Water → N-(4-(4-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)thiazol-2-yl)pyridin-2-yl)acetamide

HRID 2282303Notes

Reaction equation

HRID 2282303 reaction equation
Br[C:2]1[N:3]=[C:4]([C:20]2[CH:25]=[CH:24][N:23]=[C:22]([NH:26][C:27](=[O:29])[CH3:28])[CH:21]=2)[S:5][C:6]=1[C:7]1[N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[CH:9]=[CH:10][N:11]=1.[CH3:30][N:31]1[CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[C:33]([C:45]([F:48])([F:47])[F:46])=[N:32]1.C(=O)([O-])[O-].[Na+].[Na+].O>COCCOC.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH3:30][N:31]1[CH:35]=[C:34]([C:2]2[N:3]=[C:4]([C:20]3[CH:25]=[CH:24][N:23]=[C:22]([NH:26][C:27](=[O:29])[CH3:28])[CH:21]=3)[S:5][C:6]=2[C:7]2[N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[CH:9]=[CH:10][N:11]=2)[C:33]([C:45]([F:48])([F:47])[F:46])=[N:32]1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 467380121-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-(trifluoromethyl)-1H-pyrazoleHCID 58095120N-(4-(4-bromo-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)thiazol-2-yl)pyridin-2-yl)acetamide

Product 1

HCID 66855234N-(4-(4-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)thiazol-2-yl)pyridin-2-yl)acetamide

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

N-(4-(4-bromo-5-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazol-2-yl)thiazol-2-yl)pyridin-2-yl)acetamide (70.0 mg, 0.120 mmol), 1-methyl-3-trifluoromethyl-1H-pyrazole-4-boronic acid pinacol ester (0.0708 g, 0.241 mmol), [1,1′-bis(diphenylphosphino)ferrocene] palladium(II) dichloride (4.95 mg, 0.00602 mmol) and sodium carbonate (38.3 mg, 0.361 mmol) in DME (1.2 mL) was degassed with argon. Water (0.5 mL) was added to the above mixture. The mixture was irradiated in microwave at 125° C. for 30 min. At that time, LCMS showed the desired product. Reaction mixture was filtered, the filtrate was evaporated to dryness, dissolved in DCM (1.20 mL) and treated with TFA (1.20 mL). This mixture was stirred at room temperature overnight. At that time, LCMS indicated formation of the desired product. The mixture was evaporated to dryness in vacuo, the residue was taken up by DMSO and purified using preparative HPLC to give product as yellow powder (16.3 mg, 31.2%). LCMS: (AA) ES+, 434, 435. 1H NMR (400 MHz, d4-methanol) δ: 8.67 (br, 1H) 8.38 (dd, 1H) 7.87 (s, 1H) 7.63 (dd, 1H) 7.14 (d, 2H) 3.98 (s, 3H) 2.19 (s 3H).

Workup

  1. customThe mixture was irradiated in microwave at 125° C. for 30 min

Sources & evidence

ORD record
ord-324e447d388a4fbcbbf81424745a6c2b
Source dataset
uspto-grants-2015_09
Patent number
US09139589B2

Reaction notes

Loading…