Dichloromethane → HCID 90313731, compound

HRID 1523910Notes

Reaction equation

HRID 1523910 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]=[C:19]2[CH:25]=[CH:24][NH:23][C:20]2=[N:21][CH:22]=1.Br[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[S:33]([NH:36][CH:37]([CH3:42])[C:38]([F:41])([F:40])[F:39])(=[O:35])=[O:34].C(Cl)Cl.C([O-])(O)=O.[Na+]>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].C(#N)C>[F:1][C:2]1[CH:7]=[C:6]([C:27]2[C:28]([S:33]([NH:36][CH:37]([CH3:42])[C:38]([F:39])([F:40])[F:41])(=[O:34])=[O:35])=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:5]=[CH:4][C:3]=1[C:17]1[N:18]=[C:19]2[CH:25]=[CH:24][NH:23][C:20]2=[N:21][CH:22]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 90313151HCID 90313151, compoundHCID 90313631HCID 90313631, compound

Product 1

HCID 90313731HCID 90313731, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
110 °C

Procedure

To a mixture of 2-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-5H-pyrrolo[2,3-b]pyrazine (32 mg, 0.09 mmol), racemic 2-bromo-N-(1,1,1-trifluoropropan-2-yl)benzenesulfonamide (38 mg, 0.11 mmol) and Pd(dppf)Cl2.CH2Cl2 (6 mg, 0.007 mmol) in a microwave vial were added acetonitrile (2.0 mL) and sat. NaHCO3 (2.0 mL). The mixture was sparged with nitrogen for 5 min and then the vial capped and heated at 110° Celsius for 90 min. After cooling, the reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (25 mL) and brine (25 mL). The organic layer was dried (Na2SO4) and concentrated to dryness. The crude product was purified by HPLC to give the title compound (28 mg, 64%). MS (ESI): mass calcd. C21H16F4N4O2S, 464.09; m/z found, 465.1 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 9.81 (s, 1H), 8.47 (s, 1H), 8.27-8.17 (m, 1H), 7.75-7.41 (m, 5H), 7.40-7.32 (m, 2H), 7.20 (d, J=12.6, 1H), 6.74-6.67 (m, 1H), 4.12-3.94 (m, 1H), 1.39-1.19 (m, 3H).

Workup

  1. customThe mixture was sparged with nitrogen for 5 min
  2. customthe vial capped
  3. temperatureAfter cooling
  4. additionthe reaction mixture was diluted with ethyl acetate (50 mL)
  5. washwashed with water (25 mL) and brine (25 mL)
  6. dry with materialThe organic layer was dried (Na2SO4)
  7. concentrationconcentrated to dryness
  8. customThe crude product was purified by HPLC

Sources & evidence

ORD record
ord-d9a3e4ad0f414892a4585d0a81813d3f
Source dataset
uspto-grants-2015_07
Patent number
US09079866B2

Reaction notes

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