Morpholine → 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-6-(morpholine-4-carbonyl)-2-morpholino-4H-chromen-4-one

HRID 41182Notes

Reaction equation

HRID 41182 reaction equation
Cl.C(N=C=NCCCN(C)C)C.[F:13][C:14]1[CH:15]=[C:16]([N:21]2[CH2:25][CH2:24][CH2:23][CH:22]2[C:26]2[CH:27]=[C:28]([C:43]([OH:45])=O)[CH:29]=[C:30]3[C:35]=2[O:34][C:33]([N:36]2[CH2:41][CH2:40][O:39][CH2:38][CH2:37]2)=[CH:32][C:31]3=[O:42])[CH:17]=[C:18]([F:20])[CH:19]=1.OC1C=CC=C[N+]=1[O-].[NH:54]1[CH2:59][CH2:58][O:57][CH2:56][CH2:55]1>C(Cl)Cl>[F:20][C:18]1[CH:17]=[C:16]([N:21]2[CH2:25][CH2:24][CH2:23][CH:22]2[C:26]2[CH:27]=[C:28]([C:43]([N:54]3[CH2:59][CH2:58][O:57][CH2:56][CH2:55]3)=[O:45])[CH:29]=[C:30]3[C:35]=2[O:34][C:33]([N:36]2[CH2:37][CH2:38][O:39][CH2:40][CH2:41]2)=[CH:32][C:31]3=[O:42])[CH:15]=[C:14]([F:13])[CH:19]=1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 866724028-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylic acidHCID 178526252HCID 178526252, compound

Product 1

HCID 665592448-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-6-(morpholine-4-carbonyl)-2-morpholino-4H-chromen-4-oneYield 59.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (71.4 mg, 0.37 mmol) was added portionwise to a stirred solution of 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid (85 mg, 0.19 mmol), 2-hydroxypyridine 1-oxide (41.4 mg, 0.37 mmol) and morpholine (0.033 mL, 0.37 mmol) at room temperature under nitrogen and stirred for 4 h. The reaction mixture was diluted with DCM, washed with water, brine, dried over MgSO4 and concentrated. The reaction mixture was purified by preparative HPLC. The fractions were evaporated to dryness, and the residue was dissolved in DCM, dried over MgSO4 and concentrated. The remaining solid was triturated with diethyl ether, filtered, washed with diethyl ether and dried under vacuum at 50° C. to afford 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-6-(morpholine-4-carbonyl)-2-morpholino-4H-chromen-4-one (58.0 mg, 59.3%) as a pale beige solid.

Workup

  1. washwashed with water, brine
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated
  4. customThe reaction mixture was purified by preparative HPLC
  5. customThe fractions were evaporated to dryness
  6. dissolutionthe residue was dissolved in DCM
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe remaining solid was triturated with diethyl ether
  10. filtrationfiltered
  11. washwashed with diethyl ether
  12. customdried under vacuum at 50° C.

Sources & evidence

ORD record
ord-fa8a1adb826f4dc6bfb3f2c1bacc744d
Source dataset
uspto-grants-2013_09
Patent number
US08530470B2

Reaction notes

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