Morpholine → HCID 66558056, compound

HRID 41194Notes

Reaction equation

HRID 41194 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:28]2[CH2:32][CH2:31][CH2:30][C@@H:29]2[C:33]2[CH:34]=[C:35]([C:50](O)=[O:51])[CH:36]=[C:37]3[C:42]=2[O:41][C:40]([N:43]2[CH2:48][CH2:47][O:46][CH2:45][CH2:44]2)=[CH:39][C:38]3=[O:49])[CH:25]=[CH:26][CH:27]=1.[NH:53]1[CH2:58][CH2:57][O:56][CH2:55][CH2:54]1.CCN(C(C)C)C(C)C>C(Cl)Cl>[F:21][C:22]1[CH:23]=[C:24]([N:28]2[CH2:32][CH2:31][CH2:30][C@@H:29]2[C:33]2[CH:34]=[C:35]([C:50]([N:53]3[CH2:58][CH2:57][O:56][CH2:55][CH2:54]3)=[O:51])[CH:36]=[C:37]3[C:42]=2[O:41][C:40]([N:43]2[CH2:48][CH2:47][O:46][CH2:45][CH2:44]2)=[CH:39][C:38]3=[O:49])[CH:25]=[CH:26][CH:27]=1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 98575222-(2,5-Dioxopyrrolidin-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborateHCID 866724198-[(2R)-(1-(3-fluorophenyl)pyrrolidin-2-yl)]-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid

Product 1

HCID 66558056HCID 66558056, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TSTU (220 mg, 0.68 mmol) was added in one portion to a stirred suspension of 8-[(2R)-(1-(3-fluorophenyl)pyrrolidin-2-yl)]-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid (250 mg, 0.57 mmol, >98% enantiomeric purity, see Example 1.06 for details of preparation), morpholine (0.075 mL, 0.86 mmol) and DIPEA (0.149 mL, 0.86 mmol) dissolved in DCM (5 mL) at room temperature under nitrogen. The resulting suspension was stirred at room temperature for 16 h. The reaction mixture was purified by preparative HPLC. The fractions were evaporated to dryness, the obtained foam was dissolved in DCM (0.5 mL) and diethyl ether (1 mL) was added. The resulting crystalline solid was collected by filtration and dried under vacuum to give 8-[(2R)-(1-(3-fluorophenyl)pyrrolidin-2-yl)]-6-(morpholine-4-carbonyl)-2-morpholino-4H-chromen-4-one (126 mg, 44%) as a white crystalline solid.

Workup

  1. customThe reaction mixture was purified by preparative HPLC
  2. customThe fractions were evaporated to dryness
  3. dissolutionthe obtained foam was dissolved in DCM (0.5 mL)
  4. additiondiethyl ether (1 mL) was added
  5. filtrationThe resulting crystalline solid was collected by filtration
  6. customdried under vacuum

Sources & evidence

ORD record
ord-059d7ef3cb954f0d8d467f9f0e8178c5
Source dataset
uspto-grants-2013_09
Patent number
US08530470B2

Reaction notes

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