Hydrochloric Acid → HCID 44125256, compound

HRID 1162476Notes

Reaction equation

HRID 1162476 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[N:12]([CH:14]=[C:15]([NH:17]C(=O)C)[N:16]=3)[N:13]=2)=[CH:4][C:3]=1[NH:21][S:22]([C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1)(=[O:24])=[O:23].[OH-].[Na+].Cl>CO>[NH2:17][C:15]1[N:16]=[C:11]2[CH:10]=[CH:9][C:8]([C:5]3[CH:4]=[C:3]([NH:21][S:22]([C:25]4[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=4)(=[O:23])=[O:24])[C:2]([Cl:1])=[N:7][CH:6]=3)=[N:13][N:12]2[CH:14]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 44124863N-(6-(6-chloro-5-(4-fluorophenylsulfonamido)pyridin-3-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide

Product 1

HCID 44125256HCID 44125256, compoundYield 14.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A 100 mL, round-bottomed flask was charged with N-(6-(6-chloro-5-(4-fluorophenylsulfonamido)pyridin-3-yl)imidazo[1,2-b]pyridazin-2-yl)acetamide (150 mg, Example 12) and methanol (10 mL)-NaOH (10 N, 5 mL). The mixture was refluxed for 2 h. After the solution was cooled to 0° C., 10 N HCl was added until pH=7. The crude product was concentrated in vacuo. Purification by silica gel chromatography (10 to 50% MeOH/CH2Cl2), followed by further purification by preparative HPLC (Phenomenex Synergi 4μ MAX-RP 150×21.2 mm, 40 to 90% CH3CN/H2O, 0.1% TFA, over 15 min) (Phenomenex, Torrance, Calif.) provided N-(5-(2-aminoimidazo[1,2-b]pyridazin-6-yl)-2-chloropyridin-3-yl)-4-fluorobenzenesulfonamide (20 mg, 5.0% yield) as a yellow solid. MS (ESI positive ion) m/z: 419 (M+1). 1H NMR (400 MHz, DMSO-d6): δ ppm 7.28 (t, J=8.80 Hz, 1H), 7.22-7.31 (m, 1H), 7.49 (s, 1H), 7.55 (d, J=9.19 Hz, 1H), 7.70-7.77 (m, 1H), 7.82-7.90 (m, 2H), 8.52 (d, J=2.15 Hz, 1H), 8.72 (d, J=2.15 Hz, 1H).

Workup

  1. temperatureThe mixture was refluxed for 2 h
  2. concentrationThe crude product was concentrated in vacuo
  3. customPurification by silica gel chromatography (10 to 50% MeOH/CH2Cl2)
  4. customfollowed by further purification by preparative HPLC (Phenomenex Synergi 4μ MAX-RP 150×21.2 mm, 40 to 90% CH3CN/H2O, 0.1% TFA, over 15 min) (Phenomenex, Torrance, Calif.)

Sources & evidence

ORD record
ord-4680a1f1aa864d07aaa5bfd375a7f40b
Source dataset
uspto-grants-2010_10
Patent number
US07820665B2

Reaction notes

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