1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)-N-(2-(pyridin-4-yl)ethyl)benzamide

HRID 1755337Notes

Reaction equation

HRID 1755337 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([NH:11][C:12]2[C:13]3[N:14]([CH:27]=[CH:28][N:29]=3)[N:15]=[C:16]([C:18]3[CH:26]=[CH:25][C:21]([C:22]([OH:24])=O)=[CH:20][CH:19]=3)[CH:17]=2)=[N:7][C:8]=1[O:9][CH3:10].[N:30]1[CH:35]=[CH:34][C:33]([CH2:36][CH2:37][NH2:38])=[CH:32][CH:31]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C>CN(C1C=CN=CC=1)C.CN(C=O)C.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([NH:11][C:12]2[C:13]3[N:14]([CH:27]=[CH:28][N:29]=3)[N:15]=[C:16]([C:18]3[CH:19]=[CH:20][C:21]([C:22]([NH:38][CH2:37][CH2:36][C:33]4[CH:34]=[CH:35][N:30]=[CH:31][CH:32]=4)=[O:24])=[CH:25][CH:26]=3)[CH:17]=2)=[N:7][C:8]=1[O:9][CH3:10]

Participants

9

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 832754-PyridineethanamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 715258044-(8-(5,6-Dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid

Product 1

HCID 715258054-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)-N-(2-(pyridin-4-yl)ethyl)benzamideYield 72.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid (47 mg, 0.12 mmol), 2-(pyridin-4-yl)ethanamine (16 mg, 0.132 mmol), HATU (50 mg, 0.132 mmol), DIPEA (18 mg, 0.144 mmol), DMAP (18 mg, 0.144 mmol) and EDCI (28 mg, 0.144 mmol) in DMF (3 mL) was stirred at room temperature for 16 h. Ethyl acetate (50 mL) was added then the mixture was washed with water (2×2 mL) and brine (2×2 mL), then dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was washed with ether and filtered to afford 4-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)-N-(2-(pyridin-4-yl)ethyl)benzamide (43 mg, 72%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 9.96 (s, 1H), 8.71 (t, 1H, J=5.4 Hz), 8.53-8.46 (m, 3H), 8.21 (s, 1H), 8.03-7.94 (m, 4 h), 7.67 (s, 1H), 7.42 (d, 1H, J=8.4 Hz), 7.29-7.27 (m, 2H), 7.11 (d, 1H, J=8.4 Hz), 4.01 (s, 3H), 3.78 (s, 3H), 3.60-3.54 (m, 2H), 2.90 (t, 2H, J=7.2 Hz). LC-MS: [M+H]+, 496, tR=1.226 min, HPLC: 98.86% at 214 nm, 98.46% at 254 nm, tR=3.144 min.

Workup

  1. washthe mixture was washed with water (2×2 mL) and brine (2×2 mL)
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated in vacuo
  4. washThe residue was washed with ether
  5. filtrationfiltered

Sources & evidence

ORD record
ord-772416139bc04472ac7d5530c089a029
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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