Trifluoroacetic acid → HCID 67241339, compound

HRID 1028144Notes

Reaction equation

HRID 1028144 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:9]2[S:13][C:12]([N:14]3[CH2:20][CH2:19][CH2:18][NH:17][C:16](=[O:21])[CH2:15]3)=[N:11][C:10]=2[Cl:22])[CH:5]=[C:6]([CH3:8])[CH:7]=1.Cl[C:24]1[N:29]=[C:28]([O:30][CH3:31])[CH:27]=[CH:26][N:25]=1.C(=O)([O-])[O-].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(O)(C(F)(F)F)=O>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:22][C:10]1[N:11]=[C:12]([N:14]2[CH2:20][CH2:19][CH2:18][NH:17][C:16](=[O:21])[CH2:15]2)[S:13][C:9]=1[C:4]1[CH:5]=[C:6]([CH3:8])[CH:7]=[C:2]([NH:1][C:24]2[N:29]=[C:28]([O:30][CH3:31])[CH:27]=[CH:26][N:25]=2)[CH:3]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 11430Potassium CarbonateHCID 5889352-Chloro-4-methoxypyrimidineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 67239791HCID 67239791, compound

Product 1

HCID 67241339HCID 67241339, compoundYield 29.1%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
80 °C

Procedure

A sealed tube was charged with a stir bar, 4-[5-(3-amino-5-methylphenyl)-4-chloro-1,3-thiazol-2-yl]-1,4-diazepan-2-one (45 mg, 0.134 mmol), 2-chloro-4-methoxypyrimidine, (20 mg, 0.138 mmol), potassium carbonate (37 mg, 0.268 mmol), Pd2(dba)3 (13 mg, 0.013 mmol), and dicyclohexyl[2′,4′,6′-tri(propan-2-yl)biphenyl-2-yl]phosphane (X-Phos, 31.8 mg, 0.067 mmol). The tube was evacuated and backfilled with argon three times. Fully degassed t-amyl alcohol (450 μl) was added, the tube was sealed and heated at 80° C. for 16 h with stirring. The reaction mixture was then cooled and filtered through a celite plug, which was rinsed with 10% isopropanol in CHCl3. The eluent was concentrated and purified by preparative HPLC Reverse phase (C-18), eluting with Acetonitrile/Water (30-100%), providing 4-(4-chloro-5-{3-[(4-methoxypyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-1,4-diazepan-2-one (19 mg, 0.032 mmol, 29.1%) as a TFA salt. APCI: [M+H]+ m/z 440.1. 1H NMR (500 MHz, dmso) δ9.65 (s, 1H), 8.19 (d, J=5.7, 1H), 7.90 (s, 1H), 7.66 (s, 1H), 7.50 (s, 1H), 6.98 (s, 1H), 6.29 (d, J=5.7 Hz, 1H), 4.15 (s, 2H), 3.93 (s, 3H), 3.76 (s, 2H), 3.23 (s, 2H), 2.28 (s, 3H), 1.77 (s, 2H). rhSYK activity=+++.

Workup

  1. additionA sealed tube was charged with a stir bar
  2. customThe tube was evacuated
  3. additionFully degassed t-amyl alcohol (450 μl) was added
  4. customthe tube was sealed
  5. temperatureThe reaction mixture was then cooled
  6. filtrationfiltered through a celite plug, which
  7. washwas rinsed with 10% isopropanol in CHCl3
  8. concentrationThe eluent was concentrated
  9. custompurified by preparative HPLC Reverse phase (C-18)
  10. washeluting with Acetonitrile/Water (30-100%)

Sources & evidence

ORD record
ord-659420d3c6024336b82890a48d23f33d
Source dataset
uspto-grants-2014_05
Patent number
US08735417B2

Reaction notes

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