Hydrochloric Acid → HCID 136377180, compound

HRID 1027291Notes

Reaction equation

HRID 1027291 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:9]=[N:10][N:11]([CH3:13])[CH:12]=2)[CH:5]=[C:4]([O:14]C)[C:3]=1[C:16]1[N:21]=[N:20][C:19]([N:22]([CH3:33])[CH:23]2[CH2:28][C:27]([CH3:30])([CH3:29])[NH:26][C:25]([CH3:32])([CH3:31])[CH2:24]2)=[CH:18][CH:17]=1.FC1C=CC=C(OC)C=1C1N=NC(N(C)C2CC(C)(C)NC(C)(C)C2)=C(C2C=NN(C)C=2)C=1.B(Br)(Br)Br.Cl>C(Cl)Cl.CO>[F:1][C:2]1[C:3]([C:16]2[N:21]=[N:20][C:19]([N:22]([CH3:33])[CH:23]3[CH2:24][C:25]([CH3:31])([CH3:32])[NH:26][C:27]([CH3:30])([CH3:29])[CH2:28]3)=[CH:18][CH:17]=2)=[C:4]([OH:14])[CH:5]=[C:6]([C:8]2[CH:9]=[N:10][N:11]([CH3:13])[CH:12]=2)[CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 25134Boron tribromideHCID 86710717HCID 86710717, compoundHCID 86710720HCID 86710720, compound

Product 1

HCID 136377180HCID 136377180, compoundYield 15%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 6-(2-fluoro-6-methoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine and 6-(2-fluoro-6-methoxyphenyl)-N-methyl-4-(1-methyl-1H-pyrazol-4-yl)-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (0.03 g, 0.07 mmol, total amount of the 2 regioisomers) was dissolved in CH2Cl2 (0.2 M). A 1 M solution of BBr3 in CH2Cl2 (0.3 mL, 3.5 mmol) was rapidly added. The reaction mixture was stirred for 3 h. MeOH was added to the reaction at 0° C. then the solvent was concentrated under reduced pressure. The crude material was purified via reverse phase preparative HPLC (15 to 45% acetonitrile in water, 5 mM ammonium hydroxide as modifier). The solvent was concentrated in vacuo and the resulting solid was suspended in CH3CN/H2O (4/1 mL). 1 M aqueous HCl (3 equivalents) was added and the volatiles were concentrated in vacuo to afford the hydrochloride salt of 3-fluoro-2-(6-(methyl (2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(1-methyl-1H-pyrazol-4-yl)phenol as a yellow solid (5 mg, 15%). LCMS Rt=0.50 min [Method Q]; [M+H]: 439.4; 1H NMR (400 MHz, DMSO) δ 9.20 (d, J=12.0 Hz, 1H), 8.29 (d, J=12.0 Hz, 1H), 8.23 (s, 1H), 8.04 (d, J=9.5 Hz, 1H), 7.92 (s, 1H), 7.79 (bs, 1H), 7.09 (dd, J=12.0, 1.5 Hz, 1H), 7.04 (s, 1H), 4.92 (bs, 1H), 3.88 (s, 3H), 3.03 (s, 3H), 2.05 (t, J=13.0 Hz, 2H), 1.81 (dd, J=13.0, 3.5 Hz, 2H), 1.53 (s, 6H), 1.49 (s, 6H).

Workup

  1. concentrationthe solvent was concentrated under reduced pressure
  2. customThe crude material was purified via reverse phase preparative HPLC (15 to 45% acetonitrile in water, 5 mM ammonium hydroxide as modifier)
  3. concentrationThe solvent was concentrated in vacuo
  4. concentrationthe volatiles were concentrated in vacuo

Sources & evidence

ORD record
ord-345e2b311e2d474b85dd91c5004b51c2
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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