Diisopropylethylamine → (S)-4-Amino-6-((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)amino)pyrimidine-5-carbonitrile

HRID 1052764Notes

Reaction equation

HRID 1052764 reaction equation
[NH2:1][C@H:2]([C:4]1[N:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:8](=[O:16])[C:7]2=[C:17]([C:20]#[C:21][CH2:22][CH2:23][CH2:24][C:25]([N:27]3[CH2:32][CH2:31][N:30]([CH:33]([CH3:35])[CH3:34])[CH2:29][CH2:28]3)=[O:26])[CH:18]=[CH:19][N:6]2[N:5]=1)[CH3:3].[NH2:36][C:37]1[C:42]([C:43]#[N:44])=[C:41](Cl)[N:40]=[CH:39][N:38]=1.CCN(C(C)C)C(C)C>C(O)(C)(C)C>[NH2:36][C:37]1[C:42]([C:43]#[N:44])=[C:41]([NH:1][C@H:2]([C:4]2[N:9]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[C:8](=[O:16])[C:7]3=[C:17]([C:20]#[C:21][CH2:22][CH2:23][CH2:24][C:25]([N:27]4[CH2:32][CH2:31][N:30]([CH:33]([CH3:35])[CH3:34])[CH2:29][CH2:28]4)=[O:26])[CH:18]=[CH:19][N:6]3[N:5]=2)[CH3:3])[N:40]=[CH:39][N:38]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 122782624-Amino-6-chloropyrimidine-5-carbonitrileHCID 118433984(S)-2-(1-Aminoethyl)-5-(6-(4-isopropylpiperazin-1-yl)-6-oxohex-1-yn-1-yl)-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one

Product 1

HCID 118321874(S)-4-Amino-6-((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)amino)pyrimidine-5-carbonitrileYield 25%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of (S)-2-(1-aminoethyl)-5-(6-(4-isopropylpiperazin-1-yl)-6-oxohex-1-yn-1-yl)-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4(3H)-one (120 mg, purity 10%, 0.03 mmol) and 4-amino-6-chloropyrimidine-5-carbonitrile (6 mg, 0.04 mmol) in tert-butanol (3 ml) was added DIEA (44 μl, 0.25 mmol) and the reaction mixture was stirred at 120° C. for 2 days. The solvent was removed under reduced pressure. Ethyl acetate was added and the organic phase was washed with water and brine, dried over magnesium sulphate, filtered and the solvents were removed under reduced pressure. The product was purified by flash chromatography using SP1® Purification System (0% to 100% hexane/AcOEt, 0-8% AcOEt/MeOH) to give 4 mg (25% yield) of the title compound as a white solid. Purity 96%.

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionEthyl acetate was added
  3. washthe organic phase was washed with water and brine
  4. dry with materialdried over magnesium sulphate
  5. filtrationfiltered
  6. customthe solvents were removed under reduced pressure
  7. customThe product was purified by flash chromatography
  8. customSP1® Purification System (0% to 100% hexane/AcOEt, 0-8% AcOEt/MeOH)

Sources & evidence

ORD record
ord-5c0d987d261047bd93fbbd3692402f14
Source dataset
uspto-grants-2016_07
Patent number
US09388189B2

Reaction notes

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