Methanol → HCID 118595411, compound

HRID 1054437Notes

Reaction equation

HRID 1054437 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@H:9]1[CH2:13][CH2:12][CH2:11][N:10]1[C:14]1[CH:15]=[CH:16][C:17]([NH2:20])=[N:18][CH:19]=1.[CH3:21]N(C(OC)OC)C.[CH2:29]([O:31][C:32](=[O:35])[CH2:33]Br)[CH3:30].CO>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@H:9]1[CH2:13][CH2:12][CH2:11][N:10]1[C:14]1[CH:15]=[CH:16][C:17]2[N:18]([C:33]([C:32]([O:31][CH2:29][CH3:30])=[O:35])=[CH:21][N:20]=2)[CH:19]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 7748Ethyl bromoacetateHCID 78373Dimethylformamide dimethyl acetalHCID 118590405HCID 118590405, compound

Product 1

HCID 118595411HCID 118595411, compoundYield 61.8%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

To stirred solution of (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyridin-2-amine (2.7 g, 9.8 mmol) in dry toluene (27 ml, 10 v) was added DMF-DMA (2.45 g, 20.61 mmol) under N2 atm and stirred for 2 h at 120° C. during which complete consumption of Int-12 was observed by TLC, cool it to 10° C. then added Ethylbromoacetate (3.6 g, 21.59 mmol) drop wise and methanol (2 ml) was added under N2 atm then stirred for 16 h at 120° C. Reaction mixture was cooled to room temperature and solvent was removed in vacuo and residue was dissolved in DCM (200 ml), washed with water and brine, dried over anhydrous Na2SO4 and concentrated under vacuum to get crude product. Crude was purified by column chromatography (eluted with 30-40% ethyl acetate/Hexane) to afford pale green solid (2.25 g, 61.8% yield), MS (ESI): m/z 372.1 (M+H); 1H NMR (400 MHz, CDCl3) δ 8.57-8.56 (1H, m), 8.17 (1H, s), 7.51-7.49 (1H, dd), 7.08-7.04 (1H, m), 6.92-6.91 (1H, m), 6.84-6.80 (2H, m), 5.02-5.00 (1H, m), 4.40-4.35 (2H, q), 3.74-3.72 (1H, m), 3.43-3.42 (1H, m), 2.48-2.46 (1H, m), 2.12-2.02 (3H, m), 1.43-1.37 (3H, t) ppm.

Workup

  1. temperaturecool it to 10° C.
  2. stirringatm then stirred for 16 h at 120° C
  3. customReaction mixture
  4. temperaturewas cooled to room temperature
  5. customsolvent was removed in vacuo and residue
  6. dissolutionwas dissolved in DCM (200 ml)
  7. washwashed with water and brine
  8. dry with materialdried over anhydrous Na2SO4
  9. concentrationconcentrated under vacuum
  10. customto get crude product
  11. customCrude was purified by column chromatography (eluted with 30-40% ethyl acetate/Hexane)

Sources & evidence

ORD record
ord-fcca217682ab4ec18493c764752adaf2
Source dataset
uspto-grants-2016_07
Patent number
US09394305B2

Reaction notes

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