4-Methylmorpholine → (E)-4-[2-(1H-indazol-3-yl)vinyl]-N-(piperidin-4-yl)benzamide dihydrochloride

HRID 2378738Notes

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([N:28]1[CH2:33][CH2:32][CH:31]([NH2:34])[CH2:30][CH2:29]1)=O)(C)(C)C.O.ON1C2C=CC=CC=2N=N1.[ClH:46].C(N=C=NCCCN(C)C)C.CN1CCOCC1.Cl.CO>CO>[ClH:46].[ClH:46].[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]([NH:34][CH:31]3[CH2:32][CH2:33][NH:28][CH2:29][CH2:30]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, 1.66 mmol) obtained in Step 6 of Example 1, 1-tert-butoxycarbonyl-4-aminopiperidine (500 mg, 2.49 mmol), 1-hydroxybenzotriazole monohydrate (291 mg, 2.16 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (450 mg, 2.32 mmol) and N-methylmorpholine (0.37 mL, 3.32 mmol) in a similar manner to Example 5, was dissolved in methanol (2.00 mL), and the solution was added with 4 moL/L hydrogen chloride-methanol solution (1.50 mL), followed by heating under reflux at 60° C. for 30 minutes. The reaction mixture was concentrated under reduced pressure, and the residue was crystallized from acetone to obtain Compound 120 (337 mg, 48%).

Workup

customThe product obtained
temperatureby heating
concentrationThe reaction mixture was concentrated under reduced pressure
customthe residue was crystallized from acetone

Sources & evidence

ORD record: ord-cbd2ee1461a5494995a56611c3eab711
Source dataset: uspto-grants-2008_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07470717B2

Reaction notes

Loading…