Water → 2-chloro-N-(3-cyano-1-phenyl-1H-pyrazol-5-yl)-5-(3-fluoropyridin-2-yl)benzamide

HRID 522103Notes

Reaction equation

[Cl:1][C:2]1[CH:23]=[CH:22][C:21](B2OC(C)(C)C(C)(C)O2)=[CH:20][C:3]=1[C:4]([NH:6][C:7]1[N:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:10]=[C:9]([C:18]#[N:19])[CH:8]=1)=[O:5].[F:33][C:34]1[C:35](I)=[N:36][CH:37]=[CH:38][CH:39]=1.C([O-])([O-])=O.[K+].[K+].O>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:1][C:2]1[CH:23]=[CH:22][C:21]([C:35]2[C:34]([F:33])=[CH:39][CH:38]=[CH:37][N:36]=2)=[CH:20][C:3]=1[C:4]([NH:6][C:7]1[N:11]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:10]=[C:9]([C:18]#[N:19])[CH:8]=1)=[O:5]

Participants

Conditions

Temperature: 100 °C

Procedure

To a degassed solution of 2-chloro-N-(3-cyano-1-phenyl-1H-pyrazol-5-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (Preparation 7, 223 mg, 0.49 mmol) in dioxane (2 mL) was added 3-fluoro-2-iodopyridine (167 mg, 0.75 mmol), Pd(dppf)Cl2 (36 mg, 0.049 mmol), K2CO3 (206 mg, 1.49 mmol) and water (1 mL). The reaction was heated at 100° C. for 18 hours before cooling and concentrating in vacuo. The residue was suspended in DCM (20 mL) and filtered through a pad of celite. The filtrate was purified directly by silica gel column chromatography eluting with 0-80% EtOAc in heptanes to afford the title compound as a brown solid (100 mg, 48%).

Workup

temperaturebefore cooling
concentrationconcentrating in vacuo
filtrationfiltered through a pad of celite
customThe filtrate was purified directly by silica gel column chromatography
washeluting with 0-80% EtOAc in heptanes

Sources & evidence

ORD record: ord-2d0f65d3147742008f67c689053d70b6
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328096B2

Reaction notes

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