Cesium carbonate → HCID 59276173, compound

HRID 2070900Notes

Reaction equation

HRID 2070900 reaction equation
S([N:11]1[C:15]2=[N:16][CH:17]=[C:18]([NH:20][C:21]3[N:37]=[C:24]4[CH:25]=[CH:26][CH:27]=[C:28]([CH2:29][N:30]5[CH2:35][CH2:34][NH:33][C:32](=[O:36])[CH2:31]5)[N:23]4[N:22]=3)[CH:19]=[C:14]2[CH:13]=[CH:12]1)(C1C=CC(C)=CC=1)(=O)=O.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.BrC1C=C2C=CN(S(C3C=CC(C)=CC=3)(=O)=O)C2=NC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(#N)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH:11]1[C:15]2=[N:16][CH:17]=[C:18]([NH:20][C:21]3[N:37]=[C:24]4[CH:25]=[CH:26][CH:27]=[C:28]([CH2:29][N:30]5[CH2:35][CH2:34][NH:33][C:32](=[O:36])[CH2:31]5)[N:23]4[N:22]=3)[CH:19]=[C:14]2[CH:13]=[CH:12]1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 224773531H-Pyrrolo[2,3-B]pyridine, 5-bromo-1-[(4-methylphenyl)sulfonyl]-HCID 68586548HCID 68586548, compound

Product 1

HCID 59276173HCID 59276173, compoundYield 57%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6342AcetonitrileSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

4-((2-(1-Tosyl-1H-pyrrolo[2,3-b]pyridin-5-ylamino)-[1,2,4]triazolo[1,5-a]pyridin-5-yl)methyl)piperazin-2-one. A mixture of tris(dibenzylideneacetone)dipalladium(0) (0.019 g, 0.020 mmol) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (0.023 g, 0.041 mmol) in 1,4-dioxane (1.25 mL) was added to 5-bromo-1-tosyl-1H-pyrrolo[2,3-b]pyridine (0.086 g, 0.244 mmol), 4-((2-amino-[1,2,4]triazolo[1,5-c]pyridin-5-yl)methyl)piperazin-2-one (0.050 g, 0.203 mmol), and cesium carbonate (0.265 g, 0.812 mmol) in a 1 dram vial with a stirbar. Nitrogen was blown in to blow out air. The resulting mixture was sealed, stirred vigorously, and heated at 100° C. for 2 h 20 min. The resulting mixture was diluted with acetonitrile, filtered, and purified using reverse-phase semi-preparatory HPLC (10-70% acetonitrile+0.1% trifluoroacetic acid in water+0.1% trifluoroacetic acid, over 34 min). Fractions containing the desired product were combined and loaded onto a Strata X—C ion exchange column from Phenomenex. The column was washed successively with water, acetonitrile, methanol, and then 5% ammonium hydroxide in methanol. The product came off with the 5% ammonium hydroxide in methanol eluent and was concentrated on a rotary evaporator and dried under high vacuum at 40° C. to give the desired product (0.062 g, 0.116 mmol, 57% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm) 9.91 (s, 1H), 8.59 (s, 1H), 8.48 (s, 1H), 7.97 (d, J=7.81 Hz, 2H), 7.77-7.88 (m, 2H), 7.56-7.64 (m, 1H), 7.49-7.56 (m, 1H), 7.42 (d, J=7.81 Hz, 2H), 7.10 (d, J=7.03 Hz, 1H), 6.82 (d, J=3.90 Hz, 1H), 4.08 (s, 2H), 3.13-3.27 (m, 4H), 2.77 (br s, 2H), 2.34 (s, 3H); MS (ESI) m/z 517.1 [M+1]+.

Workup

  1. customThe resulting mixture was sealed
  2. filtrationfiltered
  3. custompurified
  4. customreverse-phase semi-preparatory HPLC (10-70% acetonitrile+0.1% trifluoroacetic acid in water+0.1% trifluoroacetic acid, over 34 min)
  5. additionFractions containing the desired product
  6. washThe column was washed successively with water, acetonitrile, methanol
  7. concentrationwas concentrated on a rotary evaporator
  8. customdried under high vacuum at 40° C.

Sources & evidence

ORD record
ord-94177316cbad4088a36a935398c5d1c2
Source dataset
uspto-grants-2012_10
Patent number
US08299056B2

Reaction notes

Loading…