Dichloromethane → 4'-(5-Aminopyrazin-2-yl)-N-cyclohexyl-3'-fluorobiphenyl-2-sulfonamide

HRID 1523777Notes

Reaction equation

HRID 1523777 reaction equation
[F:1][C:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[CH:4][C:3]=1[C:17]1[N:18]=[CH:19][C:20]([NH2:23])=[N:21][CH:22]=1.Br[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[S:31]([NH:34][CH:35]1[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]1)(=[O:33])=[O:32].C(Cl)Cl.C([O-])([O-])=O.[K+].[K+]>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]>[NH2:23][C:20]1[N:21]=[CH:22][C:17]([C:3]2[CH:4]=[CH:5][C:6]([C:25]3[C:26]([S:31]([NH:34][CH:35]4[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]4)(=[O:33])=[O:32])=[CH:27][CH:28]=[CH:29][CH:30]=3)=[CH:7][C:2]=2[F:1])=[N:18][CH:19]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 33149702-bromo-N-cyclohexylbenzenesulfonamideHCID 903122765-(2-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-phenyl)-pyrazin-2-amine

Product 1

HCID 778448664'-(5-Aminopyrazin-2-yl)-N-cyclohexyl-3'-fluorobiphenyl-2-sulfonamideYield 62.1%

Reagents, catalysts & solvents 1

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

Conditions

Temperature
80 °C

Procedure

To a 5 mL microwave vial were added a stirbar, 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine (54 mg, 0.17 mmol), 2-bromo-N-cyclohexylbenzenesulfonamide (58 mg, 0.18 mmol), Pd(dppf)Cl2.CH2Cl2 (10 mg, 0.013 mmol), and K2CO3 (80 mg, 0.58 mmol). The vial was capped and flushed with nitrogen before adding 1 mL N2 sparged DMSO and heating at 80° Celsius for 20 hours. The vial was cooled to rt and the reaction mixture subjected to FCC purification to give the title compound (45 mg, 62%). MS (ESI): mass calcd. for C22H23FN4O2S, 426.15; m/z found, 427.1 [M+H]+. 1H NMR (500 MHz, DMSO-d6) δ 8.43-8.35 (m, 1H), 8.05-8.03 (d, J=1.4, 1H), 8.03-7.99 (dd, J=7.9, 1.4, 1H), 7.92-7.84 (m, 1H), 7.70-7.64 (m, 1H), 7.64-7.58 (m, 1H), 7.44-7.37 (m, 2H), 7.32-7.24 (m, 2H), 6.72 (s, 2H), 2.85-2.72 (m, 1H), 1.69-1.52 (m, 5H), 1.48-1.39 (m, 1H), 1.19-0.93 (m, 5H).

Workup

  1. customThe vial was capped
  2. customflushed with nitrogen
  3. additionbefore adding 1 mL N2
  4. customsparged DMSO
  5. temperatureThe vial was cooled to rt
  6. customthe reaction mixture subjected to FCC purification

Sources & evidence

ORD record
ord-dbcd16c8219b4d5891af606212351402
Source dataset
uspto-grants-2015_07
Patent number
US09079866B2

Reaction notes

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