1-Methylimidazole → (3-(8-(6-(2-Methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)phenyl)(morpholino)methanone

HRID 1755356Notes

Reaction equation

HRID 1755356 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][CH:33](C)[CH2:34][OH:35].CN1[CH:42]=[CH:41]N=C1.CCN=C=NCCCN(C)C>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]([C:23]([N:32]4[CH2:42][CH2:41][O:35][CH2:34][CH2:33]4)=[O:24])[CH:26]=[CH:27][CH:28]=3)[CH:19]=2)[CH:10]=[CH:9][CH:8]=1

Participants

6

Reactant 4

HCID 13901-MethylimidazoleHCID 51262-AminopropanolHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 715255203-(8-(6-(2-Methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid

Product 1

HCID 71525989(3-(8-(6-(2-Methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)phenyl)(morpholino)methanoneYield 51.3%

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 (50 mg, 0.121 mmol), 2-aminopropan-1-ol (12 mg, 0.133 mmol), 1-methyl-1H-imidazole (40 mg, 0.484 mmol) and EDCI (92 mg, 0.484 mmol) in dichloromethane (10 mL) was stirred at room temperature for 20 h then concentrated. The residue was purified by Prep-TLC (silica gel, 200-300 mesh, methanol:dichloromethane=1:30) to afford (3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)phenyl)(morpholino)methanone (30 mg, 51%) as a yellow solid. 1H NMR (300 MHz, CD3OD): δ 8.84 (s, 1H), 8.11-8.01 (m, 3H), 7.61-7.54 (m, 3H), 7.44 (t, 1H, J=8.1 Hz), 6.30 (d, 1H, J=7.8 Hz), 6.09 (d, 1H, J=8.4 Hz), 4.27-4.21 (m, 1H), 3.79-3.44 (m, 10H), 2.18-2.04 (m, 3H), 1.79 (brs, 1H), 1.19 (d, 3H, J=6.3 Hz). LC-MS: [M+H]+, 484, tR=1.738 min, HPLC: 99.76% at 214 nm, 99.56% at 254 nm, tR=5.698 min.

Workup

  1. concentrationthen concentrated
  2. customThe residue was purified by Prep-TLC (silica gel, 200-300 mesh, methanol:dichloromethane=1:30)

Sources & evidence

ORD record
ord-993d4002c53e4c15a6f354d325bef96a
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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