Morpholine → HCID 66559245, compound

HRID 41183Notes

Reaction equation

HRID 41183 reaction equation
[B-](F)(F)(F)F.CN(C(ON1C(=O)CCC1=O)=[N+](C)C)C.[F:21][C:22]1[CH:23]=[C:24]([N:29]2[CH2:33][CH2:32][CH2:31][C@H:30]2[C:34]2[CH:35]=[C:36]([C:51]([OH:53])=O)[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])[CH:25]=[C:26]([F:28])[CH:27]=1.CCN(C(C)C)C(C)C.[NH:63]1[CH2:68][CH2:67][O:66][CH2:65][CH2:64]1>>[F:28][C:26]1[CH:25]=[C:24]([N:29]2[CH2:33][CH2:32][CH2:31][C@H:30]2[C:34]2[CH:35]=[C:36]([C:51]([N:63]3[CH2:68][CH2:67][O:66][CH2:65][CH2:64]3)=[O:53])[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])[CH:23]=[C:22]([F:21])[CH:27]=1

Participants

5

Reactant 4

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 98575222-(2,5-Dioxopyrrolidin-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborateHCID 86672409HCID 86672409, compound

Product 1

HCID 66559245HCID 66559245, compoundYield 57%

Procedure

TSTU (75.0 mg, 0.23 mmol) was added in one portion to a stirred solution of 8-[(2S)-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)]-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid (102 mg, 0.21 mmol, >98% enantiomeric purity, made from the first eluting ester enantiomer from chiral separation of tert-butyl 2-(6-(methoxycarbonyl)-2-morpholino-4-oxo-4H-chromen-8-yl)pyrrolidine-1-carboxylate—see below) and DIPEA (0.041 mL, 0.23 mmol) at room temperature The resulting mixture was stirred at room temperature for 1.5 h. Morpholine (0.037 mL, 0.42 mmol) was then added to the reaction mixture and stirring was continued over the week-end. The reaction mixture was purified by preparative HPLC. The fractions were evaporated to dryness, 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-[(2S)-1-(3,5-difluorophenyl)pyrrolidin-2-yl]-6-(morpholine-4-carbonyl)-2-morpholino-4H-chromen-4-one (64 mg, 57%) as a pale yellow solid.

Workup

  1. washfirst eluting ester enantiomer
  2. customfrom chiral separation of tert-butyl 2-(6-(methoxycarbonyl)-2-morpholino-4-oxo-4H-chromen-8-yl)pyrrolidine-1-carboxylate—
  3. customat room temperature
  4. stirringstirring
  5. customThe reaction mixture was purified by preparative HPLC
  6. customThe fractions were evaporated to dryness
  7. dissolutionthe residue was dissolved in DCM
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. customThe remaining solid was triturated with diethyl ether
  11. filtrationfiltered
  12. washwashed with diethyl ether
  13. customdried under vacuum at 50° C.

Sources & evidence

ORD record
ord-49973a5c091346e5823084c168d447eb
Source dataset
uspto-grants-2013_09
Patent number
US08530470B2

Reaction notes

Loading…