1-(4-Isopropylpiperazin-1-yl)hex-5-yn-1-one → (S)-tert-Butyl (1-(5-(6-(4-isopropylpiperazin-1-yl)-6-oxohex-1-yn-1-yl)-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl)carbamate

HRID 1052500Notes

Reaction equation

HRID 1052500 reaction equation
Br[C:2]1[CH:3]=[CH:4][N:5]2[C:10]=1[C:9](=[O:11])[N:8]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:7]([C@@H:18]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH3:19])=[N:6]2.[CH:28]([N:31]1[CH2:36][CH2:35][N:34]([C:37](=[O:43])[CH2:38][CH2:39][CH2:40][C:41]#[CH:42])[CH2:33][CH2:32]1)([CH3:30])[CH3:29]>C(NCC)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu](I)I>[CH:28]([N:31]1[CH2:32][CH2:33][N:34]([C:37](=[O:43])[CH2:38][CH2:39][CH2:40][C:41]#[C:42][C:2]2[CH:3]=[CH:4][N:5]3[C:10]=2[C:9](=[O:11])[N:8]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:7]([C@@H:18]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:24])[CH3:25])[CH3:19])=[N:6]3)[CH2:35][CH2:36]1)([CH3:30])[CH3:29]

Participants

6

Reactant 2

HCID 665455341-(4-Isopropylpiperazin-1-yl)hex-5-yn-1-oneHCID 131736124(S)-tert-Butyl (1-(5-bromo-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl)carbamate

Product 1

HCID 131736173(S)-tert-Butyl (1-(5-(6-(4-isopropylpiperazin-1-yl)-6-oxohex-1-yn-1-yl)-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl)carbamateYield 72.9%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8021DiethylamineSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of (S)-tert-butyl (1-(5-bromo-4-oxo-3-phenyl-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl)carbamate (140 mg, 0.32 mmol), 1-(4-isopropylpiperazin-1-yl)hex-5-yn-1-one (88 mg, 0.36 mmol), bis(triphenylphosphine)palladium(II) chloride (23 mg, 0.03 mmol) and copper iodide (6 mg, 0.03 mmol) in diethylamine (6 ml) was heated at 60° C. for 3 days. The solvent was removed and the crude purified by reverse phase chromatography (C-18 silica from Waters®, water/1:1 acetonitrile-methanol as eluents [0.1% v/v formic acid buffered] 0% to 100%) to give 134 mg (72% yield) of the title compound. Purity 100%.

Workup

  1. customThe solvent was removed
  2. customthe crude purified by reverse phase chromatography (C-18 silica from Waters®, water/1:1 acetonitrile-methanol as eluents [0.1% v/v formic acid

Sources & evidence

ORD record
ord-9a5eaa5bbf5a443e9aef2cb23dff011c
Source dataset
uspto-grants-2016_07
Patent number
US09388189B2

Reaction notes

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