Trifluoroacetic acid → 1-isopropyl-6-(2-piperazin-1-yl-ethoxy)-1H-indole-4-carboxylic acid (6-methyl-2-oxo-4-propyl-1,2-dihydro-pyridin-3-ylmethyl)-amide

HRID 62323Notes

Reaction equation

HRID 62323 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][O:16][C:17]2[CH:25]=[C:24]3[C:20]([CH:21]=[CH:22][N:23]3[CH:26]([CH3:28])[CH3:27])=[C:19]([C:29](=[O:43])[NH:30][CH2:31][C:32]3[C:33](=[O:42])[NH:34][C:35]([CH3:41])=[CH:36][C:37]=3[CH2:38][CH2:39][CH3:40])[CH:18]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>ClCCl>[CH3:41][C:35]1[NH:34][C:33](=[O:42])[C:32]([CH2:31][NH:30][C:29]([C:19]2[C:20]3[CH:21]=[CH:22][N:23]([CH:26]([CH3:27])[CH3:28])[C:24]=3[CH:25]=[C:17]([O:16][CH2:15][CH2:14][N:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]3)[CH:18]=2)=[O:43])=[C:37]([CH2:38][CH2:39][CH3:40])[CH:36]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67465404HCID 67465404, compound

Product 1

HCID 674688131-isopropyl-6-(2-piperazin-1-yl-ethoxy)-1H-indole-4-carboxylic acid (6-methyl-2-oxo-4-propyl-1,2-dihydro-pyridin-3-ylmethyl)-amideYield 20%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 4-(2-{1-isopropyl-4-[(6-methyl-2-oxo-4-propyl-1,2-dihydro-pyridin-3-ylmethyl)-carbamoyl]-1H-indol-6-yloxy}-ethyl)-piperazine-1-carboxylic acid tert-butyl ester (280 mg, 0.472 mmol; prepared following the procedure of Example xx) in dichloromethane (15 mL) was added TFA (1.5 mL) at room temperature and then stirred for 3 h at room temperature. Reaction mixture was concentrated under reduced pressure, diluted with water (20 mL) and washed the resulting aqueous layer with diethyl ether (2×15 mL). The aqueous layer was basified with (pH˜8) with saturated aqueous NaHCO3 solution and extracted with dichloromethane (3×20 mL). The combined organic layer was washed with brine solution (2×25 mL) and concentrated. Purification by preparative HPLC afforded 1-isopropyl-6-(2-piperazin-1-yl-ethoxy)-1H-indole-4-carboxylic acid (6-methyl-2-oxo-4-propyl-1,2-dihydro-pyridin-3-ylmethyl)-amide (48 mg, 20%) as an off white solid. 1H NMR (400 MHz, DMSO-d6): δ 0.93 (t, 3H), 1.42 (d, 6H, J=6.8 Hz), 1.57 (m, 2H), 2.14 (s, 3H), 2.45-2.2 (m, 4H), 2.68 (t, 2H), 2.75 (t, 4H), 4.15-4.19 (m, 2H), 4.35 (d, 2H), 4.78-4.72 (m, 1H), 5.91 (s, 1H), 6.73 (d, 1H), 7.03 (s, 1H), 7.24 (s, 1H), 7.42 (d, 1H), 8.12 (t, 1H), 11.58 (bs, 1H). LCMS (ES+): m/z=494.57[M+H].

Workup

  1. customprepared
  2. customReaction mixture
  3. concentrationwas concentrated under reduced pressure
  4. additiondiluted with water (20 mL)
  5. washwashed the resulting aqueous layer with diethyl ether (2×15 mL)
  6. extractionextracted with dichloromethane (3×20 mL)
  7. washThe combined organic layer was washed with brine solution (2×25 mL)
  8. concentrationconcentrated
  9. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-8c94e203f6e54dcea59cd13fe3987230
Source dataset
uspto-grants-2016_09
Patent number
US09446041B2

Reaction notes

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