Trifluoroacetic acid → HCID 135912156, compound

HRID 1798890Notes

Reaction equation

HRID 1798890 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:19]2[CH:23]=[C:22]([C:24]([OH:26])=O)[NH:21][N:20]=2)[CH:5]=[C:6]([Cl:18])[C:7]=1[O:8]CC1C=CC(OC)=CC=1.CCN=C=NCCCN(C)C.Cl.OC1C=CC=C[N+]=1[O-].CN1CCOCC1.[C:54]1([CH:60]([C:64]2[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=2)[CH2:61][CH2:62][NH2:63])[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1.FC(F)(F)C(O)=O>C(Cl)Cl.CO>[Cl:18][C:6]1[CH:5]=[C:4]([C:19]2[CH:23]=[C:22]([C:24]([NH:63][CH2:62][CH2:61][CH:60]([C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)[C:64]3[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=3)=[O:26])[NH:21][N:20]=2)[CH:3]=[C:2]([Cl:1])[C:7]=1[OH:8]

Participants

9

Reactant 6

HCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 796983,3-DiphenylpropylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68632314HCID 68632314, compoundHCID 178526252HCID 178526252, compound

Product 1

HCID 135912156HCID 135912156, compoundYield 32%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of 3-(3,5-dichloro-4-(4-methoxybenzyloxy)phenyl)-1H-pyrazole-5-carboxylic acid (0.05 g, 1.15 mmol) in a mixture of CH2Cl2 (2 mL) and methanol (0.5 mL) under N2 was added N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (0.07 g, 0.35 mmol), 2-hydroxypyridine 1-oxide (0.04 g, 0.35 mmol) and N-methylmorpholine (0.03 mL, 1.15 mmol). The mixture was stirred at room temperature for 30 minutes before addition of 3,3-diphenylpropylamine (48.1 μL, 0.23 mmol). The reaction mixture was then stirred at room temperature for 20 h. The reaction mixture was extracted with water (5 mL) and the organic layer dried via hydrophobic frit washing with CH2Cl2 (2×5 mL). The crude reaction mixture was treated with trifluoroacetic acid (0.5 mL) and stirred at room temperature for 6 h. The solution was concentrated and the residue purified by preparative HPLC to give 0.02 g (32%) of the Compound 3 as a pale brown solid. 1H NMR δ (ppm) (DMSO-d6): 2.30 (2H, q, J=6.80 Hz), 3.16 (2H, q, J=6.80 Hz), 4.03 (1H, t, J=7.59 Hz), 7.15-7.21 (2H, m), 7.26-7.37 (9H, m), 7.78 (2H, s), 8.40 (1H, s), 10.50 (1H, s), 13.50 (1H, s). LCMS (10 cm_ESI_formic_MeOH) tR 4.52 min; m/z 466/468/470 [M+H]+.

Workup

  1. extractionThe reaction mixture was extracted with water (5 mL)
  2. customthe organic layer dried via hydrophobic frit
  3. washwashing with CH2Cl2 (2×5 mL)
  4. customThe crude reaction mixture
  5. stirringstirred at room temperature for 6 h
  6. concentrationThe solution was concentrated
  7. customthe residue purified by preparative HPLC

Sources & evidence

ORD record
ord-0be3f69d8e1f43b69a9e464797eb556b
Source dataset
uspto-grants-2013_01
Patent number
US08343976B2

Reaction notes

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