Dimethylformamide → HCID 73336116, compound

HRID 710675Notes

Reaction equation

HRID 710675 reaction equation
[Cl:1][C:2]1[C:3](I)=[N:4][N:5]([CH2:8][C:9]([N:11]2[CH2:16][CH2:15][CH2:14][C:13]3[N:17]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[N:18]=[CH:19][C:12]2=3)=[O:10])[C:6]=1[CH3:7].[CH3:28][N:29](C=O)C>O.CCOC(C)=O.[C-]#N.[C-]#N.[Zn+2].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2].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]>[Cl:1][C:2]1[C:3]([C:28]#[N:29])=[N:4][N:5]([CH2:8][C:9]([N:11]2[CH2:16][CH2:15][CH2:14][C:13]3[N:17]([C:20]4[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[N:18]=[CH:19][C:12]2=3)=[O:10])[C:6]=1[CH3:7]

Participants

8

Reactant 2

HCID 6228DimethylformamideHCID 86711685HCID 86711685, compound

Product 1

HCID 73336116HCID 73336116, compoundYield 72%

Reagents, catalysts & solvents 5

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 2-(4-chloro-5-methyl-3-iodopyrazol-1-yl)-1-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]ethanone (430 mg, 0.86 mmol), Zn(CN)2 (151 mg, 1.3 mmol), dppf (72 mg, 0.14 mmol), and Pd2(dba)3 (79 mg, 0.09 mmol) in DMF (10 mL) and water (0.5 mL) was heated at 90° C. overnight. After cooling to room temperature, the reaction mixture was diluted with EtOAc (30 mL) and washed with water (3×5 mL). The EtOAc layer was dried (Na2SO4), filtered, and concentrated in vacuo. The residue was triturated with 1:1 CH2Cl2/MeOH (3×5 mL) to give the desired product as white powder (250 mg, 72%). 1H NMR (400 MHz, DMSO-d6) δ 8.15 (s, 1H), 7.58 (m, 2H), 7.35 (dd, J=8.7, 8.1 Hz, 2H), 5.58 (s, 2H), 3.80 (m, 2H), 2.84 (t, J=5.4 Hz, 2H), 2.25 (s, 3H), 2.00 (m, 2H); MS: (ES) m/z calculated for C19H17ClF4N5O [M+H]+ 399.1, found 399.1.

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with water (3×5 mL)
  3. dry with materialThe EtOAc layer was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was triturated with 1:1 CH2Cl2/MeOH (3×5 mL)

Sources & evidence

ORD record
ord-a469c10bec934e9295abd3071e20a5a1
Source dataset
uspto-grants-2015_11
Patent number
US09181241B2

Reaction notes

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