Hydrochloric Acid → HCID 117771050, compound

HRID 2201533Notes

Reaction equation

HRID 2201533 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:20]=[C:19]([N:21]([CH3:26])[S:22]([CH3:25])(=[O:24])=[O:23])[C:18]([C:27]4[N:32]=[C:31]([C:33]([NH:35][CH2:36][C:37]5[CH:42]=[CH:41][C:40]([F:43])=[CH:39][N:38]=5)=[O:34])[C:30]([O:44]C)=[CH:29][CH:28]=4)=[CH:17][C:11]=3[C:12]=2[C:13](=[O:16])[NH:14][CH3:15])=[CH:4][CH:3]=1.Cl>CN(C=O)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:9][C:10]3[CH:20]=[C:19]([N:21]([CH3:26])[S:22]([CH3:25])(=[O:24])=[O:23])[C:18]([C:27]4[N:32]=[C:31]([C:33]([NH:35][CH2:36][C:37]5[CH:42]=[CH:41][C:40]([F:43])=[CH:39][N:38]=5)=[O:34])[C:30]([OH:44])=[CH:29][CH:28]=4)=[CH:17][C:11]=3[C:12]=2[C:13](=[O:16])[NH:14][CH3:15])=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 117771043HCID 117771043, compound

Product 1

HCID 117771050HCID 117771050, compoundYield 64.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a stirring solution of 6-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)-N-((5-fluoropyridin-2-yl)methyl)-3-methoxypicolinamide (40 mg, 0.05 mmol) in DMF (5 mL) was added Py.HCl (400 mg, 2.22 mmol) under N2 protection. The mixture was stirred in a pre-heated oil-bath at 100° C. for 10 h. The mixture was concentrated in vacuo, diluted with water and extracted with EtOAc. After being washed with brine, dried over Na2SO4, filtered and evaporated, the crude product was purified by prep-TLC (PE:EtOAc=2:1) to give the product of 6-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-(N-methylmethylsulfonamido)benzofuran-5-yl)-N-((5-fluoropyridin-2-yl)methyl)-3-hydroxypicolinamide (20 mg, yield: 58%). 1H-NMR (CDCl3, 400 MHz) δ 12.14 (s, 1H), 8.91 (d, J=5.6 Hz, 1H), 8.33 (s, 1H), 7.94 (s, 1H), 7.86˜7.89 (m, 2H), 7.60 (d, J=8.8 Hz, 1H), 7.52 (s, 1H), 7.36 (d, J=8.8 Hz, 1H), 7.31˜7.33 (m, 2H), 7.15 (d, J=8.8 Hz, 2H), 5.78 (d, J=4.0 Hz, 1H), 4.68 (d, J=5.6 Hz, 2H), 3.12 (s, 3H), 2.92 (d, J=4.8 Hz, 3H), 2.76 (s, 3H). MS (M+H)+: 622.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. additiondiluted with water
  3. extractionextracted with EtOAc
  4. washAfter being washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customthe crude product was purified by prep-TLC (PE:EtOAc=2:1)

Sources & evidence

ORD record
ord-c6ec3cea2d334802b8eee33bc6e49ab2
Source dataset
uspto-grants-2016_06
Patent number
US09364482B2

Reaction notes

Loading…