1-Methylimidazole → 4-(1-(8-(5,6-Dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-ylcarbamoyl)benzoic acid

HRID 1755408Notes

Reaction equation

HRID 1755408 reaction equation
[NH2:1][CH:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:8]=[C:9]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[C:19]([O:25][CH3:26])[N:18]=3)[C:10]3[N:11]([CH:13]=[CH:14][N:15]=3)[N:12]=2)[CH2:3]1.C[O:28][C:29]([C:31]1[CH:39]=[CH:38][C:34]([C:35](O)=[O:36])=[CH:33][CH:32]=1)=[O:30].CCN=C=NCCCN(C)C.C(N(CC)CC)C.CN1C=CN=C1>ClCCl>[CH3:24][O:23][C:20]1[CH:21]=[CH:22][C:17]([NH:16][C:9]2[C:10]3[N:11]([CH:13]=[CH:14][N:15]=3)[N:12]=[C:7]([N:4]3[CH2:5][CH2:6][CH:2]([NH:1][C:35]([C:34]4[CH:38]=[CH:39][C:31]([C:29]([OH:30])=[O:28])=[CH:32][CH:33]=4)=[O:36])[CH2:3]3)[CH:8]=2)=[N:18][C:19]=1[O:25][CH3:26]

Participants

7

Reactant 5

HCID 13901-MethylimidazoleHCID 8471TriethylamineHCID 15513Monomethyl terephthalateHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 866827496-(3-aminopyrrolidin-1-yl)-N-(5,6-dimethoxypyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine

Product 1

HCID 715265334-(1-(8-(5,6-Dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-ylcarbamoyl)benzoic acidYield 38.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 6-(3-aminopyrrolidin-1-yl)-N-(5,6-dimethoxypyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (180 mg, 0.51 mmol), 4-(methoxycarbonyl)benzoic acid (92 mg, 0.51 mmol), EDCI (389 mg, 2.0 mmol), triethylamine (103 mg, 1.02 mmol) and 1-methyl-1H-imidazole (167 mg, 2.0 mmol) in dichloromethane (10 mL) was stirred at room temperature for 16 h. The residue was concentrated and purified by chromatography (silica gel, 200-300 mesh, dichloromethane:MeOH=20:1) to give 4-(1-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)pyrrolidin-3-ylcarbamoyl)benzoic acid (100 mg, 38%) as a brown liquid. LC-MS: 518 [M+1]+, tR=1.327 min.

Workup

  1. concentrationThe residue was concentrated
  2. custompurified by chromatography (silica gel, 200-300 mesh, dichloromethane:MeOH=20:1)

Sources & evidence

ORD record
ord-93289f5b66f64c43b27486903580bda2
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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