4-fluoro-5-(tributylstannyl)-1H-pyrazole → N-(4-(Chlorodifluoromethoxy)phenyl)-5-(4-fluoro-1H-pyrazol-5-yl)-6-(3-hydroxyazetidin-1-yl)nicotinamide

HRID 525765Notes

Reaction equation

HRID 525765 reaction equation
[Cl:1][C:2]([F:26])([F:25])[O:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:24])[C:12]2[CH:17]=[C:16](I)[C:15]([N:19]3[CH2:22][CH:21]([OH:23])[CH2:20]3)=[N:14][CH:13]=2)=[CH:6][CH:5]=1.[F:27][C:28]1[CH:29]=[N:30][NH:31][C:32]=1[Sn](CCCC)(CCCC)CCCC>>[Cl:1][C:2]([F:26])([F:25])[O:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:24])[C:12]2[CH:17]=[C:16]([C:32]3[NH:31][N:30]=[CH:29][C:28]=3[F:27])[C:15]([N:19]3[CH2:22][CH:21]([OH:23])[CH2:20]3)=[N:14][CH:13]=2)=[CH:6][CH:5]=1

Participants

3

Reactant 2

HCID 111530444-fluoro-5-(tributylstannyl)-1H-pyrazoleHCID 89906873N-(4-(chlorodifluoromethoxy)phenyl)-6-(3-hydroxyazetidin-1-yl)-5-iodonicotinamide

Product 1

HCID 118045004N-(4-(Chlorodifluoromethoxy)phenyl)-5-(4-fluoro-1H-pyrazol-5-yl)-6-(3-hydroxyazetidin-1-yl)nicotinamide

Procedure

The title compound was prepared in an analogous fashion to that described in Example 92 using N-(4-(chlorodifluoromethoxy)phenyl)-6-(3-hydroxyazetidin-1-yl)-5-iodonicotinamide (Stage 88.1) and 4-fluoro-5-(tributylstannyl)-1H-pyrazole. After purification by flash chromatography on silica gel, the residue was dissolved in MeCN (2 mL), sonicated and then stirred at RT for 90 min. The resulting suspension was filtered, washed with MeCN (3 mL) and dried to afford the title product as a white solid. HPLC (Condition 7) tR=5.72 min, UPLC-MS (Condition 8) tR=0.93 min, m/z=454.1 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 3.53-3.61 (m, 2H) 3.91-4.01 (m, 2H) 4.37-4.47 (m, 1H) 5.57 (br. s, 1H) 7.33 (d, J=8.99 Hz, 2H) 7.83-7.97 (m, 3H) 8.04 (d, J=1.96 Hz, 1H) 8.78 (d, J=1.96 Hz, 1H) 10.23 (br. s, 1H) 13.03 (br. s, 1H).

Workup

  1. customThe title compound was prepared in an analogous fashion to
  2. customAfter purification by flash chromatography on silica gel
  3. dissolutionthe residue was dissolved in MeCN (2 mL)
  4. customsonicated
  5. filtrationThe resulting suspension was filtered
  6. washwashed with MeCN (3 mL)
  7. customdried

Sources & evidence

ORD record
ord-ade515e98479442ea4ab44ad0469e124
Source dataset
uspto-grants-2016_05
Patent number
US09340537B2

Reaction notes

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