Trifluoroacetic acid → HCID 178474200, compound

HRID 1943494Notes

Reaction equation

HRID 1943494 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:11])[CH3:10])[CH:5]=[CH:6][CH:7]=1.C(OC([NH:19][C@H:20]1[CH2:25][CH2:24][C@H:23]([NH:26][C:27]2[CH:28]=[C:29]([N:39]([CH:49]3[CH2:51][CH2:50]3)CC3C=CC(OC)=CC=3)[C:30]3[N:31]([C:33]([C:36](O)=[O:37])=[CH:34][N:35]=3)[N:32]=2)[CH2:22][CH2:21]1)=O)(C)(C)C.CCN(C(C)C)C(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(O)(C(F)(F)F)=O>CN(C=O)C>[C:9]([NH:8][C:4]1[CH:3]=[C:2]([NH:1][C:36]([C:33]2[N:31]3[N:32]=[C:27]([NH:26][C@H:23]4[CH2:24][CH2:25][C@H:20]([NH2:19])[CH2:21][CH2:22]4)[CH:28]=[C:29]([NH:39][CH:49]4[CH2:51][CH2:50]4)[C:30]3=[N:35][CH:34]=2)=[O:37])[CH:7]=[CH:6][CH:5]=1)(=[O:11])[CH3:10]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 7604m-AminoacetanilideHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 178490957HCID 178490957, compound

Product 1

HCID 178474200HCID 178474200, compoundYield 27.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To N-(3-aminophenyl)acetamide (4.09 mg, 0.027 mmol), 83C (10 mg, 0.018 mmol) and DIEA in DMF (0.5 mL) was added benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (16.06 mg, 0.036 mmol) and the reaction was stirred at room temperature overnight. One mL of TFA was added to the reaction mixture and heated at 60° C. After 1 hr, the reaction mixture was concentrated under reduced pressure and purified using preparative HPLC containing TFA to isolate N-(3-acetamidophenyl)-6-((trans)-4-aminocyclohexylamino)-8-(cyclopropylamino)imidazo[1,2-b]pyridazine-3-carboxamide (4 mg, 5.02 μmol, 27.6% yield) as a white solid. 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=1.3 minutes. [M+H]=463.23. 1H NMR (500 MHz, METHANOL-d3) δ ppm 10.99 (1H, s), 7.92 (1H, d, J=1.83 Hz), 7.62 (1H, d, J=8.25 Hz), 7.37 (2H, t, J=8.25 Hz), 7.16 (1H, d, J=8.25 Hz), 6.08 (1H, s), 3.80 (1H, t, J=4.35 Hz), 3.09-3.26 (1H, m), 2.51-2.72 (1H, m, J=6.76, 6.76, 3.67, 3.44 Hz), 2.35 (2H, d, J=10.08 Hz), 2.11-2.24 (3H, m), 1.98-2.14 (2H, m), 1.67-1.89 (2H, m, J=12.72, 12.43, 12.43, 3.21 Hz), 1.37-1.53 (2H, m), 1.20-1.38 (1H, m), 0.82-1.00 (2H, m), 0.58-0.76 (2H, m).

Workup

  1. temperatureheated at 60° C
  2. waitAfter 1 hr
  3. concentrationthe reaction mixture was concentrated under reduced pressure
  4. custompurified
  5. additioncontaining TFA

Sources & evidence

ORD record
ord-cfd2d0f8362949a0a2c102c360d56667
Source dataset
uspto-grants-2013_03
Patent number
US08389527B2

Reaction notes

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