Trifluoroacetic acid → 1-isopropyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-6-(6-(piperazin-1-yl)pyridin-3-yl)-1H-indole-4-carboxamide

HRID 62310Notes

Reaction equation

HRID 62310 reaction equation
[CH3:1][CH:2]([N:4]1[C:12]2[C:7](=[C:8]([C:32]([NH:34][CH2:35][C:36]3[C:37](=[O:46])[NH:38][C:39]([CH3:45])=[CH:40][C:41]=3[CH2:42][CH2:43][CH3:44])=[O:33])[CH:9]=[C:10]([C:13]3[CH:14]=[CH:15][C:16]([N:19]4[CH2:24][CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21][CH2:20]4)=[N:17][CH:18]=3)[CH:11]=2)[CH:6]=[CH:5]1)[CH3:3].C(O)(C(F)(F)F)=O>ClCCl>[CH:2]([N:4]1[C:12]2[CH:11]=[C:10]([C:13]3[CH:18]=[N:17][C:16]([N:19]4[CH2:20][CH2:21][NH:22][CH2:23][CH2:24]4)=[CH:15][CH:14]=3)[CH:9]=[C:8]([C:32]([NH:34][CH2:35][C:36]3[C:37](=[O:46])[NH:38][C:39]([CH3:45])=[CH:40][C:41]=3[CH2:42][CH2:43][CH3:44])=[O:33])[C:7]=2[CH:6]=[CH:5]1)([CH3:1])[CH3:3]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67467463HCID 67467463, compound

Product 1

HCID 674685761-isopropyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-6-(6-(piperazin-1-yl)pyridin-3-yl)-1H-indole-4-carboxamideYield 86.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 1,1-dimethylethyl 4-{5-[1-(1-methylethyl)-4-({[(6-methyl-2-oxo-4-propyl-1,2-dihydro-3-pyridinyl)methyl]amino}carbonyl)-1H-indol-6-yl]-2-pyridinyl}-1-piperazinecarboxylate (70 mg, 0.112 mmol) in dichloromethane (2 mL) was added TFA (0.5 ml, 6.49 mmol), and the mixture was stirred for 1 h. The mixture was concentrated and the residue was treated with saturated aqueous NaHCO3 solution and filtered. The solid was purified using column chromatography (silica gel, 0 to 15% (9:1 MeOH/NH4OH)/CH2Cl2) to give 1-isopropyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-6-(6-(piperazin-1-yl)pyridin-3-yl)-1H-indole-4-carboxamide (51 mg, 84%) as off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.91 (m, 3H), 1.47 (d, J=4.00 Hz, 6H), 1.53-1.60 (m, 2H), 2.14 (s, 3H), 2.89-2.98 (m, 4H), 3.51-3.59 (m, 4H), 4.40 (d, J=5.05 Hz, 2H), 4.93 (quin, J=6.63 Hz, 1H), 5.92 (s, 1H), 6.87 (d, J=3.03 Hz, 1H), 6.94 (d, J=8.84 Hz, 1H), 7.60 (d, J=3.03 Hz, 1H), 7.66 (d, J=1.26 Hz, 1H), 7.88 (s, 1H), 8.00 (dd, J=8.84, 2.53 Hz, 1H), 8.28 (t, J=5.05 Hz, 1H), 8.58 (d, J=2.27 Hz, 1H). MS: (M+H)+=527.2.

Workup

  1. concentrationThe mixture was concentrated
  2. additionthe residue was treated with saturated aqueous NaHCO3 solution
  3. filtrationfiltered
  4. customThe solid was purified

Sources & evidence

ORD record
ord-139c532148624651ad9456c0881f659a
Source dataset
uspto-grants-2016_09
Patent number
US09446041B2

Reaction notes

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