Dimethylamine → 9-(3-Chloro-4-fluoroanilino)-1-[4-(dimethylamino)butyl]-2,3-dihydro-1H-[1,4]oxazino[3,2-g]quinoline-8-carbonitrile

HRID 396184Notes

Reaction equation

HRID 396184 reaction equation
Cl[CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:11]2=[CH:12][C:13]3[C:14]([NH:22][C:23]4[CH:28]=[CH:27][C:26]([F:29])=[C:25]([Cl:30])[CH:24]=4)=[C:15]([C:20]#[N:21])[CH:16]=[N:17][C:18]=3[CH:19]=[C:10]2[O:9][CH2:8][CH2:7]1.[I-].[Na+].[CH3:33][NH:34][CH3:35].O1CCCC1.C(=O)(O)[O-].[Na+]>CN(C)C=O.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C>[Cl:30][C:25]1[CH:24]=[C:23]([CH:28]=[CH:27][C:26]=1[F:29])[NH:22][C:14]1[C:13]2[CH:12]=[C:11]3[N:6]([CH2:5][CH2:4][CH2:3][CH2:2][N:34]([CH3:35])[CH3:33])[CH2:7][CH2:8][O:9][C:10]3=[CH:19][C:18]=2[N:17]=[CH:16][C:15]=1[C:20]#[N:21]

Participants

9

Reactant 5

HCID 674DimethylamineHCID 5238Sodium IodideHCID 8028TetrahydrofuranHCID 516892Sodium BicarbonateHCID 102255121-(4-chlorobutyl)-9-(3-chloro-4-fluoroanilino)-2,3-dihydro-1H-[1,4]oxazino[3,2-g]quinoline-8-carbonitrile

Product 1

HCID 101826229-(3-Chloro-4-fluoroanilino)-1-[4-(dimethylamino)butyl]-2,3-dihydro-1H-[1,4]oxazino[3,2-g]quinoline-8-carbonitrileYield 58%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

An amount of 1-(4-chlorobutyl)-9-(3-chloro-4-fluoroanilino)-2,3-dihydro-1H-[1,4]oxazino[3,2-g]quinoline-8-carbonitrile (150 mg, 0.34 mmol) was stirred in N,N-dimethylformamide (1.5 ml), and to this were added sodium iodide (76 mg, 0.51 mmol), tetrabutyl ammonium iodide (25.9 mg, 0.07 mmol), and dimethylamine in tetrahydrofuran (2M) (5.4 mL, 10.8 mmol). The mixture was heated at 45° C. for 4 hours, cooled to room temperature, and stirred with ethyl acetate and saturated sodium bicarbonate solution. After separation of the layers, the organic layer was dried over sodium sulfate and evaporated to an oil. Purification was performed by preparative thin layer chromatography (60% acetone in methanol) to give a yellow solid (89 mg, 58% yield), m.p. 105° C.; 1H NMR (DMSO-d6) δ 9.50-9.00 (bs, 1H), 8.20 (s, 1H), 7.33 (t, 1H), 7.26 (dd, 1H), 7.23 (s, 1H), 7.07 (m, 2H), 4.30 t, 2H), 3.37 (m, 4H), 2.18 (t, 2H), 2.06 (s, 6H), 1.55 (m, 2H), 1.40 (m, 2H); HRMS (EI) m/z 453.1736 (M+1).

Workup

  1. temperaturecooled to room temperature
  2. customAfter separation of the layers
  3. dry with materialthe organic layer was dried over sodium sulfate
  4. customevaporated to an oil
  5. customPurification

Sources & evidence

ORD record
ord-1f15add2935f490b9c439aef4909601b
Source dataset
uspto-grants-2003_08
Patent number
US06608048B2

Reaction notes

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