Trifluoroacetic acid → 2-(2-(4-(isopropylsulfonyl)phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)-5-(1H-pyrazol-5-yl)isoindolin-1-one

HRID 627793Notes

Reaction equation

HRID 627793 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[N:6]([C:12]1[C:20]3[C:15](=[N:16][CH:17]=[C:18]([C:21]4[CH:26]=[CH:25][C:24]([S:27]([CH:30]([CH3:32])[CH3:31])(=[O:29])=[O:28])=[CH:23][CH:22]=4)[N:19]=3)[N:14](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[CH:13]=1)[CH2:5]2.[NH:52]1[C:56](B(O)O)=[CH:55][CH:54]=[N:53]1.C([O-])([O-])=O.[Na+].[Na+].[SiH](CC)(CC)CC.C(O)(C(F)(F)F)=O>O1CCOCC1>[CH:30]([S:27]([C:24]1[CH:23]=[CH:22][C:21]([C:18]2[N:19]=[C:20]3[C:12]([N:6]4[CH2:5][C:4]5[C:8](=[CH:9][CH:10]=[C:2]([C:54]6[NH:53][N:52]=[CH:56][CH:55]=6)[CH:3]=5)[C:7]4=[O:11])=[CH:13][NH:14][C:15]3=[N:16][CH:17]=2)=[CH:26][CH:25]=1)(=[O:28])=[O:29])([CH3:31])[CH3:32]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 10340Sodium CarbonateHCID 12052TriethylsilaneHCID 112519791H-Pyrazole-5-boronic acidHCID 711436245-Bromo-2-[2-(4-isopropylsulfonylphenyl)-5-trityl-pyrrolo[2,3-b]pyrazin-7-yl]isoindolin-1-one

Product 1

HCID 711435972-(2-(4-(isopropylsulfonyl)phenyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl)-5-(1H-pyrazol-5-yl)isoindolin-1-oneYield 21.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

5-bromo-2-[2-(4-isopropylsulfonylphenyl)-5-trityl-pyrrolo[2,3-b]pyrazin-7-yl]isoindolin-1-one (100 mg, 0.1327 mmol), 1H-pyrazol-5-ylboronic acid (17.81 mg, 0.1592 mmol) and Na2CO3 (200 μL of 2 M aqueous solution, 0.40 mmol) combined in 1,4-dioxane (1.5 mL). Mixture de-gassed (×3 vacuum-N2 cycles). Pd(tBu3P)2 (6.782 mg, 0.01327 mmol) added and mixture de-gassed (×3 cycles) then heated overnight at 60° C. Reaction mixture partitioned between DCM and water. Aqueous phase extracted with DCM. Combined organics dried and concentrated. Residue taken up in DCM (2 mL) and Et3SiH (106.0 μL, 0.6635 mmol) then TFA (0.3 mL) added under N2. Mixture stirred for 48 h then concentrated and residue azeotroped with DCM (×3). Residue purified by hplc to give the title compound (14 mg, 21%); 1H NMR (400 MHz, DMSO) 1.22 (6H, d), 3.50 (1H, sep), 5.58 (2H, s), 6.90 (1H, d), 7.83-7.87 (2H, m), 8.00 (2H, d), 8.05 (1H, d), 8.25 (1H, s), 8.53-8.57 (3H, m), 9.11 (1H, s), 12.33 (1H, vbrs), 13.10 (1H, s); MS (ES+) 499.0.

Workup

  1. customMixture de-gassed (×3 vacuum-N2 cycles)
  2. custommixture de-gassed (×3 cycles)
  3. customReaction mixture
  4. custompartitioned between DCM and water
  5. extractionAqueous phase extracted with DCM
  6. customCombined organics dried
  7. concentrationconcentrated
  8. concentrationthen concentrated
  9. customresidue azeotroped with DCM (×3)
  10. customResidue purified by hplc

Sources & evidence

ORD record
ord-40d60793540b4b5a800d6d2b51f7a5c1
Source dataset
uspto-grants-2016_04
Patent number
US09309250B2

Reaction notes

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