5-Amino-1-(2-pyrrolidin-1-ylethyl)indole → 2-(4-Chloro-phenyl)-4-(2-hydroxy-ethyl)-thiazole-5-carboxylic acid [1-(2-pyrrolidin-1-yl-ethyl)-1H-indol-5-yl]-amide

HRID 601519Notes

Reaction equation

HRID 601519 reaction equation
[N:1]1([CH2:6][CH2:7][N:8]2[C:16]3[C:11](=[CH:12][C:13]([NH2:17])=[CH:14][CH:15]=3)[CH:10]=[CH:9]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C[Al](C)C.[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]2[S:30][C:31]3[C:37](=[O:38])[O:36][CH2:35][CH2:34][C:32]=3[N:33]=2)=[CH:25][CH:24]=1>C(Cl)Cl>[N:1]1([CH2:6][CH2:7][N:8]2[C:16]3[C:11](=[CH:12][C:13]([NH:17][C:37]([C:31]4[S:30][C:29]([C:26]5[CH:27]=[CH:28][C:23]([Cl:22])=[CH:24][CH:25]=5)=[N:33][C:32]=4[CH2:34][CH2:35][OH:36])=[O:38])=[CH:14][CH:15]=3)[CH:10]=[CH:9]2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 113905745-Amino-1-(2-pyrrolidin-1-ylethyl)indoleHCID 16682925TrimethylaluminumHCID 574214852-(4-Chloro-phenyl)-6,7-dihydro-pyrano[4,3-d]thiazol-4-one

Product 1

HCID 578702492-(4-Chloro-phenyl)-4-(2-hydroxy-ethyl)-thiazole-5-carboxylic acid [1-(2-pyrrolidin-1-yl-ethyl)-1H-indol-5-yl]-amideYield 79.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Dissolve 1-(2-pyrrolidin-1-yl-ethyl)-1H-indol-5-ylamine (247 mg, 1.08 mmol) in CH2Cl2 (5 mL), cool to 0° C., and treat with a solution of trimethylaluminum (2.0 M in hexanes, 0.7 mL, 1.40 mmol). Stir the solution at 0° C. for 15 min and then at room temperature for 30 min. Add 2-(4-chloro-phenyl)-6,7-dihydro-pyrano[4,3-d]thiazol-4-one (272 mg, 1.02 mmol) neat and stir the reaction at room temperature overnight. Carefully quench the mixture with saturated Rochelles salt solution (5 mL) and stir at room temperature for 1 h. Dilute with additional saturated Rochelles salt solution (10 mL) and extract with CH2Cl2 (3×20 mL). Combine the organic portions, dry, filter, and concentrate under vacuum. Triturate the crude solid with diethyl ether to give the title compound as a white powder (400 mg, 75%). MS (ES+) 495.1 (M+1)+MS (ES−) 493.2 (M−1)−. 1H NMR (400 MHz, DMSO-d6): δ 10.78 (s, 1H), 8.01 (d, 2H, J=8.3 Hz), 7.92 (s, 1H), 7.60 (d, 2H, J=8.8 Hz), 7.46 (d, 1H, J=8.8 Hz), 7.40 (d, 1H, J=3.1 Hz), 7.34 (dd, 1H, J=8.8, 1.8 Hz), 6.41 (d, 1H, J=3.1 Hz), 5.84 (m, 1H), 4.26 (t, 2H, J=6.6 Hz), 3.91 (q, 2H, J=5.3 Hz), 3.21 (t, 2H, J=5.9 Hz), 2.78 (t, 2H, J=6.8 Hz), 2.46 (s, 4H), 1.65 (m, 4H).

Workup

  1. waitat room temperature for 30 min
  2. customthe reaction at room temperature overnight
  3. customCarefully quench the mixture with saturated Rochelles salt solution (5 mL)
  4. stirringstir at room temperature for 1 h
  5. additionDilute with additional saturated Rochelles salt solution (10 mL)
  6. extractionextract with CH2Cl2 (3×20 mL)
  7. customCombine the organic portions, dry
  8. filtrationfilter
  9. concentrationconcentrate under vacuum
  10. customTriturate the crude solid with diethyl ether

Sources & evidence

ORD record
ord-bbdb1645316547e9833a0deb945171c7
Source dataset
uspto-grants-2011_03
Patent number
US07902356B2

Reaction notes

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