Cesium carbonate → HCID 44546886, compound

HRID 908266Notes

Reaction equation

HRID 908266 reaction equation
Br[C:2]1[CH:3]=[C:4]2[NH:10][C:9]([CH2:11][N:12]3[CH:17]=[CH:16][C:15]4[C:18]([C:21](=[O:31])[C:22]5[C:27]([F:28])=[CH:26][C:25]([F:29])=[CH:24][C:23]=5[F:30])=[CH:19][NH:20][C:14]=4[C:13]3=[O:32])=[N:8][C:5]2=[N:6][CH:7]=1.C(OC([N:40]1[CH:44]=[CH:43][CH:42]=[C:41]1B(O)O)=O)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(#N)C.O>[NH:40]1[CH:44]=[CH:43][CH:42]=[C:41]1[C:2]1[CH:3]=[C:4]2[NH:10][C:9]([CH2:11][N:12]3[CH:17]=[CH:16][C:15]4[C:18]([C:21](=[O:31])[C:22]5[C:23]([F:30])=[CH:24][C:25]([F:29])=[CH:26][C:27]=5[F:28])=[CH:19][NH:20][C:14]=4[C:13]3=[O:32])=[N:8][C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27343211-(tert-Butoxycarbonyl)-2-pyrroleboronic AcidHCID 44548760HCID 44548760, compound

Product 1

HCID 44546886HCID 44546886, compoundYield 8.2%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
135 °C

Procedure

A microwavable vial was charged with 6-[(6-bromo-1H-imidazo[4,5-b]pyridin-2-yl)methyl]-3-(2,4,6-trifluorobenzoyl)-1,6-dihydro-7H-pyrrolo[2,3-c]pyridin-7-one (20 mg, 0.04 mmol), [1-(tert-butoxycarbonyl)-1H-pyrrol-2-yl]boronic acid (12.6 mg, 0.06 mmol), cesium carbonate (39 mg, 0.119 mmol), bis(triphenylphosphine)palladium(II) chloride (2.8 mg, 3.98 umol) and acetonitril/water (0.6/0.2 ml). The vial was sealed, purged by 3 cycles of freeze-pump-thaw. The resultant suspension was heated to 135° C. by microwave irradiation for 15 min. LCMS showed complete consumption of the starting material and formation of the desired product. The reaction mixture was diluted with acetonitrile, and filtered through a 0.45 micron membrane filter and then concentrated to dryness under reduced pressure. The crude reaction mixture was purified by HPLC on Xbridge (C18 5u particle size, 30×75 mm) preparative column eluting with a linear gradient of 15-40% acetonitrile/water (0.01% NH4OH) at 70 ml/min. to give the title compound (1.6 mg, 8%). MS (ESI): m/z 489 (M+H). 1H-NMR (500 MHz, d6-DMSO): δ 11.35 (br. s, 1H), 8.61 (s, 1H), 8.03 (s, 1H), 7.89 (s, 1H), 7.58 (d, 1H), 7.36 (m, 2H), 7.00 (d, 1H), 6.86 (s, 1H), 6.54 (s, 1H), 6.11 (s, 1H), 5.47 (s, 2H),

Workup

  1. customThe vial was sealed
  2. custompurged by 3 cycles of freeze-pump-thaw
  3. customconsumption of the starting material and formation of the desired product
  4. additionThe reaction mixture was diluted with acetonitrile
  5. filtrationfiltered through a 0.45 micron membrane
  6. filtrationfilter
  7. concentrationconcentrated to dryness under reduced pressure
  8. customThe crude reaction mixture
  9. customwas purified by HPLC on Xbridge (C18 5u particle size, 30×75 mm) preparative column
  10. washeluting with a linear gradient of 15-40% acetonitrile/water (0.01% NH4OH) at 70 ml/min.

Sources & evidence

ORD record
ord-50830074d76e42fba0f732adeece2510
Source dataset
uspto-grants-2011_09
Patent number
US08017605B2

Reaction notes

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