4-Methylmorpholine → 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-N-(2-hydroxyethyl)-N-methyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide

HRID 41180Notes

Reaction equation

HRID 41180 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]2[CH2:35][CH2:34][CH2:33][CH:32]2[C:36]2[CH:37]=[C:38]([C:53]([OH:55])=O)[CH:39]=[C:40]3[C:45]=2[O:44][C:43]([N:46]2[CH2:51][CH2:50][O:49][CH2:48][CH2:47]2)=[CH:42][C:41]3=[O:52])[CH:27]=[C:28]([F:30])[CH:29]=1.[CH3:56][N:57]1CC[O:60][CH2:59][CH2:58]1.CNCCO>CN1C(=O)CCC1>[F:23][C:24]1[CH:25]=[C:26]([N:31]2[CH2:35][CH2:34][CH2:33][CH:32]2[C:36]2[CH:37]=[C:38]([C:53]([N:57]([CH2:58][CH2:59][OH:60])[CH3:56])=[O:55])[CH:39]=[C:40]3[C:45]=2[O:44][C:43]([N:46]2[CH2:51][CH2:50][O:49][CH2:48][CH2:47]2)=[CH:42][C:41]3=[O:52])[CH:27]=[C:28]([F:30])[CH:29]=1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 80162-(Methylamino)ethanolHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 866724028-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid

Product 1

HCID 866724078-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-N-(2-hydroxyethyl)-N-methyl-2-morpholino-4-oxo-4H-chromene-6-carboxamideYield 71.4%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

TBTU (102 mg, 0.32 mmol) was added to a stirred solution of 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid (105 mg, 0.21 mmol), 4-methylmorpholine (0.070 mL, 0.63 mmol) and 2-(methylamino)ethanol (0.022 mL, 0.28 mmol) dissolved in NMP (1.5 mL). The resulting solution was stirred at room temperature for 16 h then purified by preparative HPLC. The fractions were evaporated to dryness and triturated in diethyl ether to afford a solid. This material was collected by filtration, washed with diethyl ether and dried under vacuum at 50° C. to afford 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-N-(2-hydroxyethyl)-N-methyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (77 mg, 71%) as a white solid.

Workup

  1. customthen purified by preparative HPLC
  2. customThe fractions were evaporated to dryness
  3. customtriturated in diethyl ether
  4. customto afford a solid
  5. filtrationThis material was collected by filtration
  6. washwashed with diethyl ether
  7. customdried under vacuum at 50° C.

Sources & evidence

ORD record
ord-cf80b1b2cc91478aa981d2ca01c97ae6
Source dataset
uspto-grants-2013_09
Patent number
US08530470B2

Reaction notes

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