Dichloromethane → 3-(4-[1-Methyl-5-indolyl]piperazin-1-yl)methyl-1H-pyrrolo[2,3-b]pyridine

HRID 54213Notes

Reaction equation

HRID 54213 reaction equation
FC(F)(F)[C:3](O)=[O:4].C(OC([N:15]1C[CH2:19][N:18]([C:21]2[CH:22]=[C:23]3[C:27](=[CH:28][CH:29]=2)[N:26]([CH3:30])[CH:25]=[CH:24]3)[CH2:17]C1)=O)(C)(C)C.[CH3:31][N:32]([CH2:34][C:35]1[C:43]2[C:38](=[N:39][CH:40]=[CH:41][CH:42]=2)[NH:37][CH:36]=1)[CH3:33].[Cl:44][CH2:45][Cl:46]>>[Cl:44][CH2:45][Cl:46].[CH3:3][OH:4].[NH3:15].[CH3:30][N:26]1[C:27]2[C:23](=[CH:22][C:21]([N:18]3[CH2:19][CH2:31][N:32]([CH2:34][C:35]4[C:43]5[C:38](=[N:39][CH:40]=[CH:41][CH:42]=5)[NH:37][CH:36]=4)[CH2:33][CH2:17]3)=[CH:29][CH:28]=2)[CH:24]=[CH:25]1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 53835493-(Dimethylaminomethyl)-7-azaindoleHCID 199584971-(tert-Butoxycarbonyl)-4-(1-methyl-5-indolyl)piperazine

Product 2

HCID 199584993-(4-[1-Methyl-5-indolyl]piperazin-1-yl)methyl-1H-pyrrolo[2,3-b]pyridineYield 64%HCID 21584172Ammonia methanol dichloromethane

Procedure

Trifluoroacetic acid (5 ml) was added to a solution of 1-(tert-butoxycarbonyl)-4-(1-methyl-5-indolyl)piperazine (0.2102 g, 0.666 mmol) in dichloromethane (5 ml) and the mixture stirred for 30 minutes at room temperature. The mixture was concentrated in vacuo and saturated aqueous potassium carbonate (20 ml) was added to the residue. The mixture was extracted with dichloromethane (2×20 ml), the extracts washed with brine (20 ml), combined and dried (MgSO4). The extracts were concentrated and the residual yellow solid redissolved in toluene (5 ml). 3-Dimethylaminomethyl-1H-pyrrolo[2,3-b]pyridine (0.1136 g, 0.648 mmol) was added and the mixture heated at reflux under nitrogen for 5 hours. The mixture was allowed to cool and the solid present collected. Purification by flash chromatography, eluting with 120:8:1 then 90:8:1 dichloromethane/methanol/ammonia, gave the title compound (0.1433 g, 64%) as a yellow solid. Recrystallisation from methanol afforded pale yellow needles, m.p. 222°-223° C.; (Found: C, 72.81; H, 6.81; N, 20.17. C21H23N5 requires C, 73.02; H, 6.71; N, 20.27%); δH (DMSO-d6) 2.57 (4H, m, 2×piperazinyl CH2), 3.03 (4H, m, 2×piperazinyl CH2), 3.69 (2H, s, CH2N), 3.71 (3H, s, N--CH3), 6.25 (1H, d, J 2.9 Hz, 3'-H), 6.89 (1H, dd, J 8.9, 2.1 Hz, 6'-H), 6.98 (1H, d, J 2.0 Hz, 2-H or 4'-H), 7.05 (1H, dd, J 7.8, 4.6 Hz, 5-H), 7.18 (1H, d, J 2.9 Hz, 2'-H), 7.26 (1H, d, J 8.9 Hz, 7'-H), 7.38 (1H, d, J 2.1 Hz, 4'-H or 2-H), 8.07 (1H, dd, J 7.8, 1.4 Hz, 4-H), 8.20 (1H, dd, J 4.6, 1.4 Hz, 6-H), and 11.46 (1H, br s, NH); m/z (CI+, NH3) 346 (M+1)+.

Workup

  1. concentrationThe mixture was concentrated in vacuo and saturated aqueous potassium carbonate (20 ml)
  2. additionwas added to the residue
  3. extractionThe mixture was extracted with dichloromethane (2×20 ml)
  4. washthe extracts washed with brine (20 ml)
  5. dry with materialdried (MgSO4)
  6. concentrationThe extracts were concentrated
  7. dissolutionthe residual yellow solid redissolved in toluene (5 ml)
  8. temperaturethe mixture heated
  9. temperatureat reflux under nitrogen for 5 hours
  10. temperatureto cool
  11. customPurification by flash chromatography
  12. washeluting with 120:8:1

Sources & evidence

ORD record
ord-849bc9074e694bad9551db0227d46df6
Source dataset
uspto-grants-1997_04
Patent number
US05622950

Reaction notes

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