Trifluoroacetic acid → HCID 178501624, compound

HRID 1943488Notes

Reaction equation

HRID 1943488 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](CC3C=CC(OC)=CC=3)[C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=3)[C:12]3[N:13]([C:15]([C:18]([NH:20][C:21]4[CH:26]=[CH:25][N:24]=[C:23]([F:27])[CH:22]=4)=[O:19])=[CH:16][N:17]=3)[N:14]=2)[CH2:4][CH2:3]1.CCN(C(C)C)C(C)C.Br[CH2:54][C:55]([O:57][CH3:58])=[O:56].C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:27][C:23]1[CH:22]=[C:21]([NH:20][C:18]([C:15]2[N:13]3[N:14]=[C:9]([NH:8][C@H:5]4[CH2:6][CH2:7][C@H:2]([NH:1][CH2:54][C:55]([O:57][CH3:58])=[O:56])[CH2:3][CH2:4]4)[CH:10]=[C:11]([NH:28][C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=4)[C:12]3=[N:17][CH:16]=2)=[O:19])[CH:26]=[CH:25][N:24]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 60984Methyl bromoacetateHCID 81531DiisopropylethylamineHCID 178490938HCID 178490938, compound

Product 1

HCID 178501624HCID 178501624, compoundYield 34.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of 62B (30.0 mg, 0.052 mmol) in DCM (2 mL) was added DIEA (0.036 mL, 0.206 mmol) and methyl 2-bromoacetate (11.84 mg, 0.077 mmol) and the reaction solution was stirred at 45° C. for 14 h. The solvent was removed under reduced pressure and the residue was treated with TFA (0.238 mL, 3.09 mmol). The reaction mixture was stirred at 65° C. for 1 h, and then concentrated, diluted with MeOH and purified by 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 obtain methyl N-(trans-4-((3-((2-fluoro-4-pyridinyl)carbamoyl)-8-(2-pyridinylamino)imidazo[1,2-b]pyridazin-6-yl)amino)cyclohexyl)glycinate (9.6 mg, 0.018 mmol, 34.9% yield).). HPLC Rt=1.528 minutes (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). [M+H]=534.18.

Workup

  1. customThe solvent was removed under reduced pressure
  2. stirringThe reaction mixture was stirred at 65° C. for 1 h
  3. concentrationconcentrated
  4. additiondiluted with MeOH
  5. custompurified by 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)

Sources & evidence

ORD record
ord-66150e3d52d444b1b5f94fb275f0692d
Source dataset
uspto-grants-2013_03
Patent number
US08389527B2

Reaction notes

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