2-Bromo-1-(cyclopropylmethoxy)-4-(methylsulfonyl)benzene → US10023592, Example 119

HRID 575606Notes

Reaction equation

HRID 575606 reaction equation
[F:1][C:2]1[C:3](=[O:18])[N:4]([CH3:17])[CH:5]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:7]=1.Br[C:20]1[CH:25]=[C:24]([S:26]([CH3:29])(=[O:28])=[O:27])[CH:23]=[CH:22][C:21]=1[O:30][CH2:31][CH:32]1[CH2:34][CH2:33]1>O1CCOCC1.C(=O)(O)[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]>[CH:32]1([CH2:31][O:30][C:21]2[CH:20]=[CH:25][C:24]([S:26]([CH3:29])(=[O:28])=[O:27])=[CH:23][C:22]=2[C:6]2[CH:7]=[C:2]([F:1])[C:3](=[O:18])[N:4]([CH3:17])[CH:5]=2)[CH2:33][CH2:34]1

Participants

6

Reactant 2

HCID 1180216932-Bromo-1-(cyclopropylmethoxy)-4-(methylsulfonyl)benzeneHCID 1238237903-Fluoro-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-one

Product 1

HCID 118022321US10023592, Example 119Yield 46%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 769Bicarbonate IonSolventHCID 312751,4-DioxaneSolvent

Procedure

3-Fluoro-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-one (40 mg, 0.16 mmol), 2-bromo-1-(cyclopropylmethoxy)-4-methanesulfonylbenzene (49 mg, 0.16 mmol), and Pd(dppf)Cl2 (12 mg, 10%) in 1,4-dioxane (880 μL) and saturated bicarbonate solution (aq) (220 μL) were reacted, worked up, and purified in a manner similar to Example 117. The title compound (22 mg, 46%) was obtained as a tan solid. 1H NMR (400 MHz, DMSO-d6) δ 0.31-0.42 (m, 2H) 0.53-0.63 (m, 2H) 1.17-1.34 (m, 1H) 3.20 (s, 3H) 3.58 (s, 3H) 3.95-4.06 (m, 2H) 7.24-7.33 (m, 1H) 7.72-7.79 (m, 1H) 7.80-7.87 (m, 1H) 7.84 (s, 1H) 7.88-7.93 (m, 1H) LCMS (M+H)+=351.

Workup

  1. custompurified in a manner similar to Example 117

Sources & evidence

ORD record
ord-a8b6cb4ef04a4499a6acdcbd05fdacea
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

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