Trifluoroacetic acid → HCID 178462174, compound

HRID 1943484Notes

Reaction equation

HRID 1943484 reaction equation
F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.[NH2:28][C@H:29]1[CH2:34][CH2:33][C@H:32]([NH:35][C:36]2[CH:37]=[C:38]([N:55](CC3C=CC(OC)=CC=3)[C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][N:57]=3)[C:39]3[N:40]([C:42]([C:45]([NH:47][C:48]4[CH:53]=[CH:52][N:51]=[C:50]([F:54])[CH:49]=4)=[O:46])=[CH:43][N:44]=3)[N:41]=2)[CH2:31][CH2:30]1.CCN(C(C)C)C(C)C.C(OC([NH:87][C@@H:88]([CH3:92])[C:89](O)=[O:90])=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:87][C@H:88]([C:89]([NH:28][C@H:29]1[CH2:30][CH2:31][C@H:32]([NH:35][C:36]2[CH:37]=[C:38]([NH:55][C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][N:57]=3)[C:39]3[N:40]([C:42]([C:45]([NH:47][C:48]4[CH:53]=[CH:52][N:51]=[C:50]([F:54])[CH:49]=4)=[O:46])=[CH:43][N:44]=3)[N:41]=2)[CH2:33][CH2:34]1)=[O:90])[CH3:92]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531DiisopropylethylamineHCID 85082Tert-butoxycarbonylalanineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 178490938HCID 178490938, compound

Product 1

HCID 178462174HCID 178462174, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

BOP (68.4 mg, 0.155 mmol) was added to a solution of 62B (30.0 mg, 0.052 mmol), DIEA (0.036 mL, 0.206 mmol) and (S)-2-(tert-butoxycarbonylamino)propanoic acid (19.52 mg, 0.103 mmol) in DCM (1 mL). The clear reaction mixture was stirred at room temperature for 30 min, and then concentrated to dryness. TFA (0.238 mL, 3.09 mmol) was added and the reaction solution was stirred at 70° C. for 1 h. The resulting mixture was concentrated and then diluted with MeOH and purified by preparative HPLC (Phenomenex Axia Luna 5 micron 30×100 mm) 10% B (Solvent B=90% MeOH-10% H2O-0.1% TFA) to 90% B in A (Solvent A=10% MeOH-90% H2O-0.1% TFA) to afford 6-((trans-4-(L-alanylamino)cyclohexyl)amino)-N-(2-fluoro-4-pyridinyl)-8-(2-pyridinylamino)imidazo[1,2-b]pyridazine-3-carboxamide (13.7 mg, 0.026 mmol, 49.9% yield) as white solid. HPLC Rt=1.618 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]=533.17.

Workup

  1. concentrationconcentrated to dryness
  2. stirringthe reaction solution was stirred at 70° C. for 1 h
  3. concentrationThe resulting mixture was concentrated
  4. additiondiluted with MeOH
  5. custompurified by preparative HPLC (Phenomenex Axia Luna 5 micron 30×100 mm) 10% B (Solvent B=90% MeOH-10% H2O-0.1% TFA) to 90% B in A (Solvent A=10% MeOH-90% H2O-0.1% TFA)

Sources & evidence

ORD record
ord-17b1d19fddb344b78957e510e92ba430
Source dataset
uspto-grants-2013_03
Patent number
US08389527B2

Reaction notes

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