Dimethylamine → 8-(1-(3,5-difluorophenylamino)ethyl)-N,N-dimethyl-2-((S)-3-methylmorpholino)-4-oxo-4H-chromene-6-carboxamide

HRID 572811Notes

Reaction equation

HRID 572811 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH:9][CH:10]([C:12]2[CH:13]=[C:14]([C:30]([OH:32])=O)[CH:15]=[C:16]3[C:21]=2[O:20][C:19]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][C@@H:23]2[CH3:28])=[CH:18][C:17]3=[O:29])[CH3:11])[CH:5]=[C:6]([F:8])[CH:7]=1.[CH3:33][NH:34][CH3:35].CN1CCOCC1>CN(C=O)C>[F:8][C:6]1[CH:5]=[C:4]([NH:9][CH:10]([C:12]2[CH:13]=[C:14]([C:30]([N:34]([CH3:35])[CH3:33])=[O:32])[CH:15]=[C:16]3[C:21]=2[O:20][C:19]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][C@@H:23]2[CH3:28])=[CH:18][C:17]3=[O:29])[CH3:11])[CH:3]=[C:2]([F:1])[CH:7]=1

Participants

5

Reactant 3

HCID 674DimethylamineHCID 79724-MethylmorpholineHCID 582350018-(1-(3,5-difluorophenylamino)ethyl)-2-((S)-3-methylmorpholino)-4-oxo-4H-chromene-6-carboxylic acid

Product 1

HCID 582350748-(1-(3,5-difluorophenylamino)ethyl)-N,N-dimethyl-2-((S)-3-methylmorpholino)-4-oxo-4H-chromene-6-carboxamideYield 61%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborate (55.6 mg, 0.17 mmol), was added in one portion to a stirred solution of 8-(1-(3,5-difluorophenylamino)ethyl)-2-((S)-3-methylmorpholino)-4-oxo-4H-chromene-6-carboxylic acid (70 mg, 0.16 mmol), dimethylamine (0.095 mL, 0.19 mmol) and 4-methylmorpholine (0.038 mL, 0.35 mmol) in DMF (1 mL). The resulting solution was stirred at RT for 1 hour. The reaction mixture was purified by preparative HPLC using a 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 to dryness to afford a residue which was triturated with Et2O, filtered and dried to give 8-(1-(3,5-difluorophenylamino)ethyl)-N,N-dimethyl-2-((S)-3-methylmorpholino)-4-oxo-4H-chromene-6-carboxamide (45 mg, 61%) as a pale orange solid. Mass Spectrum: M+H+ 471. NMR Spectrum (CDCl3): 1.37 (d, 1.5H), 1.41 (d, 1.5H), 1.59 (d, 1.5H), 1.60 (d, 1.5H), 2.89 (s, 1.5H), 2.91 (s, 1.5H), 3.08 (s, 3H), 3.35-3.43 (m, 1H), 3.52-3.69 (m, 2H), 3.75-3.83 (m, 2H), 3.98-4.09 (m, 2H), 4.52 (d, 1H), 4.85-4.96 (m, 1H), 5.53 (s, 1H), 5.97 (d, 2H), 6.11 (t, 1H), 7.71 (d, 0.5H), 7.73 (d, 0.5H), 8.13 (d, 1H).

Workup

  1. customThe reaction mixture was purified by preparative HPLC
  2. additionThe fractions containing the desired compound
  3. customwere evaporated to dryness
  4. customto afford a residue which
  5. customwas triturated with Et2O
  6. filtrationfiltered
  7. customdried

Sources & evidence

ORD record
ord-dfbb5493393c4f6bbf11e45b42a68024
Source dataset
uspto-grants-2015_05
Patent number
US09029374B2

Reaction notes

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