Sodium hydride → HCID 58486384, compound

HRID 1466337Notes

Reaction equation

HRID 1466337 reaction equation
[H-].[Na+].[I-].C[S+](C)(C)=O.F[C:10](F)(F)C(O)=O.[CH3:16][N:17]([CH2:19][C:20]1[CH:49]=[CH:48][C:23]([CH:24]=[CH:25][C:26]2[C:34]3[C:29](=[CH:30][C:31](/[CH:35]=[C:36]4/[C:37](=[O:47])[NH:38][C:39]5[C:44]/4=[CH:43][C:42]([O:45][CH3:46])=[CH:41][CH:40]=5)=[CH:32][CH:33]=3)[NH:28][N:27]=2)=[CH:22][CH:21]=1)[CH3:18]>CN(C=O)C>[CH3:16][N:17]([CH2:19][C:20]1[CH:49]=[CH:48][C:23](/[CH:24]=[CH:25]/[C:26]2[C:34]3[C:29](=[CH:30][C:31]([C@H:35]4[C@@:36]5([C:44]6[C:39](=[CH:40][CH:41]=[C:42]([O:45][CH3:46])[CH:43]=6)[NH:38][C:37]5=[O:47])[CH2:10]4)=[CH:32][CH:33]=3)[NH:28][N:27]=2)=[CH:22][CH:21]=1)[CH3:18]

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 74498Sulfoxonium, trimethyl-, iodide (1:1)2×HCID 178487095HCID 178487095, compound

Product 1

HCID 58486384HCID 58486384, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A, DMF (3 mL) was added to a mixture of NaH (60%, 85.2 mg, 2.1 mmol) and trimethylsulfoxonium iodide (131.5 mg, 0.60 mmol). The resulting mixture was stirred at rt for 10 min followed by the addition of (E)-3-((3-(4-((dimethylamino)methyl)-styryl)-1H-indazol-6-yl)methylene)-5-methoxyindolin-2-one 2,2,2-trifluoroacetate (163 mg, 0.29 mmol) as a solution in DMF (6 mL, divided for transfer and vial rinse). The reaction mixture was not complete after stirring at rt for 24 h. The mixture was heated at 55° C. for 1 h but was still not complete. After cooling to rt, NaH (60%, 44 mg, 1.1 mmol) and trimethylsulfoxonium iodide (69.5 mg, 0.31 mmol) was added and the mixture was heated at 55° C. for 1 h prior to quenching by addition of water (25 mL) and brine (25 mL). The mixture was extracted with EtOAc (300 mL) and the organic layer was washed with brine (2×25 mL), dried over Na2SO4 and concentrated in vacuo. The crude product was purified by silica gel chromatography (5-7.5% 2M NH3-MeOH in DCM) to yield the title compound as a yellow solid (42.8 mg, 32%). 1H NMR (400 MHz, DMSO-d6) δ ppm 13.11 (s, 1H), 10.43 (s, 1H), 8.07 (d, J=8.8 Hz, 1H), 7.64 (d, J=7.6 Hz, 2H), 7.47 (m, 3H), 7.29 (d, J=8.0 Hz, 2H), 7.03 (d, J=8.8 Hz, 1H), 6.74 (d, J=8.4 Hz, 1H), 6.57 (dd, J=8.4, 2.4 Hz, 1H), 5.65 (d, J=2.4 Hz, 1H), 3.38 (s, 2H), 3.28 (s, 3H), 3.20 (t, J=7.6 Hz, 1H), 2.34 (m, 1H), 2.14 (s, 6H), 1.99 (m, 1H); MS ESI [M+H]+ 465.2, calcd for [C29H28N4O2+H]+ 465.2.

Workup

  1. stirringafter stirring at rt for 24 h
  2. temperatureThe mixture was heated at 55° C. for 1 h
  3. temperatureAfter cooling to rt
  4. temperaturethe mixture was heated at 55° C. for 1 h
  5. customto quenching by addition of water (25 mL) and brine (25 mL)
  6. extractionThe mixture was extracted with EtOAc (300 mL)
  7. washthe organic layer was washed with brine (2×25 mL)
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by silica gel chromatography (5-7.5% 2M NH3-MeOH in DCM)

Sources & evidence

ORD record
ord-63c23a6f98f34167b3d37250cbdf8640
Source dataset
uspto-grants-2015_04
Patent number
US08999968B2

Reaction notes

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