Water → 2-amino-N,N-diethyl-5-[1-(3-hydroxypropyl)-1H-pyrazol-4-yl]benzamide
Reaction equation
[NH2:1][C:2]1[CH:14]=[CH:13][C:12](Br)=[CH:11][C:3]=1[C:4]([N:6]([CH2:9][CH3:10])[CH2:7][CH3:8])=[O:5].CC1(C)C(C)(C)OB([C:24]2[CH:25]=[N:26][N:27]([CH2:29][CH2:30][CH2:31][OH:32])[CH:28]=2)O1.ClCCl.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1.O>>[NH2:1][C:2]1[CH:14]=[CH:13][C:12]([C:24]2[CH:25]=[N:26][N:27]([CH2:29][CH2:30][CH2:31][OH:32])[CH:28]=2)=[CH:11][C:3]=1[C:4]([N:6]([CH2:9][CH3:10])[CH2:7][CH3:8])=[O:5]Participants
Reactant 6
Product 1
Procedure
A suspension of 2-amino-5-bromo-N,N-diethylbenzamide (Compound 3D, 326 mg, 1.20 mmol), 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propan-1-ol (Compound 3E, 0.33 g, 1.32 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (106.8 mg, 0.13 mmol) and potassium carbonate (0.50 g, 3.64 mmol) in 1,4-dioxane (4 mL, 50 mmol) to H2O (1 mL, 60 mmol) was evacuated and charged with argon (3×). The sample was irradiated in a microwave reactor for 30 min at 100° C. The crude product was concentrated in vacuo to a solid and purified using a Teledyne ISCO Combiflash® Rf system [0→5% MeOH in DCM] to yield the desired product (197 mg, 52%). 1H NMR (400 MHz, CD3OD) δ 7.86 (d, J=0.51 Hz, 1H), 7.71 (d, J=0.76 Hz, 1H), 7.36 (dd, J=2.02, 8.34 Hz, 1H), 7.22 (d, J=2.02 Hz, 1H), 6.81 (d, J=8.34 Hz, 1H), 4.24 (t, J=6.82 Hz, 2H), 3.33-3.60 (m, 6H), 2.05 (quin, J=6.57 Hz, 2H), 1.04-1.35 (m, 6H). MS (ESI): m/z 317.59 [M+H]+. UPLC: tR=0.74 min (UPLC-SQD: analytical—2 min).
Workup
- customwas evacuated
- additioncharged with argon (3×)
- customThe sample was irradiated in a microwave reactor for 30 min at 100° C
- concentrationThe crude product was concentrated in vacuo to a solid
- custompurified
Sources & evidence
- ORD record
- ord-eea831bf2b4d4af7809519c37f94a35b
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09133224B2
Reaction notes
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