Diisopropylethylamine → HCID 90033890, compound

HRID 1486829Notes

Reaction equation

HRID 1486829 reaction equation
[C:1]([C:3]1[C:15]2[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([C:16]4[CH:21]=[CH:20][C:19]([N:22]5[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]5)=[CH:18][CH:17]=4)[CH:13]=3)[NH:8][C:7]=2[N:6]=[CH:5][CH:4]=1)#[CH:2].[N:29]([CH2:32][C:33]1[CH:38]=[CH:37][C:36]([CH3:39])=[CH:35][CH:34]=1)=[N+:30]=[N-:31].C(N(C(C)C)CC)(C)C>CN(C=O)C.[Cu]I>[CH3:39][C:36]1[CH:35]=[CH:34][C:33]([CH2:32][N:29]2[CH:2]=[C:1]([C:3]3[C:15]4[C:14]5[C:9](=[CH:10][CH:11]=[C:12]([C:16]6[CH:17]=[CH:18][C:19]([N:22]7[CH2:23][CH2:24][N:25]([CH3:28])[CH2:26][CH2:27]7)=[CH:20][CH:21]=6)[CH:13]=5)[NH:8][C:7]=4[N:6]=[CH:5][CH:4]=3)[N:31]=[N:30]2)=[CH:38][CH:37]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 126217651-(Azidomethyl)-4-methylbenzeneHCID 72195058HCID 72195058, compound

Product 1

HCID 90033890HCID 90033890, compoundYield 66%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-ethynyl-6-(4-(4-methylpiperazin-1-yl)phenyl)-9H-pyrido[2,3-b]indole (example 44, 26.1 mg, 0.071 mmol) in 1.4 mL of anhydrous DMF (C=0.05M), was added CuI (2 mg, 0.15 eq) and 185 μL of a 0.5M solution of 1-(azidomethyl)-4-methylbenzene (1.3 eq). Then, diisopropylethylamine (82 μL, 7 eq) was introduced. The reaction mixture was stirred at room temperature for 15 h. The mixture was then hydrolysed with water (30 mL) The aqueous layer was extracted with AcOEt (4×15 mL). The combined organic layers were washed twice with brine, dried over MgSO4, filtered and concentrated under reduced pressure. A light brown solid was obtained in 66% yield (24.2 mg) after trituration of the crude product in MeOH and filtration. 1H NMR (500 MHz, DMSO) δ 11.99 (s, 1H), 9.01-8.92 (m, 2H), 8.47 (s, 1H), 7.70 (dd, J=8.4, 1.6 Hz, 1H), 7.55 (d, J=8.4 Hz, 1H), 7.49 (d, J=8.7 Hz, 2H), 7.41 (d, J=3.6 Hz, 1H), 7.34 (d, J=7.9 Hz, 2H), 7.19 (d, J=7.8 Hz, 2H), 7.02 (d, J=8.7 Hz, 2H), 5.73 (s, 2H), 3.19 (s, 4H), 2.29 (s, 3H), 2.25 (s, 3H); 13C NMR (126 MHz, DMSO) δ 153.1 (s), 149.5 (s), 145.5 (CH), 144.9 (s), 137.9 (s), 137.3 (s), 132.8 (s), 132.6 (s), 131.6 (s), 131.5 (s), 129.1 (CH), 127.7 (CH), 126.7 (CH), 125.0 (CH), 124.4 (CH), 121.5 (CH), 120.5 (s), 115.5 (CH), 110.9 (CH), 54.4 (2CH2), 52.8 (CH2), 47.9 (2CH2), 45.4 (NCH3), 20.4 (CH3); HRMS calcd for C32H32N7 [M+H]+ 514.2714 found 514.2699.

Workup

  1. extractionhydrolysed with water (30 mL) The aqueous layer was extracted with AcOEt (4×15 mL)
  2. washThe combined organic layers were washed twice with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customA light brown solid was obtained in 66% yield (24.2 mg)
  7. filtrationafter trituration of the crude product in MeOH and filtration

Sources & evidence

ORD record
ord-835bac91bca242159fb8ae9f9cfc31e2
Source dataset
uspto-grants-2016_08
Patent number
US09428500B2

Reaction notes

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