1,1'-Carbonyldiimidazole → N-(6-(2-(3-fluorophenyl)piperidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-3-hydroxyazetidine-1-carboxamide

HRID 588541Notes

Reaction equation

HRID 588541 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]2[CH2:13][CH2:12][CH2:11][CH2:10][N:9]2[C:14]2[CH:15]=[CH:16][C:17]3[N:18]([C:20]([NH2:23])=[CH:21][N:22]=3)[N:19]=2)[CH:5]=[CH:6][CH:7]=1.C1N=CN([C:29]([N:31]2[CH:35]=N[CH:33]=[CH:32]2)=[O:30])C=1.Cl.N1CC([OH:41])C1.CCN(C(C)C)C(C)C>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([CH:8]2[CH2:13][CH2:12][CH2:11][CH2:10][N:9]2[C:14]2[CH:15]=[CH:16][C:17]3[N:18]([C:20]([NH:23][C:29]([N:31]4[CH2:32][CH:33]([OH:41])[CH2:35]4)=[O:30])=[CH:21][N:22]=3)[N:19]=2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 27592903-Hydroxyazetidine hydrochlorideHCID 673077316-(2-(3-Fluorophenyl)piperidin-1-yl)imidazo[1,2-b]pyridazin-3-amine

Product 1

HCID 58334484N-(6-(2-(3-fluorophenyl)piperidin-1-yl)imidazo[1,2-b]pyridazin-3-yl)-3-hydroxyazetidine-1-carboxamideYield 52.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a DCM (2 mL) solution of 6-(2-(3-fluorophenyl)piperidin-1-yl)imidazo[1,2-b]pyridazin-3-amine (45 mg, 0.14 mmol) was added CDI (35 mg, 0.22 mmol) at ambient temperature in one portion. After stirring for five hours, azetidin-3-ol hydrochloride (54 mg, 0.33 mmol) was added in one portion, followed by DIEA (0.05 mL, 0.29 mmol), and the reaction was stirred at ambient temperature overnight. The reaction was diluted with DCM, washed with water, dried over Na2SO4 and concentrated. The crude product was purified by reversed phase column, eluting with 0 to 55% CH3CN/water to obtain the desired product as a solid (30 mg, 51% yield). MS (apci) m/z=411.2 (M+H).

Workup

  1. stirringthe reaction was stirred at ambient temperature overnight
  2. washwashed with water
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe crude product was purified by reversed phase column
  6. washeluting with 0 to 55% CH3CN/water

Sources & evidence

ORD record
ord-f5b62cc92c2449678dfbb60e33225dab
Source dataset
uspto-grants-2016_01
Patent number
US09227975B2

Reaction notes

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