Dimethylamine, hydrochloride → (2R)-(1-(3-fluorophenyl)pyrrolidin-2-yl]-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide

HRID 41191Notes

Reaction equation

HRID 41191 reaction equation
[B-](F)(F)(F)[F:2].CN(C(ON1[C:19](=O)[CH2:18][CH2:17]C1=O)=[N+](C)C)C.FC1C=C(N2CCC[C@@H]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])C=CC=1.Cl.[CH3:54][NH:55][CH3:56].[CH3:57][CH2:58][N:59]([CH:63]([CH3:65])[CH3:64])[CH:60]([CH3:62])C>C(Cl)Cl>[F:2][C:17]1[CH:65]=[C:63]([N:59]2[CH2:58][CH2:57][CH2:62][C@@H:60]2[C:39]2[C:38](=[O:49])[C:37]3[C:42](=[CH:33][CH:34]=[C:35]([C:50]([N:55]([CH3:56])[CH3:54])=[O:51])[CH:36]=3)[O:41][C:40]=2[N:43]2[CH2:44][CH2:45][O:46][CH2:47][CH2:48]2)[CH:64]=[CH:19][CH:18]=1

Participants

6

Reactant 4

HCID 10473Dimethylamine, hydrochlorideHCID 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 131730839(2R)-(1-(3-fluorophenyl)pyrrolidin-2-yl]-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamideYield 53.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TSTU (429 mg, 1.34 mmol) was added in one portion to a stirred suspension of 8-[(2R)-1-(3-fluorophenyl)pyrrolidin-2-yl]-2-morpholino-4-oxo-chromene-6-carboxylic acid (488 mg, 1.11 mmol, >98% enantiomeric purity), dimethylamine hydrochloride (127 mg, 1.56 mmol) and DIPEA (0.582 mL, 3.34 mmol) dissolved in DCM (5 mL) at room temperature under nitrogen. The resulting suspension was stirred at room temperature for 20 min. The reaction mixture was quenched with water and extracted with DCM (1×40 mL). The organic phase was dried over MgSO4 and concentrated to afford the crude product as a yellow foam. The crude product was purified by flash chromatography on silica gel eluting with 0 to 10% MeOH in EtAc. The solvent was evaporated to dryness, the foam was triturated in diethyl ether (10 mL), the resulting solid was filtered and dried under reduced pressure to afford 8-[(2R)-(1-(3-fluorophenyl)pyrrolidin-2-yl]-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (276 mg, 53%) as a yellow solid.

Workup

  1. customThe reaction mixture was quenched with water
  2. extractionextracted with DCM (1×40 mL)
  3. dry with materialThe organic phase was dried over MgSO4
  4. concentrationconcentrated
  5. customto afford the crude product as a yellow foam
  6. customThe crude product was purified by flash chromatography on silica gel eluting with 0 to 10% MeOH in EtAc
  7. customThe solvent was evaporated to dryness
  8. customthe foam was triturated in diethyl ether (10 mL)
  9. filtrationthe resulting solid was filtered
  10. customdried under reduced pressure

Sources & evidence

ORD record
ord-765eea1a79094d2a8cd5f3421b9bb890
Source dataset
uspto-grants-2013_09
Patent number
US08530470B2

Reaction notes

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