4-Methylmorpholine → (E)-1-{4-[2-(1H-indazol-3-yl)vinyl]benzoyl}-4-aminopiperidine

HRID 2075447Notes

Reaction equation

[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](/[CH:10]=[CH:11]/[C:12]2[CH:20]=[CH:19][C:15]([C:16]([OH:18])=O)=[CH:14][CH:13]=2)=[N:2]1.C(OC([NH:28][CH:29]1[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]1)=O)(C)(C)C.O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.CN1CCOCC1.Cl.CO>CO>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3](/[CH:10]=[CH:11]/[C:12]2[CH:13]=[CH:14][C:15]([C:16]([N:32]3[CH2:33][CH2:34][CH:29]([NH2:28])[CH2:30][CH2:31]3)=[O:18])=[CH:19][CH:20]=2)=[N:2]1

Participants

Conditions

Temperature: 60 °C

Procedure

The product obtained using (E)-4-[2-(1H-indazol-3-yl)vinyl]benzoic acid (500 mg, 1.89 mmol) obtained in Step 6 of Example 1, 4-(tert-butoxycarbonylamino)piperidine (538 mg, 2.84 mmol), 1-hydroxybenzotriazole monohydrate (332 mg, 2.46 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (510 mg, 2.67 mmol) and N-methylmorpholine (0.420 mL, 3.82 mmol) in a similar manner to Example 5, was dissolved in methanol (10.0 mL), and the solution was added with 4 mol/L hydrogen chloride-methanol solution (5.0 mL), followed by heating under reflux at 60° C. for 90 minutes. The reaction mixture was concentrated under reduced pressure, the residue was extracted after adding with a saturated aqueous potassium carbonate solution and ethyl acetate. The crude product was crystallized from ethyl acetate to obtain Compound 64 (435 mg, 66%).

Workup

customThe product obtained
temperatureby heating
concentrationThe reaction mixture was concentrated under reduced pressure
extractionthe residue was extracted
additionafter adding with a saturated aqueous potassium carbonate solution and ethyl acetate
customThe crude product was crystallized from ethyl acetate

Sources & evidence

ORD record: ord-e291210a13ed470b8aa619f9ce2adff2
Source dataset: uspto-grants-2011_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07919517B2

Reaction notes

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