Methanol → HCID 118590573, compound

HRID 1054473Notes

Reaction equation

HRID 1054473 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH: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.Br[CH2:30][C:31]([C:33]1[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=1)=[O:32].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[CH:9]1[CH2:13][CH2:12][CH2:11][N:10]1[C:14]1[CH:15]=[CH:16][C:17]2[N:18]([C:30]([C:31]([C:33]3[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=3)=[O:32])=[CH:21][N:20]=2)[CH:19]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 78373Dimethylformamide dimethyl acetalHCID 967492-Bromo-1-(4-fluorophenyl)ethan-1-oneHCID 118590408HCID 118590408, compound

Product 1

HCID 118590573HCID 118590573, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

To stirred solution of 5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyridin-2-amine (0.3 g, 1.0 mmol) (from Int-15) in dry toluene (3 ml, 10 v) was added DMF-DMA (0.14 g, 1.2 mmol) under N2 atm and stirred for 2 h at 120° C., after completion of starting material; cooled it to 10° C. then added 2-bromo-1-(4-fluorophenyl)ethanone (0.3 g, 1.4 mmol) drop wise and methanol (1 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 under vacuum and residue was dissolved in DCM (100 ml), washed with water, brine and dried over Na2SO4 and concentrated under vacuum to get crude product. Crude was purified by column chromatography using 60-120 mesh silica gel product eluted with 30-40% ethyl acetate/Hexane to afford (6-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)imidazo[1,2-a]pyridin-3-yl)(4-fluorophenyl)methanone as a off white solid (0.02 g, 4.3% Yield), MS (ESI): m/z 423.1 (M+H). 1H NMR (300 MHz, CDCl3) δ 9.08 (1H, s), 8.04 (1H, s), 7.89-7.84 (2H, m), 7.59-7.56 (1H, d J=9 Hz), 7.23-7.17 (2H, m), 7.09-7.08 (1H, m), 6.96-6.92 (2H, m), 6.81 (1H, bs), 5.07-5.04 (1H, d J=9 Hz), 3.85-3.75 (1H, m), 3.49-3.47 (1H, m), 2.54-2.46 (1H, m), 2.14-2.08 (3H, m) ppm.

Workup

  1. temperaturecooled 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 under vacuum and residue
  6. dissolutionwas dissolved in DCM (100 ml)
  7. washwashed with water, brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated under vacuum
  10. customto get crude product
  11. customCrude was purified by column chromatography
  12. washeluted with 30-40% ethyl acetate/Hexane

Sources & evidence

ORD record
ord-8b5bd8a15fd847b2bc35e09e27a83437
Source dataset
uspto-grants-2016_07
Patent number
US09394305B2

Reaction notes

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