Dimethylformamide → HCID 117993109, compound

HRID 922590Notes

Reaction equation

HRID 922590 reaction equation
C[O:2][C:3]1[C:8]([C@@:9]2([CH3:15])[CH2:13][CH2:12][NH:11][C:10]2=[O:14])=[CH:7][CH:6]=[C:5]([C:16]2[CH:17]=[C:18]3[C:22](=[CH:23][CH:24]=2)[N:21]([CH3:25])[CH:20]=[CH:19]3)[N:4]=1.C([S-])CC.[Na+].CN(C=O)C>CCO>[CH3:25][N:21]1[C:22]2[C:18](=[CH:17][C:16]([C:5]3[NH:4][C:3](=[O:2])[C:8]([C@@:9]4([CH3:15])[CH2:13][CH2:12][NH:11][C:10]4=[O:14])=[CH:7][CH:6]=3)=[CH:24][CH:23]=2)[CH:19]=[CH:20]1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 46817251-Propanethiol, sodium salt (1:1)2×HCID 117993486HCID 117993486, compound

Product 1

HCID 117993109HCID 117993109, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
110 °C

Procedure

To a flask was added (R)-3-(2-methoxy-6-(1-methyl-1H-indol-5-yl)pyridin-3-yl)-3-methylpyrrolidin-2-one (534 mg, 1.59 mmol), sodium n-propanethiolate (1287 mg, 13.11 mmol), and DMF (9.5 mL). The mixture was stirred for 17 h at 110° C. Due to incomplete reaction, additional sodium n-propanethiolate (667 mg) was added. The reaction was stirred for 30 h at 110° C. The mixture was diluted with EtOH, concentrated and partitioned between 15% EtOH/DCM and pH 7 phosphate buffer. The aqueous phase was extracted 2× and the combined organic layers were dried over Na2SO4 to provide a crude product. Purification by slurrying at r.t. overnight (3.3 mL EtOAc/0.33 mL EtOH) followed by filtration, wash with EtOAc several times and dried under reduced pressure for 3 days at 60-80° C. provided (R)-6-(1-methyl-1H-indol-5-yl)-3-(3-methyl-2-oxopyrrolidin-3-yl)pyridin-2(1H)-one (495 mg, 97%) as a yellow solid. 1H NMR (600 MHz, methanol-d4) δ: 1.54 (s, 3H), 1.91-1.98 (m, 1H), 2.68-2.79 (m, 1H), 3.48 (dd, 2H), 3.85 (s, 3H), 6.55 (d, 1H), 6.62 (d, 1H), 7.26 (d, 1H), 7.47 (dd, 1H), 7.49-7.51 (m, 1H), 7.63 (d, 1H), 7.89 (d, 1H); MS (ES+)(M+H) 322.

Workup

  1. additionwas added
  2. stirringThe reaction was stirred for 30 h at 110° C
  3. concentrationconcentrated
  4. custompartitioned between 15% EtOH/DCM and pH 7 phosphate buffer
  5. extractionThe aqueous phase was extracted 2×
  6. dry with materialthe combined organic layers were dried over Na2SO4
  7. customto provide a crude product
  8. customPurification
  9. waitby slurrying at r.t. overnight
  10. filtration(3.3 mL EtOAc/0.33 mL EtOH) followed by filtration
  11. washwash with EtOAc several times
  12. customdried under reduced pressure for 3 days at 60-80° C.

Sources & evidence

ORD record
ord-1dc1420c70244fc7a28d640e0d4f6f35
Source dataset
uspto-grants-2016_03
Patent number
US09278953B2

Reaction notes

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