1-Methylimidazole → Methyl 4-(1-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)piperidin-3-ylcarbamoyl)benzoate

HRID 1755397Notes

Reaction equation

HRID 1755397 reaction equation
FC(F)(F)C(O)=O.[NH2:8][CH:9]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[CH:16]=[C:17]([NH:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[C:27]([O:33][CH3:34])[N:26]=3)[C:18]3[N:19]([CH:21]=[CH:22][N:23]=3)[N:20]=2)[CH2:10]1.[CH3:35][O:36][C:37]([C:39]1[CH:47]=[CH:46][C:42]([C:43](O)=[O:44])=[CH:41][CH:40]=1)=[O:38].CCN=C=NCCCN(C)C.C(N(CC)CC)C.CN1C=CN=C1>ClCCl>[CH3:32][O:31][C:28]1[CH:29]=[CH:30][C:25]([NH:24][C:17]2[C:18]3[N:19]([CH:21]=[CH:22][N:23]=3)[N:20]=[C:15]([N:11]3[CH2:12][CH2:13][CH2:14][CH:9]([NH:8][C:43]([C:42]4[CH:46]=[CH:47][C:39]([C:37]([O:36][CH3:35])=[O:38])=[CH:40][CH:41]=4)=[O:44])[CH2:10]3)[CH:16]=2)=[N:26][C:27]=1[O:33][CH3:34]

Participants

7

Reactant 5

HCID 13901-MethylimidazoleHCID 8471TriethylamineHCID 15513Monomethyl terephthalateHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 866827406-(3-aminopiperidin-1-yl)-N-(5,6-dimethoxypyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine trifluoroacetate

Product 1

HCID 86682742Methyl 4-(1-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)piperidin-3-ylcarbamoyl)benzoateYield 10%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 6-(3-aminopiperidin-1-yl)-N-(5,6-dimethoxypyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine trifluoroacetate (350 mg, 0.94 mmol), 4-(methoxycarbonyl)benzoic acid (171 mg, 0.94 mmol), EDCI (725 mg, 3.79 mmol), triethylamine (288 mg, 2.84 mmol) and 1-methyl-1H-imidazole (311 mg, 3.79 mmol) in dichloromethane (15 mL) was stirred at room temperature for 16 h. The residue was concentrated in vacuo then purified by prep-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; gradient conditions: 20% acetonitrile/80% water (0.1% TFA, v/v) initially, proceeding to 40% acetonitrile/60% water (0.1% TFA, v/v) in a linear fashion over 9 min) to give methyl 4-(1-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)piperidin-3-ylcarbamoyl)benzoate (50 mg, 10%) as a white solid. LC-MS: 532 [M+1]+, tR=1.58 min.

Workup

  1. concentrationThe residue was concentrated in vacuo
  2. customthen purified by prep-HPLC (Gemini 5u C18 150×21.2 mm
  3. waitgradient conditions: 20% acetonitrile/80% water (0.1% TFA, v/v) initially, proceeding to 40% acetonitrile/60% water (0.1% TFA, v/v) in a linear fashion over 9 min

Sources & evidence

ORD record
ord-cdc0213b2d7b4a0cad0ba0513fd5d63e
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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