Water → 6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(4-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)nicotinamide

HRID 73807Notes

Reaction equation

HRID 73807 reaction equation
[O-]P([O-])([O-])=O.[K+].[K+].[K+].[Cl:9][C:10]1[C:29](I)=[CH:28][C:13]([C:14]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][C:24]([Cl:27])([F:26])[F:25])=[CH:19][CH:18]=2)=[O:15])=[CH:12][N:11]=1.[CH3:31][C:32]1[CH:33]=[N:34][N:35]([CH:46]2[CH2:51][CH2:50][CH2:49][CH2:48][O:47]2)[C:36]=1B1OC(C)(C)C(C)(C)O1.O>C1(C)C=CC=CC=1.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:9][C:10]1[C:29]([C:36]2[N:35]([CH:46]3[CH2:51][CH2:50][CH2:49][CH2:48][O:47]3)[N:34]=[CH:33][C:32]=2[CH3:31])=[CH:28][C:13]([C:14]([NH:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][C:24]([Cl:27])([F:26])[F:25])=[CH:19][CH:18]=2)=[O:15])=[CH:12][N:11]=1

Participants

7

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 547724154-methyl-1-(oxan-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 867026266-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-iodonicotinamide

Product 1

HCID 867026356-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(4-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)nicotinamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

K3PO4 (191 mg, 0.9 mmol) and Pd(PPh3)4 (17.33 mg, 0.015 mmol) were added to a solution of 6-Chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-iodonicotinamide (Stage 25.2, 138 mg, 0.3 mmol) and 4-methyl-1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (131 mg, 0.45 mmol) in toluene (1.5 mL) under an argon atmosphere in a vial, which was sealed and heated at 110° C. for 18 h. The RM was poured into 20 mL water and extracted with EtOAc. The combined extracts were dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a residue which was purified by flash chromatography (RediSep® Silica gel column, n-heptane/EtOAc, from 5 to 50% EtOAc) and crystallized from n-heptane to afford the title compound as an off-white powder. HPLC (Condition 4) tR=6.8 min, UPLC-MS (Condition 3) tR=1.26 min, m/z=495 [M−H]−.

Workup

  1. customwas sealed
  2. extractionextracted with EtOAc
  3. dry with materialThe combined extracts were dried over Na2SO4
  4. customthe solvent was evaporated off under reduced pressure
  5. customto give a residue which
  6. customwas purified by flash chromatography (RediSep® Silica gel column, n-heptane/EtOAc, from 5 to 50% EtOAc)
  7. customcrystallized from n-heptane

Sources & evidence

ORD record
ord-5f25c43e77f04347bdbb7b71dbd27b56
Source dataset
uspto-grants-2014_09
Patent number
US08829195B2

Reaction notes

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