Potassium Phosphate, Tribasic → 6-chloro-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

HRID 525692Notes

Reaction equation

HRID 525692 reaction equation
[O-]P([O-])([O-])=O.[K+].[K+].[K+].[O:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH:10]1[N:15]1[C:19](B2OC(C)(C)C(C)(C)O2)=[CH:18][CH:17]=[N:16]1.[Cl:29][C:30]1[C:49](I)=[CH:48][C:33]([C:34]([NH:36][C:37]2[CH:42]=[CH:41][C:40]([O:43][C:44]([F:47])([F:46])[F:45])=[CH:39][CH:38]=2)=[O:35])=[CH:32][N:31]=1>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:29][C:30]1[C:49]([C:19]2[N:15]([CH:10]3[CH2:11][CH2:12][CH2:13][CH2:14][O:9]3)[N:16]=[CH:17][CH:18]=2)=[CH:48][C:33]([C:34]([NH:36][C:37]2[CH:38]=[CH:39][C:40]([O:43][C:44]([F:45])([F:46])[F:47])=[CH:41][CH:42]=2)=[O:35])=[CH:32][N:31]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 115872081-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 867025996-chloro-5-iodo-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 899080896-chloro-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

K3PO4 (5.70 g, 26.8 mmol), followed by 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (3.73 g, 13.42 mmol) and Pd(PPh3)4 (0.517 g, 0.447 mmol) were added to a solution of 6-chloro-5-iodo-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 32.2, 4.0 g, 8.95 mmol) in toluene (45 mL) under an argon atmosphere. The RM was stirred at 80° C. for 5 h, filtered through Hyflo®, washed with EtOAc (100 mL) and the solvent was evaporated off under reduced pressure to give a crude product was purified by flash chromatography (Silica gel column, 80 g, n-hexane/EtOAc from 9:1 to 1:1) and triturated under n-hexane, filtered and dried to afford the title compound as a beige solid. HPLC (Condition 7) tR=7.569 min, UPLC-MS (Condition 3) tR=1.19 min, m/z=466.9 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.38-1.67 (m, 3H) 1.81-2.01 (m, 2H) 2.25-2.39 (m, 1H) 3.34-3.46 (m, 1H) 3.74-3.84 (m, 1H) 5.15 (d, J=8.21 Hz, 1H) 6.62 (s, 1H) 7.40 (d, J=8.21 Hz, 2H) 7.69 (s, 1H) 7.88 (d, J=8.99 Hz, 2H) 8.50 (s, 1H) 9.06 (s, 1H) 10.70 (s, 1H).

Workup

  1. filtrationfiltered through Hyflo®
  2. washwashed with EtOAc (100 mL)
  3. customthe solvent was evaporated off under reduced pressure
  4. customto give a crude product
  5. customwas purified by flash chromatography (Silica gel column, 80 g, n-hexane/EtOAc from 9:1 to 1:1)
  6. customtriturated under n-hexane
  7. filtrationfiltered
  8. customdried

Sources & evidence

ORD record
ord-f573591c64d34c00b8e7afbc47c10bdb
Source dataset
uspto-grants-2016_05
Patent number
US09340537B2

Reaction notes

Loading…