Sodium hydride → US9907800, Example A12

HRID 447507Notes

Reaction equation

HRID 447507 reaction equation
[I-].[CH3:2][S+](C)(C)=O.[H-].[Na+].[NH:9]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([CH:18]=[C:19]3[C:27]4[C:22](=[N:23][CH:24]=[C:25]([Br:28])[CH:26]=4)[NH:21][C:20]3=[O:29])[CH:16]=2)[CH:11]=[N:10]1>CN(C=O)C>[Br:28][C:25]1[CH:26]=[C:27]2[C@:19]3([CH2:2][C@H:18]3[C:15]3[CH:16]=[C:17]4[C:12]([CH:11]=[N:10][NH:9]4)=[CH:13][CH:14]=3)[C:20](=[O:29])[NH:21][C:22]2=[N:23][CH:24]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 178517361HCID 178517361, compound

Product 1

HCID 58486134US9907800, Example A12

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a mixture of trimethylsulfoxonium iodide (220 mg, 1 mmol) and 60% NaH (120 mg, 3 mmol) in a RBF was added DMF (5 mL). The resulting mixture was stirred for 5 min at rt. A solution of (E & Z)-3-((1H-indazol-6-yl)methylene)-5-bromo-1H-pyrrolo[2,3-b]pyridin-2(3H)-one (170 mg, 0.5 mmol) in DMF (5 mL) was added. After addition, the resulting mixture was heated at 55° C. (oil temp.) for 2.5 h. Upon cooling to 0° C., it was quenched with ice, sat. NH4Cl, extracted with EtOAc (50 mL×2). Combined extracts were dried (Na2SO4) and concentrated to give light brown liquid. The residue was purified by flash chromatography (eluent: CH2Cl2/MeOH/Et3N 100:5:1 to 100:10:1) to give the title compound as a pale yellow oil which was triturated with CH2Cl2. The resulting precipitates were collected by suction filtration and dried to give the title compound (66 mg, 37%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 13.07 (s, 1H), 11.42 (s, 1H), 8.04 (s, 1H), 8.02 (d, J=2.0 Hz, 1H), 7.68 (d, J=8.4 Hz, 1H), 7.51 (s, 1H), 6.98 (d, J=8.0 Hz, 1H), 6.44 (d, J=2.0 Hz, 1H), 2.60 (dd, J=8.0 Hz, J=4.4 Hz, 1H), 2.10 (dd, J=8.8 Hz, J=4.8 Hz, 1H); MS ESI 355.1 [M+H]+, calcd for [C16H11BrN4O+H]+ 355.0.

Workup

  1. additionAfter addition
  2. temperaturethe resulting mixture was heated at 55° C. (oil temp.) for 2.5 h
  3. temperatureUpon cooling to 0° C.
  4. customit was quenched with ice, sat. NH4Cl
  5. extractionextracted with EtOAc (50 mL×2)
  6. dry with materialCombined extracts were dried (Na2SO4)
  7. concentrationconcentrated
  8. customto give light brown liquid
  9. customThe residue was purified by flash chromatography (eluent: CH2Cl2/MeOH/Et3N 100:5:1 to 100:10:1)

Sources & evidence

ORD record
ord-af5998cf3b054190b31e02da631238e2
Source dataset
uspto-grants-2013_07
Patent number
US08481525B2

Reaction notes

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