5-Methylindolin-2-one → HCID 178422516, compound

HRID 1615342Notes

Reaction equation

HRID 1615342 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[CH2:5]2.[CH3:12][N:13]([CH3:41])[CH2:14][CH2:15][N:16]([CH3:40])[C:17](=[O:39])/[CH:18]=[CH:19]/[C:20]1[C:28]2[C:23](=[CH:24][C:25]([CH:29]=O)=[CH:26][CH:27]=2)[N:22](COCC[Si](C)(C)C)[N:21]=1>>[CH3:41][N:13]([CH3:12])[CH2:14][CH2:15][N:16]([CH3:40])[C:17](=[O:39])[CH:18]=[CH:19][C:20]1[C:28]2[C:23](=[CH:24][C:25](/[CH:29]=[C:5]3/[C:6](=[O:11])[NH:7][C:8]4[C:4]/3=[CH:3][C:2]([CH3:1])=[CH:10][CH:9]=4)=[CH:26][CH:27]=2)[NH:22][N:21]=1

Participants

3

Reactant 2

HCID 53257165-Methylindolin-2-oneHCID 86651985HCID 86651985, compound

Product 1

HCID 178422516HCID 178422516, compound

Procedure

The title compound was synthesized according to the method described in Example A57 from 5-methylindolin-2-one (8.0 mg, 0.0535 mmol) and (E)-N-(2-(dimethylamino)ethyl)-3-(6-formyl-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-3-yl)-N-methylacrylamide (23 mg, 0.0535 mmol) with a modified purification procedure. The product was extracted into EtOAc after the final deprotection step and washed with NaHCO3(sat) (2×), brine (2×) and the organic layer dried over MgSO4. After removal of solvent the resulting film was titurated with Et2O/hexanes to give after drying 9.4 mg, 41% yield of a yellow solid which was a 77:23 mixture of (E)/(Z) isomers. 1H NMR (400 MHz, CD3OD) δ 8.94, 7.91 (s, 1H), 8.20, 8.16 (d, J=8.7 Hz, 1H), 7.98-7.93 (m, 1H), 7.84 (s, 1H), 7.59, 7.43 (d, J=8.2 Hz, 1H), 7.52-7.42 (m, 2H), 7.08 (d, J=7.2 Hz, 1H), 6.82, 6.78 (d, J=7.6 Hz, 1H), 3.77-3.68 (m, 2H), 3.60, 3.13 (s, 3H), 2.68-2.61 (m, 2H), 2.37 (s, 6H), 2.19 (s, 3H); MS ESI 430.3 [M+H]+, calcd for [C25H27N5O2+H]+ 430.22.

Workup

  1. extractionThe product was extracted into EtOAc after the final deprotection step
  2. washwashed with NaHCO3(sat) (2×), brine (2×)
  3. dry with materialthe organic layer dried over MgSO4
  4. customAfter removal of solvent the resulting film
  5. customto give

Sources & evidence

ORD record
ord-9bf889bcf3494789a4c8d3a08c4fd68a
Source dataset
uspto-grants-2014_07
Patent number
US08765748B2

Reaction notes

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