4-fluoro-5-(tributylstannyl)-1H-pyrazole → 6-chloro-5-(4-fluoro-1H-pyrazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 73740Notes

Reaction equation

HRID 73740 reaction equation
[Cl:1][C:2]1[C:21](I)=[CH:20][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:18])[F:17])=[CH:11][CH:10]=2)=[O:7])=[CH:4][N:3]=1.[F:23][C:24]1[CH:25]=[N:26][NH:27][C:28]=1[Sn](CCCC)(CCCC)CCCC>CS(C)=O.CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[C:21]([C:28]2[NH:27][N:26]=[CH:25][C:24]=2[F:23])=[CH:20][C:5]([C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][C:16]([F:19])([F:18])[F:17])=[CH:11][CH:10]=2)=[O:7])=[CH:4][N:3]=1

Participants

6

Reactant 2

HCID 111530444-fluoro-5-(tributylstannyl)-1H-pyrazoleHCID 867025996-chloro-5-iodo-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 867026006-chloro-5-(4-fluoro-1H-pyrazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

Pd(Ph3P)4 (17.33 mg, 0.015 mmol) was added to solution of 6-chloro-5-iodo-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 4.2, 133 mg, 0.3 mmol) and 4-fluoro-5-(tributylstannyl)-1H-pyrazole (101 mg, 0.270 mmol) in DMSO (1 mL) in a vial under an argon atmosphere. The vial was sealed and the RM mixture was heated at 100° C. for 18 h. After cooling to RT, the RM was dissolved in EtOAc, washed with brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give the crude product which was purified by flash chromatography (RediSep® Silica gel column, n-heptane/EtOAc from 10% to 50% EtOAc) to afford the title compound as an off-white powder. HPLC (Condition 4) tR=5.5 min, UPLC-MS (Condition 3) tR=1.05 min, m/z=399.2 [M−H]−.

Workup

  1. customThe vial was sealed
  2. temperatureAfter cooling to RT
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. customthe solvent was evaporated off under reduced pressure
  6. customto give the crude product which
  7. customwas purified by flash chromatography (RediSep® Silica gel column, n-heptane/EtOAc from 10% to 50% EtOAc)

Sources & evidence

ORD record
ord-e7199899ea914bf7abeed5e2aeab00bc
Source dataset
uspto-grants-2014_09
Patent number
US08829195B2

Reaction notes

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