4-Aminopyridine → 8-Bromo-6-chloro-N-(pyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide

HRID 1943397노트

반응식

HRID 1943397 반응식
[Br:1][C:2]1[C:3]2[N:4]([C:9]([C:12]([OH:14])=O)=[CH:10][N:11]=2)[N:5]=[C:6]([Cl:8])[CH:7]=1.ClC1C=C(Cl)C2N(C(C(O)=O)=CN=2)N=1.C(Cl)(=O)C(Cl)=O.C(N(CC)CC)C.[N:42]1[CH:47]=[CH:46][C:45]([NH2:48])=[CH:44][CH:43]=1.ClC1C=C(Cl)C2N(C(C(NC3C=CN=CC=3)=O)=CN=2)N=1>ClCCl.CN(C1C=CN=CC=1)C>[Br:1][C:2]1[C:3]2[N:4]([C:9]([C:12]([NH:48][C:45]3[CH:46]=[CH:47][N:42]=[CH:43][CH:44]=3)=[O:14])=[CH:10][N:11]=2)[N:5]=[C:6]([Cl:8])[CH:7]=1

참가 물질

9

반응물 6

HCID 17274-AminopyridineHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 593138188-Bromo-6-chloroimidazo[1,2-b]pyridazine-3-carboxylic acidHCID 593139086,8-Dichloroimidazo[1,2-b]pyridazine-3-carboxylic acidHCID 596246716,8-Dichloro-N-(pyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide

생성물 1

HCID 596245908-Bromo-6-chloro-N-(pyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide수율 60.8%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매

반응 조건

온도
25 °C

실험 절차

To a 2 dram vial was added a mixture of 8-bromo-6-chloroimidazo[1,2-b]pyridazine-3-carboxylic acid and 6,8-dichloroimidazo[1,2-b]pyridazine-3-carboxylic acid (250 mg, 1.077 mmol), and oxalyl chloride (1.077 mL, 2.155 mmol) in dichloromethane (2 mL). The solution was stirred at 25° C. for 1 hour. The solvent and excess oxalyl chloride were removed in vacuo. The residue was dissolved in dichloromethane (2 mL), and triethylamine (0.451 mL, 3.23 mmol), pyridin-4-amine (152 mg, 1.616 mmol), and 2 crystals of DMAP were added. The reaction solution was stirred at 25° C. for 6 hours. The solution was quenched with dichloromethane, washed 2× with water, dried over anhydrous sodium sulfate, and concentrated in vacuo to give a mixture of 6,8-dichloro-N-(pyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide and 8-bromo-6-chloro-N-(pyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide (202 mg, 0.656 mmol, 60.8% yield). LC/MS, m/z 307.93 (M+1). HPLC Rt, 1.49 min. Waters Sunfire C18 column (4.6×50 mm) 0%-100% B. Solvent B: (90% MeOH, 10% H2O, 0.1% TFA). Solvent A: (10% MeOH, 90% H2O, 0.1% TFA). Gradient, start % B=0, final % B=100, gradient time 4 min, hold at 100% B 1 min, flow rate 4 mL/min.

후처리

  1. additionTo a 2 dram vial was added
  2. customThe solvent and excess oxalyl chloride were removed in vacuo
  3. dissolutionThe residue was dissolved in dichloromethane (2 mL)
  4. stirringThe reaction solution was stirred at 25° C. for 6 hours
  5. customThe solution was quenched with dichloromethane
  6. washwashed 2× with water
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customto give

출처 및 근거

ORD 기록
ord-0515d564b3104f1da39c97d34702118d
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08389527B2

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