N,N-Dimethylformamide--water (1/1) → HCID 58447743, compound

HRID 592204Notes

Reaction equation

HRID 592204 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[CH:12][C:13]([NH:16][C:17](=[O:33])[CH2:18][C:19]3[CH:20]=[C:21](Cl)[C:22]([C:25]4[CH:30]=[CH:29][N:28]=[C:27]([CH3:31])[CH:26]=4)=[N:23][CH:24]=3)=[N:14][CH:15]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[CH3:34][N:35](C=O)C.O>[C-]#N.[Zn+2].[C-]#N.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC(P(C(C)(C)C)[C-]1C=CC=C1)(C)C.C1C=CC([C-]2C(C3C=CC=CC=3)=C(C3C=CC=CC=3)C(C3C=CC=CC=3)=C2C2C=CC=CC=2)=CC=1.[Fe+2]>[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[CH:12][C:13]([NH:16][C:17](=[O:33])[CH2:18][C:19]3[CH:20]=[C:21]([C:34]#[N:35])[C:22]([C:25]4[CH:30]=[CH:29][N:28]=[C:27]([CH3:31])[CH:26]=4)=[N:23][CH:24]=3)=[N:14][CH:15]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

6

Reactant 2

HCID 21962138N,N-Dimethylformamide--water (1/1)HCID 58447928HCID 58447928, compound

Product 1

HCID 58447743HCID 58447743, compound

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 129828017Ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane;iron(2+);(2,3,4,5-tetraphenylcyclopenta-1,4-dien-1-yl)benzeneCatalyst

Conditions

Temperature
130 °C

Procedure

To a sealed tube were added N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-chloro-2′-methyl-2,4′-bipyridin-5-yl)acetamide 184 (46 mg, 0.10 mmol), zinc cyanide (14 mg, 0.12 mmol), Pd2(dba)3 (9 mg, 0.010 mmol), Q-phos (9 mg, 0.022 mmol) and 1 ml DMF/H2O (99/1, v/v). The reaction mixture was bubbled with nitrogen for 1 minute and stirred at 130° C. overnight. After cooling to room temperature, the solvents were evaporated and the crude product was purified by reverse phase HPLC to give N-(5-(4-acetylpiperazin-1-yl)pyridin-2-yl)-2-(3-cyano-2′-methyl-2,4′-bipyridin-5-yl)acetamide 188. MS m/z 456.2 (M+1); 1H NMR 400 MHz (MeOD) δ 8.85(d, 1H), 8.56(d, 1H), 8.28(d, 1H), 7.98(s, 1 Hz), 7.88(d, 1H), 7.78(s, 1H), 7.73-7.70(m, 1 Hz), 7.39(dd, 1H), 3.89(s, 2H), 3.69(t, 2H), 3.65(t, 2H), 3.16(t, 2H), 3.11(t, 2H), 2.61(s, 3H), 2.09(s, 3H).

Workup

  1. customThe reaction mixture was bubbled with nitrogen for 1 minute
  2. temperatureAfter cooling to room temperature
  3. customthe solvents were evaporated
  4. customthe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-ecd3b27393474094ae9c32ad2f860a58
Source dataset
uspto-grants-2016_01
Patent number
US09238646B2

Reaction notes

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