4-Methylmorpholine → 8-(1-((3,5-difluorophenyl)(methyl)amino)ethyl)-6-(4-hydroxypiperidine-1-carbonyl)-2-morpholino-4H-chromen-4-one

HRID 1947344Notes

Reaction equation

HRID 1947344 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:9]([CH3:32])[CH:10]([C:12]2[CH:13]=[C:14]([C:29](O)=[O:30])[CH:15]=[C:16]3[C:21]=2[O:20][C:19]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[CH:18][C:17]3=[O:28])[CH3:11])[CH:5]=[C:6]([F:8])[CH:7]=1.CN1CCOCC1.[NH:40]1[CH2:45][CH2:44][CH:43]([OH:46])[CH2:42][CH2:41]1>CN1C(=O)CCC1>[F:1][C:2]1[CH:3]=[C:4]([N:9]([CH3:32])[CH:10]([C:12]2[CH:13]=[C:14]([C:29]([N:40]3[CH2:45][CH2:44][CH:43]([OH:46])[CH2:42][CH2:41]3)=[O:30])[CH:15]=[C:16]3[C:21]=2[O:20][C:19]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[CH:18][C:17]3=[O:28])[CH3:11])[CH:5]=[C:6]([F:8])[CH:7]=1

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 79341Piperidin-4-olHCID 582349758-(1-((3,5-difluorophenyl)(methyl)amino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid

Product 1

HCID 582349708-(1-((3,5-difluorophenyl)(methyl)amino)ethyl)-6-(4-hydroxypiperidine-1-carbonyl)-2-morpholino-4H-chromen-4-oneYield 58.8%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
23 °C

Procedure

2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborate (113 mg, 0.35 mmol) was added to a stirred solution of 8-(1-((3,5-difluorophenyl)(methyl)amino)ethyl)-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid (130 mg, 0.29 mmol), 4-methylmorpholine (0.080 mL, 0.73 mmol) and piperidin-4-ol (36 mg, 0.35 mmol) dissolved in NMP (1.2 mL). The resulting solution was stirred at 23° C. for 2 hrs. The reaction mixture was purified by preparative HPLC using a Waters SunFire system. The fractions containing the desired compound were evaporated, triturated with ether and dried to afford 8-(1-((3,5-difluorophenyl)(methyl)amino)ethyl)-6-(4-hydroxypiperidine-1-carbonyl)-2-morpholino-4H-chromen-4-one (90 mg, 58%) as a white solid. Mass Spectrum: M+H+ 528. NMR Spectrum (DMSOd6 at 323° K): 1.38 (bs, 2H), 1.57 (d, 3H), 1.75 (bs, 2H), 2.66 (s, 3H), 3.23-3.30 (m, 2H), 3.30-3.38 (m, 2H), 3.61 (m, 4H), 3.65 (bs, 4H), 3.71-3.79 (m, 1H), 4.66 (d, 1H), 5.52 (s, 1H), 5.54 (q, 1H), 6.36 (t, 1H), 6.50 (d, 2H), 7.62 (d, 1H), 7.87 (d, 1H).

Workup

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

Sources & evidence

ORD record
ord-ea4cfb7a8fcb4c43a5faeb7cb3a8fb98
Source dataset
uspto-grants-2013_03
Patent number
US08399460B2

Reaction notes

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