2-Amino-6-fluorobenzonitrile → 8-(1-(2-cyano-3-fluorophenylamino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide

HRID 572775Notes

Reaction equation

HRID 572775 reaction equation
[NH2:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[C:3]=1[C:4]#[N:5].Br.Br[CH:13]([C:15]1[CH:16]=[C:17]([C:32]([N:34]([CH3:36])[CH3:35])=[O:33])[CH:18]=[C:19]2[C:24]=1[O:23][C:22]([N:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1)=[CH:21][C:20]2=[O:31])[CH3:14]>>[C:4]([C:3]1[C:6]([F:10])=[CH:7][CH:8]=[CH:9][C:2]=1[NH:1][CH:13]([C:15]1[CH:16]=[C:17]([C:32]([N:34]([CH3:36])[CH3:35])=[O:33])[CH:18]=[C:19]2[C:24]=1[O:23][C:22]([N:25]1[CH2:30][CH2:29][O:28][CH2:27][CH2:26]1)=[CH:21][C:20]2=[O:31])[CH3:14])#[N:5]

Participants

3

Reactant 2

HCID 5226592-Amino-6-fluorobenzonitrileHCID 671036758-(1-bromoethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide hydrobromide

Product 1

HCID 582349888-(1-(2-cyano-3-fluorophenylamino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamideYield 64.3%

Procedure

2-amino-6-fluorobenzonitrile (111 mg, 0.82 mmol) was reacted with 8-(1-bromoethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide hydrobromide (100 mg, 0.20 mmol) using an analogous procedure to the one described in Example 3.03. The crude product was purified by flash chromatography on silica gel eluting with 0 to 10% MeOH in DCM. The solvent was evaporated to dryness. The resulting oil was crystallised from ethyl acetate to give 8-(1-(2-cyano-3-fluorophenylamino)ethyl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (45.0 mg, 64.3%) as a white solid. Mass Spectrum: M+H+ 465. NMR Spectrum (DMSOd6): 1.61 (d, 3H), 2.74 (bs, 3H), 2.95 (bs, 3H), 3.49-3.62 (m, 4H), 3.69-3.77 (m, 4H), 5.17-5.26 (m, 1H), 5.61 (s, 1H), 6.33 (d, 1H), 6.56 (dd, 1H), 6.99 (d, 1H), 7.32 (dd, 1H), 7.69 (d, 1H), 7.81 (d, 1H).

Workup

  1. customThe crude product was purified by flash chromatography on silica gel eluting with 0 to 10% MeOH in DCM
  2. customThe solvent was evaporated to dryness
  3. customThe resulting oil was crystallised from ethyl acetate

Sources & evidence

ORD record
ord-6c6c85e9098b442db8f0cacd8cc3e8f4
Source dataset
uspto-grants-2015_05
Patent number
US09029374B2

Reaction notes

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