Sodium Carbonate → 2-(4-Isopropylsulfonylphenyl)-5-trityl-pyrrolo[2,3-b]pyrazin-7-amine

HRID 68665Notes

Reaction equation

HRID 68665 reaction equation
Br[C:2]1[N:3]=[C:4]2[C:10]([NH2:11])=[CH:9][N:8]([C:12]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:5]2=[N:6][CH:7]=1.[CH:31]([S:34]([C:37]1[CH:42]=[CH:41][C:40](B(O)O)=[CH:39][CH:38]=1)(=[O:36])=[O:35])([CH3:33])[CH3:32].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1>[CH:31]([S:34]([C:37]1[CH:42]=[CH:41][C:40]([C:2]2[N:3]=[C:4]3[C:10]([NH2:11])=[CH:9][N:8]([C:12]([C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)[C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[C:5]3=[N:6][CH:7]=2)=[CH:39][CH:38]=1)(=[O:35])=[O:36])([CH3:33])[CH3:32]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 441193274-(Isopropylsulphonyl)benzeneboronic acidHCID 866757072-Bromo-5-trityl-pyrrolo[2,3-b]pyrazin-7-amine

Product 1

HCID 711435912-(4-Isopropylsulfonylphenyl)-5-trityl-pyrrolo[2,3-b]pyrazin-7-amine

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
65 °C

Procedure

2-bromo-5-trityl-pyrrolo[2,3-b]pyrazin-7-amine (300 mg, 0.6588 mmol), (4-isopropylsulfonylphenyl)boronic acid (180.3 mg, 0.7906 mmol) and Na2CO3 (988.0 μL of 2 M, 1.976 mmol) combined in dioxane (3 mL) in a microwave tube and the mixture de-gassed (×2 vacuum-N2 cycles). Pd (tBu3P)2 (33.67 mg, 0.06588 mmol) added and the mixture de-gassed (×2 cycles) then heated at 65° C. (block temp), sealing tube with a crimp-top and left to stir for 1 hour. Reaction mixture cooled to ambient temperature and the mixture partitioned between DCM and water. Aqueous phase extracted with DCM and combined organics dried and concentrated. Residue purified by chromatography eluting with 0-30% MeOH-DCM. Brown/yellow solid obtained (332 mg, 90%). 1H NMR (400.0 MHz, DMSO) δ 8.67 (s, 1H), 8.35 (d, J=8.5 Hz, 2H), 7.91 (d, J=8.5 Hz, 2H), 7.35-7.25 (m, 15H), 7.01 (s, 1H), 4.59 (s, 2H), 3.57 (s, 1H), 3.49-3.40 (m, 1H), 1.29 (d, J=12.1 Hz, 2H) and 1.17 (d, J=6.8 Hz, 6H) ppm; MS (ES+) 559.17

Workup

  1. customthe mixture de-gassed (×2 vacuum-N2 cycles)
  2. customthe mixture de-gassed (×2 cycles)
  3. waitleft
  4. customReaction mixture
  5. temperaturecooled to ambient temperature
  6. customthe mixture partitioned between DCM and water
  7. extractionAqueous phase extracted with DCM
  8. customcombined organics dried
  9. concentrationconcentrated
  10. customResidue purified by chromatography
  11. washeluting with 0-30% MeOH-DCM
  12. customBrown/yellow solid obtained (332 mg, 90%)

Sources & evidence

ORD record
ord-2f4c2e92210c4394815b13ab98217571
Source dataset
uspto-grants-2014_09
Patent number
US08822469B2

Reaction notes

Loading…