1-Methylimidazole → Tert-butyl 4-(3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzamido)benzoate

HRID 1755303Notes

Reaction equation

HRID 1755303 reaction equation
[CH3:1][CH:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[N:12]=[C:11]([NH:13][C:14]2[C:15]3[N:16]([CH:29]=[CH:30][N:31]=3)[N:17]=[C:18]([C:20]3[CH:21]=[C:22]([CH:26]=[CH:27][CH:28]=3)[C:23](O)=[O:24])[CH:19]=2)[CH:10]=[CH:9][CH:8]=1.[NH2:32][C:33]1[CH:45]=[CH:44][C:36]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])=[CH:35][CH:34]=1.CCN=C=NCCCN(C)C.CN1C=CN=C1>ClCCl>[CH3:1][CH:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[N:12]=[C:11]([NH:13][C:14]2[C:15]3[N:16]([CH:29]=[CH:30][N:31]=3)[N:17]=[C:18]([C:20]3[CH:21]=[C:22]([CH:26]=[CH:27][CH:28]=3)[C:23]([NH:32][C:33]3[CH:45]=[CH:44][C:36]([C:37]([O:39][C:40]([CH3:41])([CH3:42])[CH3:43])=[O:38])=[CH:35][CH:34]=3)=[O:24])[CH:19]=2)[CH:10]=[CH:9][CH:8]=1

Participants

6

Reactant 4

HCID 13901-MethylimidazoleHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 233272Benzoic acid, 4-amino-, 1,1-dimethylethyl esterHCID 715255203-(8-(6-(2-Methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid

Product 1

HCID 89522698Tert-butyl 4-(3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzamido)benzoateYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-(8-(6-(2-Methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid (49 mg, 0.12 mmol), tert-butyl 4-aminobenzoate (23 mg, 0.12 mmol), EDCI (92 mg, 0.48 mmol), N-methyl-imidazole (40 mg, 0.48 mmol) and dichloromethane (3 mL) was stirred at room temperature for 16 h. The solution was concentrated in vacuo and the residue was purified by chromatography (silica gel, 200-300 mesh, CH2Cl2:MeOH=40:1˜100:1) to give tert-butyl 4-(3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzamido)benzoate (43 mg, 61%) as a yellow oil. [M+H]+, 590.2, tR=2.283 min.

Workup

  1. concentrationThe solution was concentrated in vacuo
  2. customthe residue was purified by chromatography (silica gel, 200-300 mesh, CH2Cl2:MeOH=40:1˜100:1)

Sources & evidence

ORD record
ord-2f2d10b9deee43eaa728614c24cb6877
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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