Sodium Bicarbonate → 6-(4-(4-cyano-2-fluorophenyl)-5-methoxy-1H-pyrazol-1-yl)-N-(3-methoxypropyl)nicotinamide
Reaction equation
Br[C:2]1[CH:3]=[N:4][N:5]([C:9]2[CH:22]=[CH:21][C:12]([C:13]([NH:15][CH2:16][CH2:17][CH2:18][O:19][CH3:20])=[O:14])=[CH:11][N:10]=2)[C:6]=1[O:7][CH3:8].[F:23][C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][C:31]=1B1OC(C)(C)C(C)(C)O1)[C:27]#[N:28].C(=O)(O)[O-].[Na+]>O1CCOCC1.O.CCOC(C)=O.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].C(Cl)Cl>[C:27]([C:26]1[CH:29]=[CH:30][C:31]([C:2]2[CH:3]=[N:4][N:5]([C:9]3[CH:22]=[CH:21][C:12]([C:13]([NH:15][CH2:16][CH2:17][CH2:18][O:19][CH3:20])=[O:14])=[CH:11][N:10]=3)[C:6]=2[O:7][CH3:8])=[C:24]([F:23])[CH:25]=1)#[N:28]Participants
8
Reactant 3
Product 1
Reagents, catalysts & solvents 4
Procedure
Combined 6-(4-bromo-5-methoxy-1H-pyrazol-1-yl)-N-(3-methoxypropyl)nicotinamide (60 mg, 0.163 mmol), 3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (120 mg, 0.488 mmol), PdCl2(dppf)-CH2Cl2 adduct (19.91 mg, 0.024 mmol) and sodium bicarbonate (68.3 mg, 0.813 mmol) in dioxane (0.6 mL) and water (0.15 mL) and heated at 110° C. for 1 h in the microwave. The reaction mixture was diluted with EtOAc, concentrated onto Celite®, and purified on a 10 g NH silica gel column eluted with 0 to 80% EtOAc in hexanes to give 6-(4-(4-cyano-2-fluorophenyl)-5-methoxy-1H-pyrazol-1-yl)-N-(3-methoxypropyl)nicotinamide as a white solid. MS m/z 410 [M+H]+.
Workup
- concentrationconcentrated onto Celite®
- custompurified on a 10 g NH silica gel column
- washeluted with 0 to 80% EtOAc in hexanes
Sources & evidence
- ORD record
- ord-09e9ebf09ac84558bf7c760c1989a578
- Source dataset
- uspto-grants-2015_05
- Patent number
- US09040522B2
Reaction notes
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