Dimethylformamide → HCID 136377156, compound

HRID 1027226Notes

Reaction equation

HRID 1027226 reaction equation
FC(F)(F)S(O[C:7]1[CH:16]=[CH:15][C:14]2[C:9](=[CH:10][C:11]([OH:35])=[C:12]([C:17]3[N:18]=[N:19][C:20]([N:23]([CH3:34])[CH:24]4[CH2:29][C:28]([CH3:31])([CH3:30])[NH:27][C:26]([CH3:33])([CH3:32])[CH2:25]4)=[CH:21][CH:22]=3)[CH:13]=2)[CH:8]=1)(=O)=O.[CH3:38][N:39](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:35][C:11]1[CH:10]=[C:9]2[C:14]([CH:15]=[CH:16][C:7]([C:38]#[N:39])=[CH:8]2)=[CH:13][C:12]=1[C:17]1[N:18]=[N:19][C:20]([N:23]([CH3:34])[CH:24]2[CH2:25][C:26]([CH3:33])([CH3:32])[NH:27][C:28]([CH3:30])([CH3:31])[CH2:29]2)=[CH:21][CH:22]=1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 136377157HCID 136377157, compound

Product 1

HCID 136377156HCID 136377156, compoundYield 50%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
120 °C

Procedure

A degassed mixture of 7-hydroxy-6-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)naphthalen-2-yl trifluoromethanesulfonate (21 mg, 0.033 mmol), zinc cyanide (5.00 mg, 0.043 mmol) and tetrakis(triphenylphosphine)palladium(0) (1.8 mg, 1.6 μmol) in DMF (0.8 mL) was heated at 120° C. under microwave irradiation for 1 h. The reaction mixture was filtered through celite, washed with EtOAc and concentrated. The residue was loaded on a 1 g SCX column, washed with MeOH, and eluted with 2 M NH3 in MeOH. The product-containing fractions were concentrated. The crude product was purified via HPLC to give the title compound as a light yellow solid (6.9 mg, 50% yield). LCMS Rt=0.55 min [Method Q], MS (M+1)=416.3. 1H NMR (METHANOL-d4) δ 8.26 (s, 1H), 8.16 (d, J=9.6 Hz, 1H), 8.04 (s, 1H), 7.86 (d, J=8.6 Hz, 1H), 7.32 (dd, J=8.6, 1.5 Hz, 1H), 7.27 (s, 1H), 7.22 (d, J=9.6 Hz, 1H), 5.05 (t, J=11.9 Hz, 1H), 2.94 (s, 3H), 1.61 (dd, J=13.1, 3.5 Hz, 2H), 1.49 (t, J=12.4 Hz, 2H), 1.30 (s, 6H), 1.14 (s, 6H).

Workup

  1. filtrationThe reaction mixture was filtered through celite
  2. washwashed with EtOAc
  3. concentrationconcentrated
  4. washwashed with MeOH
  5. washeluted with 2 M NH3 in MeOH
  6. concentrationThe product-containing fractions were concentrated
  7. customThe crude product was purified via HPLC

Sources & evidence

ORD record
ord-fb7e26fd0fc74128830c746d8da707ab
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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