2-(Methylamino)ethanol → 8-(1-((3,5-difluorophenyl)(methyl)amino)ethyl)-N-(2-hydroxyethyl)-N-methyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide

HRID 572788Notes

Reaction equation

HRID 572788 reaction equation
CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[F:23][C:24]1[CH:25]=[C:26]([N:31]([CH3:54])[CH:32]([C:34]2[CH:35]=[C:36]([C:51](O)=[O:52])[CH:37]=[C:38]3[C:43]=2[O:42][C:41]([N:44]2[CH2:49][CH2:48][O:47][CH2:46][CH2:45]2)=[CH:40][C:39]3=[O:50])[CH3:33])[CH:27]=[C:28]([F:30])[CH:29]=1.C(N(C(C)C)C(C)C)C.[CH3:64][NH:65][CH2:66][CH2:67][OH:68]>CN(C=O)C>[F:30][C:28]1[CH:27]=[C:26]([N:31]([CH3:54])[CH:32]([C:34]2[CH:35]=[C:36]([C:51]([N:65]([CH2:66][CH2:67][OH:68])[CH3:64])=[O:52])[CH:37]=[C:38]3[C:43]=2[O:42][C:41]([N:44]2[CH2:45][CH2:46][O:47][CH2:48][CH2:49]2)=[CH:40][C:39]3=[O:50])[CH3:33])[CH:25]=[C:24]([F:23])[CH:29]=1

Participants

6

Reactant 4

HCID 80162-(Methylamino)ethanolHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 582349758-(1-((3,5-difluorophenyl)(methyl)amino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid

Product 1

HCID 582350098-(1-((3,5-difluorophenyl)(methyl)amino)ethyl)-N-(2-hydroxyethyl)-N-methyl-2-morpholino-4-oxo-4H-chromene-6-carboxamideYield 64.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

TBTU (108 mg, 0.34 mmol) was added in one portion to a stirred solution of 8-(1-((3,5-difluorophenyl)(methyl)amino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid (125 mg, 0.28 mmol), N-ethyl-N-isopropylpropan-2-amine (0.103 mL, 0.59 mmol) and 2-(methylamino)ethanol (0.027 mL, 0.34 mmol) in DMF (1 mL). The resulting solution was stirred at RT for 2 hrs. The reaction mixture was filtered and 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 8-(1-((3,5-difluorophenyl)(methyl)amino)ethyl)-N-(2-hydroxyethyl)-N-methyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (90 mg, 64%) as a off-white solid. Mass Spectrum: M+H+ 502. NMR Spectrum (DMSOd6 at 323° K): 1.58 (d, 3H), 2.65 (s, 3H), 3.01 (s, 3H), 3.23-3.40 (m, 5H), 3.4-3.71 (m, 7H), 4.74 (bs, 1H), 5.52 (s, 1H), 5.57 (q, 1H), 6.38 (t, 1H), 6.53 (d, 2H), 7.74 (bs, 1H), 7.93 (s, 1H).

Workup

  1. filtrationThe reaction mixture was filtered
  2. custompurified by preparative HPLC
  3. additionThe fractions containing the desired compound
  4. customwere evaporated to dryness

Sources & evidence

ORD record
ord-5ab0f04c14c84943b62dcb88b09c5c34
Source dataset
uspto-grants-2015_05
Patent number
US09029374B2

Reaction notes

Loading…