Dichloromethane → HCID 66799807, compound

HRID 589796Notes

Reaction equation

HRID 589796 reaction equation
Br[C:2]1[CH:3]=[C:4]([S:8]([NH:11][C:12]2[C:13]([OH:21])=[C:14]([CH:18]=[CH:19][CH:20]=2)[C:15]([OH:17])=[O:16])(=[O:10])=[O:9])[S:5][C:6]=1[Cl:7].[F:22][C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][C:24]=1B(O)O.CCN(C(C)C)C(C)C.C(Cl)Cl.C(O)(C(F)(F)F)=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:7][C:6]1[S:5][C:4]([S:8]([NH:11][C:12]2[C:13]([OH:21])=[C:14]([CH:18]=[CH:19][CH:20]=2)[C:15]([OH:17])=[O:16])(=[O:10])=[O:9])=[CH:3][C:2]=1[C:27]1[CH:28]=[C:23]([F:22])[CH:24]=[CH:25][C:26]=1[F:29]

Participants

8

Reactant 5

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 2734335(2,5-Difluorophenyl)boronic acidHCID 66799929HCID 66799929, compound2×

Product 1

HCID 66799807HCID 66799807, compoundYield 44%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of 3-{[(4-bromo-5-chlorothiophen-2-yl)sulfonyl]amino}-2-hydroxybenzoic acid (Intermediate 22) (20.6 mg, 0.050 mmol), 2,5-difluorophenylboronic acid (8.7 mg, 0.055 mmol), DIPEA (35 μL, 0.200 mmol) and Pd(dppf)Cl2.CH2Cl2 (2 mg, 0.003 mmol) in aqueous dioxane (1 mL, 9:1 dioxane/water) was heated at 80° C. under nitrogen atmosphere over night. The reaction mixture was acidified by addition of TFA (50 μL). After being allowed to settle overnight the reaction mixture was filtered, diluted with MeOH and purified by reversed phase chromatography (ACE C8, 5 μm, 21×50 mm, flow 25 ml/min, gradient: 0.1% TFA in water/MeCN over 6 minutes) to give 9.7 mg of the title compound (44%). 1H NMR (500 MHz, MeOH-d4) δ ppm 6.90 (t, J=7.94 Hz, 1 H) 7.14 (dddd, J=8.67, 5.60, 2.93, 0.46 Hz, 1 H) 7.16-7.21 (m, 1 H) 7.20-7.25 (tdd, J=8.96, 4.60, 0.46 Hz, 1 H) 7.34 (d, J=1.59 Hz, 1 H) 7.65 (dd, J=7.94, 1.65 Hz, 1 H) 7.74 (dd, J=7.94, 1.65 Hz, 1 H); MS (ESI+) m/z 446 [M+H]+.

Workup

  1. filtrationthe reaction mixture was filtered
  2. additiondiluted with MeOH
  3. custompurified by reversed phase chromatography (ACE C8, 5 μm, 21×50 mm, flow 25 ml/min, gradient: 0.1% TFA in water/MeCN over 6 minutes)

Sources & evidence

ORD record
ord-aee68583c4104b74a25e10d6ea862418
Source dataset
uspto-grants-2016_01
Patent number
US09233946B2

Reaction notes

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