Thiophenol → 5-(4-amino-1H-pyrazol-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol

HRID 1027178Notes

Reaction equation

HRID 1027178 reaction equation
C1(S)C=CC=CC=1.[NH2:8][C:9]1[CH:10]=[N:11][N:12]([C:14]2[CH:19]=[CH:18][C:17]([C:20]3[N:25]=[N:24][C:23]([N:26]([CH3:37])[CH:27]4[CH2:32][C:31]([CH3:34])([CH3:33])[NH:30][C:29]([CH3:36])([CH3:35])[CH2:28]4)=[CH:22][CH:21]=3)=[C:16]([O:38]C)[CH:15]=2)[CH:13]=1.C([O-])([O-])=O.[K+].[K+]>CN1C(=O)CCC1>[NH2:8][C:9]1[CH:10]=[N:11][N:12]([C:14]2[CH:19]=[CH:18][C:17]([C:20]3[N:25]=[N:24][C:23]([N:26]([CH3:37])[CH:27]4[CH2:32][C:31]([CH3:33])([CH3:34])[NH:30][C:29]([CH3:36])([CH3:35])[CH2:28]4)=[CH:22][CH:21]=3)=[C:16]([OH:38])[CH:15]=2)[CH:13]=1

Participants

5

Reactant 3

HCID 7969ThiophenolHCID 11430Potassium CarbonateHCID 867105706-(4-(4-amino-1H-pyrazol-1-yl)-2-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine

Product 1

HCID 1362530055-(4-amino-1H-pyrazol-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
190 °C

Procedure

As described in GENERAL METHOD 3-1, thiophenol (0.02 mL, 0.23 mmol) was added to a microwave vial containing 6-(4-(4-amino-1H-pyrazol-1-yl)-2-methoxyphenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (100 mg, 0.23 mmol) and K2CO3 (31.7 mg, 0.23 mmol) and NMP (2 mL). The microwave vial was evacuated and filled with N2 (2×). The reaction mixture was heated in a microwave reactor at 190° C. for 20 min, then filtered through celite (pre-packed filter funnel) with methanol. The filtrate was acidified to pH 3 using 1 M HCl aqueous solution and then adsorbed onto a methanol conditioned SCX column. The column was washed several times with methanol then eluted with 2 N ammonia in methanol solution. The eluent was collected, concentrated in vacuo, then purified by preparative HPLC under basic conditions to give 5-(4-amino-1H-pyrazol-1-yl)-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol (50 mg, MS: 422.26 [M+H+]; LCMS Rt=0.43 min (LCMS method Q); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.68 (d, J=10.11 Hz, 1H), 7.49 (d, J=8.59 Hz, 1H), 7.43 (s, 1H), 7.29 (s, 1H), 7.18 (dd, J=8.59, 2.53 Hz, 1H), 7.12 (d, J=2.02 Hz, 1H), 6.89 (d, J=9.60 Hz, 1H), 4.77-4.93 (m, 1H), 2.92 (s, 3H), 1.61 (dd, J=12.38, 3.28 Hz, 2H), 1.33 (t, J=12.38 Hz, 2H), 1.27 (s, 6H), 1.10 (s, 6H).

Workup

  1. additionwas added to a microwave vial
  2. customThe microwave vial was evacuated
  3. additionfilled with N2 (2×)
  4. filtrationfiltered through celite (pre-packed filter funnel) with methanol
  5. washThe column was washed several times with methanol
  6. washthen eluted with 2 N ammonia in methanol solution
  7. customThe eluent was collected
  8. concentrationconcentrated in vacuo
  9. custompurified by preparative HPLC under basic conditions

Sources & evidence

ORD record
ord-869565e584634265a7c14279e448d873
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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