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

HRID 41165

Reaction equation

HRID 41165 reaction equation
C[CH2:2][N:3](C(C)C)[CH:4](C)C.[F:10][C:11]1[CH:12]=[C:13]([N:18]2[CH2:22][CH2:21][CH2:20][CH:19]2[C:23]2[CH:24]=[C:25]([C:40](O)=[O:41])[CH:26]=[C:27]3[C:32]=2[O:31][C:30]([N:33]2[CH2:38][CH2:37][O:36][CH2:35][CH2:34]2)=[CH:29][C:28]3=[O:39])[CH:14]=[C:15]([F:17])[CH:16]=1.[B-](F)(F)(F)F.CN(C(ON1C(=O)CCC1=O)=[N+](C)C)C.CNC>CN(C=O)C>[F:17][C:15]1[CH:14]=[C:13]([N:18]2[CH2:22][CH2:21][CH2:20][CH:19]2[C:23]2[CH:24]=[C:25]([C:40]([N:3]([CH3:4])[CH3:2])=[O:41])[CH:26]=[C:27]3[C:32]=2[O:31][C:30]([N:33]2[CH2:38][CH2:37][O:36][CH2:35][CH2:34]2)=[CH:29][C:28]3=[O:39])[CH:12]=[C:11]([F:10])[CH:16]=1

Participants

6

Reactant 4

HCID 674DimethylamineHCID 81531DiisopropylethylamineHCID 98575222-(2,5-Dioxopyrrolidin-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborateHCID 866724028-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid

Product 1

HCID 665592438-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamideYield 68.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

DIPEA (0.046 mL, 0.26 mmol) was added to a suspension of 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylic acid (60 mg, 0.13 mmol) in DMF (1 mL) followed by TSTU (43.5 mg, 0.14 mmol) at room temperature under nitrogen and stirred overnight. Dimethylamine (2N in THF) (0.131 mL, 0.26 mmol) was then added and the mixture was stirred for another hour. The reaction mixture was purified by preparative HPLC. The fractions were evaporated to dryness, the residue was taken up in a minimum of DCM, diluted with petroleum ether, stirred for 3 h, collected by filtration and dried to afford 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (43 mg, 68%) as a white solid.

Workup

  1. stirringthe mixture was stirred for another hour
  2. customThe reaction mixture was purified by preparative HPLC
  3. customThe fractions were evaporated to dryness
  4. additiondiluted with petroleum ether
  5. stirringstirred for 3 h
  6. filtrationcollected by filtration
  7. customdried

Sources & evidence

ORD record
ord-88b8afdafbdc459ba5898bdf1e8dce85
Source dataset
uspto-grants-2013_09
Patent number
US08530470B2

Linked notes

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