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

HRID 41212Notes

Reaction equation

HRID 41212 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:54](O)=[O:55])[CH:39]=[C:40]3[C:45]=2[O:44][C:43]([N:46]2[CH2:51][CH2:50][O:49][C@H:48]([CH3:52])[CH2:47]2)=[CH:42][C:41]3=[O:53])[CH:27]=[C:28]([F:30])[CH:29]=1.CCN(C(C)C)C(C)C.[NH:66]1[CH2:71][CH2:70][O:69][CH2:68][CH2:67]1>CC(N(C)C)=O>[F:30][C:28]1[CH:27]=[C:26]([N:31]2[CH2:35][CH2:34][CH2:33][CH:32]2[C:36]2[CH:37]=[C:38]([C:54]([N:66]3[CH2:71][CH2:70][O:69][CH2:68][CH2:67]3)=[O:55])[CH:39]=[C:40]3[C:45]=2[O:44][C:43]([N:46]2[CH2:51][CH2:50][O:49][C@H:48]([CH3:52])[CH2:47]2)=[CH:42][C:41]3=[O:53])[CH:25]=[C:24]([F:23])[CH:29]=1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 866724358-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-((R)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxylic acid

Product 1

HCID 665581388-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-((R)-2-methylmorpholino)-6-(morpholine-4-carbonyl)-4H-chromen-4-oneYield 66.3%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

TBTU (154 mg, 0.48 mmol) was added to a stirred solution of 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-((R)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxylic acid (90 mg, 0.19 mmol), DIPEA (0.083 mL, 0.48 mmol) dissolved in DMA (2 mL) under nitrogen. The resulting solution was stirred at room temperature for 30 min. Morpholine (0.050 mL, 0.57 mmol) was added and the mixture was stirred at room temperature for 1 h. The reaction mixture was purified by preparative HPLC. The fractions containing the desired compound were evaporated to dryness to afford 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-((R)-2-methylmorpholino)-6-(morpholine-4-carbonyl)-4H-chromen-4-one (68 mg, 66%) as a yellow solid.

Workup

  1. stirringthe mixture was stirred at room temperature for 1 h
  2. customThe reaction mixture was purified by preparative HPLC
  3. additionThe fractions containing the desired compound
  4. customwere evaporated to dryness

Sources & evidence

ORD record
ord-b8b71fd715704506924531ca712a58a6
Source dataset
uspto-grants-2013_09
Patent number
US08530470B2

Reaction notes

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