Trifluoroacetic acid → HCID 178501621, compound

HRID 1943413Notes

Reaction equation

HRID 1943413 reaction equation
[NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9]2[CH:10]=[C:11]([N:28]([CH:38]3[CH2:40][CH2:39]3)CC3C=CC(OC)=CC=3)[C:12]3[N:13]([C:15]([C:18]([NH:20][C:21]4[CH:26]=[CH:25][N:24]=[CH:23][C:22]=4F)=[O:19])=[CH:16][N:17]=3)[N:14]=2)[CH2:4][CH2:3]1.CCN(C(C)C)C(C)C.Br[CH2:51][C:52]([O:54][CH3:55])=[O:53].C(O)(C(F)(F)[F:59])=O>C(Cl)Cl>[CH:38]1([NH:28][C:11]2[C:12]3[N:13]([C:15]([C:18](=[O:19])[NH:20][C:21]4[CH:26]=[CH:25][N:24]=[C:23]([F:59])[CH:22]=4)=[CH:16][N:17]=3)[N:14]=[C:9]([NH:8][C@H:5]3[CH2:4][CH2:3][C@H:2]([NH:1][CH2:51][C:52]([O:54][CH3:55])=[O:53])[CH2:7][CH2:6]3)[CH:10]=2)[CH2:40][CH2:39]1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 60984Methyl bromoacetateHCID 81531DiisopropylethylamineHCID 178490952HCID 178490952, compound

Product 1

HCID 178501621HCID 178501621, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of 6-((trans)-4-aminocyclohexylamino)-8-(cyclopropyl(4-methoxybenzyl)amino)-N-(3-fluoropyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide 8B (50.0 mg, 0.092 mmol) and DIEA (0.064 mL, 0.367 mmol) in CH2Cl2 (1 mL) was added methyl 2-bromoacetate (21.07 mg, 0.138 mmol), and the reaction mixture was heated 45° C. in a seal-tube apparatus for 14 hrs. The reaction mixture was concentrated, treated with TFA (0.424 mL, 5.51 mmol) and heated at 65° C. for 1 hr. The reaction mixture was concentrated and diluted with methanol and purified using preparative HPLC (Phenomenex Axia Luna 5 micron 30×100 mm) 30% B (Solvent B=90% MeOH-10% H2O-0.1% TFA) to 100% B in A (Solvent A=10% MeOH-90% H2O-0.1% TFA)) to isolate the title compound, methyl N-(trans-4-((8-(cyclopropylamino)-3-((2-fluoro-4-pyridinyl)carbamoyl)imidazo[1,2-b]pyridazin-6-yl)amino)cyclohexyl)glycinate, as an off-white solid ((23 mg, 0.046 mmol, 50.5% yield). LC/MS (Phenomenex Luna 5 micron C18 4.6×30 mm, 0 to 100 B in 2 min with 1 min hold time, Flow rate=5 mL/min, detection at 254 nm, Solvent A: 10% methanol/90% water/0.1% TFA; Solvent B: 10% water/90% methanol/0.1% TFA). Rt=1.32 (M+H=497.3).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. temperatureheated at 65° C. for 1 hr
  3. concentrationThe reaction mixture was concentrated
  4. additiondiluted with methanol
  5. custompurified

Sources & evidence

ORD record
ord-4e9546d2fbe54f42ada7f16935c47044
Source dataset
uspto-grants-2013_03
Patent number
US08389527B2

Reaction notes

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