Sodium hydride → HCID 25174429, compound

HRID 549449Notes

Reaction equation

HRID 549449 reaction equation
[C:1]([C:3]1[CH:11]=[C:10]2[C:6]([CH2:7][C:8]([CH3:26])([CH3:25])[CH:9]2[NH:12][C:13]([C:15]2[NH:16][C:17]3[C:22]([CH:23]=2)=[CH:21][C:20]([Cl:24])=[CH:19][CH:18]=3)=[O:14])=[CH:5][CH:4]=1)#[N:2].[H-].[Na+].Cl.Cl[CH2:31][CH2:32][N:33]([CH3:35])[CH3:34]>CN(C=O)C.C(Cl)Cl.CCOCC>[Cl:24][C:20]1[CH:21]=[C:22]2[C:17](=[CH:18][CH:19]=1)[N:16]([CH2:31][CH2:32][N:33]([CH3:35])[CH3:34])[C:15]([C:13]([NH:12][C@H:9]1[C:10]3[C:6](=[CH:5][CH:4]=[C:3]([C:1]#[N:2])[CH:11]=3)[CH2:7][C:8]1([CH3:26])[CH3:25])=[O:14])=[CH:23]2

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 11636816N,N-Dimethylaminoethyl chloride hydrochlorideHCID 57573872HCID 57573872, compound

Product 1

HCID 25174429HCID 25174429, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21881112Ethyl ether methylene chlorideSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of N-(6-cyano-2,2-dimethyl-2,3-dihydro-1H-inden-1-yl)-5-chloro-1H-indole-2-carboxamide (30 mg, 0.083 mmol) in DMF (0.3 mL) at rt was added NaH (60% dispersion, 17 mg, 0.42 mmol). After stirring for 15 min, 2-chloro-N,N-dimethylethanamine hydrochloride (36 mg, 0.25 mmol) was added and the resulting mixture was heated at 65° C. for 4 h. After cooling to rt, the reaction mixture was subjected to purification by reverse-phase HPLC using MeOH/water mixtures with 0.1% TFA as the diluent. Fractions containing the major product were collected, combined and concentrated in vacuo to remove the MeOH. The resulting aqueous solution containing the product was made neutral by addition of sat. aq. NaHCO3 and the product was extracted with EtOAc (3×10 mL). The combined extracts were washed with brine, dried over anhyd Na2SO4, filtered and concentrated in vacuo to afford an oil. The oil was redissolved in DCM/Et2O (50/50, 2 mL) and reconcentrated to yield an oil which solidified under vacuum to afford the title compound in the form of a white solid (16 mg). HPLC Ret. time: 2.84 min. LCMS MH+ (m/z) 435.30. 1H NMR: (MeOH-d4, 400 MHz): 7.65 (d, 1H), 7.62-7.60 (m, 2H), 7.51 (d, 1H), 7.42 (d, 1H), 7.30 (dd, 1H), 7.12 (s, 1H), 5.45 (s, 1H), 4.80 (t, 2 H), 3.12 (br m, 2H), 2.93 (m, 2H), 2.59 (s, 6H), 1.32 (s, 3H), 1.07 (s, 3H).

Workup

  1. temperatureAfter cooling to rt
  2. customthe reaction mixture was subjected to purification by reverse-phase
  3. additionFractions containing the major product
  4. customwere collected
  5. concentrationconcentrated in vacuo
  6. customto remove the MeOH
  7. additionThe resulting aqueous solution containing the product
  8. additionwas made neutral by addition of sat. aq. NaHCO3
  9. extractionthe product was extracted with EtOAc (3×10 mL)
  10. washThe combined extracts were washed with brine
  11. dry with materialdried over anhyd Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customto afford an oil
  15. customto yield an oil which

Sources & evidence

ORD record
ord-8b39dbcfaa2c466ca919f4786b53a896
Source dataset
uspto-grants-2011_05
Patent number
US07943658B2

Reaction notes

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