Dimethylformamide → {4-Chloro-2-[methoxy(methyl)amino]-3-phenylquinolin-6-yl}(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol

HRID 1478525Notes

Reaction equation

HRID 1478525 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:16]2[CH:17]=[C:18]3[C:23](=[CH:24][CH:25]=2)[N:22]=[C:21](Cl)[C:20]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[C:19]3[Cl:33])([C:10]2[N:14]([CH3:15])[CH:13]=[N:12][CH:11]=2)[OH:9])=[CH:4][CH:3]=1.Cl.[CH3:35][NH:36][O:37][CH3:38].CN(C)C=O>CCOC(C)=O>[Cl:33][C:19]1[C:18]2[C:23](=[CH:24][CH:25]=[C:16]([C:8]([C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)([C:10]3[N:14]([CH3:15])[CH:13]=[N:12][CH:11]=3)[OH:9])[CH:17]=2)[N:22]=[C:21]([N:36]([O:37][CH3:38])[CH3:35])[C:20]=1[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 90100965(4-Chlorophenyl)(2,4-dichloro-3-phenylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanol

Product 1

HCID 118005588{4-Chloro-2-[methoxy(methyl)amino]-3-phenylquinolin-6-yl}(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanol

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

(4-Chlorophenyl)(2,4-dichloro-3-phenylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanol (250 mg, 0.505 mmol, Example 65), N,O-dimethylhydroxylamine hydrochloride (1.01 g, 10.1 mmol), and dimethylformamide (2 mL) were combined in a reaction tube, which was then sealed and heated to 100° C. for 48 hours. The contents were then cooled, transferred to a reparatory funnel, diluted with EtOAc and extracted with saturated, aqueous NH4Cl solution, followed by deionized water (4×). The organic phase was separated and dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified via reverse phase chromatography using acetonitrile with ammonium hydroxide in water as eluent to afford the title compound. MS (ESI): mass calcd. for C28H24Cl2N4O2, 518.1; m/z found, 519.2 [M+H]+; 1H NMR (400 MHz, CD3OD) δ ppm 8.14 (d, J=1.9 Hz, 1H), 7.91 (d, J=8.8 Hz, 1H), 7.70 (dd, J=8.8, 2.1 Hz, 1H), 7.67 (s, 1H), 7.47 (dd, J=11.4, 4.3 Hz, 2H), 7.39 (dt, J=4.4, 1.8 Hz, 1H), 7.36 (d, J=4.1 Hz, 4H), 7.26 (dd, J=8.2, 1.3 Hz, 2H), 6.28 (s, 1H), 3.46 (s, 3H), 3.05 (s, 3H), 2.76 (s, 3H).

Workup

  1. customwhich was then sealed
  2. temperatureThe contents were then cooled
  3. customtransferred to a reparatory funnel
  4. extractionextracted with saturated, aqueous NH4Cl solution
  5. customThe organic phase was separated
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude material was purified via reverse phase chromatography

Sources & evidence

ORD record
ord-1cc8f9f3cb65483abc60b5075b7f5eb8
Source dataset
uspto-grants-2016_08
Patent number
US09403816B2

Reaction notes

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