClCCl>[CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][C:9]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=3)=[C:10]([O:13][CH2:14][C:15]3[CH:16]=[CH:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=3)[CH:11]=2)[C:6](=[O:33])[C:5]([C:34]([NH:48][CH2:47][CH2:46][N:41]2[CH2:45][CH2:44][CH2:43][CH2:42]2)=[O:36])=[N:4]1)[CH3:2]

Participants

6

Reactant 4

HCID 13441-PyrrolidineethanamineHCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 86732737HCID 86732737, compound

Product 1

HCID 86732741HCID 86732741, compoundYield 73.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of 1-ethyl-6,7-bis((4-methoxybenzyl)oxy)-4-oxo-1,4-dihydrocinnoline-3-carboxylic acid (Example 8c) (2.5 g, 5.10 mmol) in dichloromethane (50 mL) at room temperature was added thionyl chloride (0.446 mL, 6.12 mmol), and the mixture was heated to reflux for 1 h. After cooling to room temperature the mixture was added dropwise to a solution of 2-(pyrrolidin-1-yl)ethanamine (0.711 mL, 5.61 mmol) and triethylamine (1.066 mL, 7.65 mmol) in dichloromethane (50.0 mL) in an ice bath. The resulting mixture was then allowed to warm up to room temperature, and stirred for another 0.5 h. LCMS indicated completion of the reaction. The mixture was concentrated in vacuo, and the residue was purified twice by automatic silica gel column chromatography (Combiflash RF), eluting with a mixture of [dichloromethane/methanol/ammonium hydroxide (80:20:2)]/dichloromethane (0-50%) to afford 1-ethyl-6,7-bis((4-methoxybenzyl)oxy)-4-oxo-N-(2-(pyrrolidin-1-yl)ethyl)-1,4-dihydrocinnoline-3-carboxamide (2.2 g, 3.75 mmol, 73.6% yield) as a light yellow solid. LCMS: (M+H)+: 587.3.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 1 h
  3. temperatureto warm up to room temperature
  4. customcompletion of the reaction
  5. concentrationThe mixture was concentrated in vacuo
  6. customthe residue was purified twice by automatic silica gel column chromatography (Combiflash RF)
  7. washeluting with a mixture of [dichloromethane/methanol/ammonium hydroxide (80:20:2)]/dichloromethane (0-50%)

Sources & evidence

ORD record
ord-c9b75b5e1dbc47cd9a2b800227a072a6
Source dataset
uspto-grants-2016_05
Patent number
US09340556B2

Reaction notes

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