1-Pyrrolidineethanamine → 2-(2-chloro-4-(morpholinomethyl)phenyl)-6-fluoro-N-(2-(pyrrolidin-1-yl)ethyl)quinoline-4-carboxamide

HRID 516974Notes

Reaction equation

HRID 516974 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][N:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)[CH:5]=[CH:4][C:3]=1[C:15]1[CH:24]=[C:23]([C:25]([OH:27])=O)[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([F:28])[CH:21]=2)[N:16]=1.CN1CCOCC1.ClC1N=C(OC)N=C(OC)N=1.[N:47]1([CH2:52][CH2:53][NH2:54])[CH2:51][CH2:50][CH2:49][CH2:48]1>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][N:9]2[CH2:10][CH2:11][O:12][CH2:13][CH2:14]2)[CH:5]=[CH:4][C:3]=1[C:15]1[CH:24]=[C:23]([C:25]([NH:54][CH2:53][CH2:52][N:47]2[CH2:51][CH2:50][CH2:49][CH2:48]2)=[O:27])[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([F:28])[CH:21]=2)[N:16]=1

Participants

6

Reactant 4

HCID 13441-PyrrolidineethanamineHCID 79724-MethylmorpholineHCID 184502-Chloro-4,6-dimethoxy-1,3,5-triazineHCID 898535602-(2-Chloro-4-(morpholinomethyl)phenyl)-6-fluoroquinoline-4-carboxylic acid

Product 1

HCID 717672532-(2-chloro-4-(morpholinomethyl)phenyl)-6-fluoro-N-(2-(pyrrolidin-1-yl)ethyl)quinoline-4-carboxamideYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 2-(2-chloro-4-(morpholinomethyl)phenyl)-6-fluoroquinoline-4-carboxylic acid (303 mg, 0.76 mmol) (preparation 18) in DCM (6 ml) was prepared at room temperature and N-methylmorpholine (0.166 ml, 1.51 mmol) and 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) (159 mg, 0.91 mmol) added and the mixture stirred for 1 h in a sealed vial. 2-(Pyrrolidin-1-yl)ethanamine (0.143 ml, 1.13 mmol) was then added and the mixture stirred in a sealed vial for 17 h. The mixture was then diluted with DCM (5 ml) and the organic layers washed with water (2×3 ml) and filtered through a phase separator and the organic layers concentrated under reduced pressure and purified by column chromatography (0-10% 7M NH3 in MeOH/DCM) to afford an off white solid. Analysis by 1HNMR showed impurities and the mixture was further purified by mass directed autopreparative HPLC to afford the desired product as an off-white solid (228 mg, 0.46 mmol, 61%).

Workup

  1. customwas prepared at room temperature
  2. stirringthe mixture stirred in a sealed vial for 17 h
  3. washthe organic layers washed with water (2×3 ml)
  4. filtrationfiltered through a phase separator
  5. concentrationthe organic layers concentrated under reduced pressure
  6. custompurified by column chromatography (0-10% 7M NH3 in MeOH/DCM)
  7. customto afford an off white solid
  8. customthe mixture was further purified by mass

Sources & evidence

ORD record
ord-0b1bdf4982254a1c83e8806ee7743818
Source dataset
uspto-grants-2015_08
Patent number
US09115088B2

Reaction notes

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