Water → HCID 56847342, compound

HRID 1467383Notes

Reaction equation

HRID 1467383 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[N:10]1[C:22]2[C:21]3[CH:20]=[C:19]([OH:23])[C:18]([O:24][CH3:25])=[CH:17][C:16]=3[N:15]=[CH:14][C:13]=2[N:12]([CH3:26])[C:11]1=[O:27])[C:5]#[N:6].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:35][C:36]1[CH:40]=[CH:39][S:38][CH:37]=1.O>CN(C)C=O>[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[N:10]1[C:22]2[C:21]3[CH:20]=[C:19]([O:23][CH2:35][C:36]4[CH:40]=[CH:39][S:38][CH:37]=4)[C:18]([O:24][CH3:25])=[CH:17][C:16]=3[N:15]=[CH:14][C:13]=2[N:12]([CH3:26])[C:11]1=[O:27])[C:5]#[N:6]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 124874623-(Chloromethyl)thiopheneHCID 66611737HCID 66611737, compound

Product 1

HCID 56847342HCID 56847342, compoundYield 63.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

3-Fluoro-4-(8-hydroxy-7-methoxy-3-methyl-2-oxo-2,3-dihydroimidazo[4,5-c]quinolin-1-yl)benzonitrile (80 mg, 220 μmol) was dissolved in N,N-dimethylformamide (4.0 ml) under a dry argon atmosphere. Potassium carbonate (85 mg, 618 μmol) and 3-chloromethylthiophene (112 mg, 845 μmol; prepared from 3-thiophenemethanol using SOCl2 in CH2Cl2) were subsequently added. The reaction mixture was stirred at 50° C. for 18 h overnight. When the reaction was complete, the mixture was poured into water (60 ml), stirred for 30 min and extracted twice with ethyl acetate (75 ml each time). The combined organic phases were washed with water (25 ml), subsequently dried over Na2SO4, filtered with suction and evaporated in vacuo. The residue chromatographed over flash silica gel (solvent gradient ethyl acetate/0-17% by vol. of ethanol), giving 3-fluoro-4-(7-methoxy-3-methyl-2-oxo-8-(thiophen-3-ylmethoxy)-2,3-dihydroimidazo[4,5-c]quinolin-1-yl)benzonitrile (64 mg, 139 μmol), as solid. MS: 461.1 (M+H+), TLC (HPTLC): Rf=0.33 (ethyl acetate/ethanol 5:1, parts by volume).

Workup

  1. stirringstirred for 30 min
  2. extractionextracted twice with ethyl acetate (75 ml each time)
  3. washThe combined organic phases were washed with water (25 ml)
  4. dry with materialsubsequently dried over Na2SO4
  5. filtrationfiltered with suction
  6. customevaporated in vacuo
  7. customThe residue chromatographed over flash silica gel (solvent gradient ethyl acetate/0-17% by vol. of ethanol)

Sources & evidence

ORD record
ord-eb8b8910ac4f43e5983055ea8cc8cc16
Source dataset
uspto-grants-2015_04
Patent number
US09000153B2

Reaction notes

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