4-Methylmorpholine → 8-(1-(3-chloro-2-fluorophenylamino)ethyl)-N-(2-(dimethylamino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxamide

HRID 1947287Notes

Reaction equation

HRID 1947287 reaction equation
[Cl:1][C:2]1[C:3]([F:31])=[C:4]([NH:8][CH:9]([C:11]2[CH:12]=[C:13]([C:28](O)=[O:29])[CH:14]=[C:15]3[C:20]=2[O:19][C:18]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[CH:17][C:16]3=[O:27])[CH3:10])[CH:5]=[CH:6][CH:7]=1.[CH3:32][N:33]1[CH2:38]CO[CH2:35][CH2:34]1.C[N:40]1C(=O)CCC1>>[Cl:1][C:2]1[C:3]([F:31])=[C:4]([NH:8][CH:9]([C:11]2[CH:12]=[C:13]([C:28]([NH:40][CH2:35][CH2:34][N:33]([CH3:38])[CH3:32])=[O:29])[CH:14]=[C:15]3[C:20]=2[O:19][C:18]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[CH:17][C:16]3=[O:27])[CH3:10])[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 3

HCID 79724-MethylmorpholineHCID 13387N-methyl-2-pyrrolidoneHCID 582350028-(1-(3-chloro-2-fluorophenylamino) ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid

Product 1

HCID 529135908-(1-(3-chloro-2-fluorophenylamino)ethyl)-N-(2-(dimethylamino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxamideYield 60.2%

Procedure

2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborate (73.3 mg, 0.23 mmol) was added to a stirred solution of 8-(1-(3-chloro-2-fluorophenylamino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid (85 mg, 0.19 mmol), 4-methylmorpholine (0.052 mL, 0.48 mmol) and N1,N1-dimethylethane-1,2-m diamine (0.025 mL, 0.23 mmol) dissolved in NMP (1.2 mL) at room temperature. The resulting solution was stirred for 2 hrs. The reaction mixture was purified by preparative HPLC using a Waters SunFire reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 mL/minute) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions containing the desired compound were evaporated, triturated with diethyl ether and dried to afford 8-(1-(3-chloro-2-fluorophenylamino)ethyl)-N-(2-(dimethylamino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxamide (59.2 mg, 60.2%) as a white solid. Mass Spectrum: M+H+ 517. NMR Spectrum: (DMSOd6) 1.57 (d, 3H), 2.15 (s, 6H), 2.37 (t, 2H), 3.26-3.34 (m partially hidden by H2O, 2H), 3.50-3.62 (m, 4H), 3.70-3.79 (m, 4H), 5.03-5.12 (m, 1H), 5.61 (s, 1H), 6.34 (dd, 1H), 6.49 (d, 1H), 6.64 (ddd, 1H), 6.82 (d, 1H), 8.10 (d, 1H), 8.32 (d, 1H), 8.61 (t, 1H).

Workup

  1. customThe reaction mixture was purified by preparative HPLC
  2. additionThe fractions containing the desired compound
  3. customwere evaporated
  4. customtriturated with diethyl ether
  5. customdried

Sources & evidence

ORD record
ord-da77dcc65b174e7ca8b671d2fb834ae2
Source dataset
uspto-grants-2013_03
Patent number
US08399460B2

Reaction notes

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