Methyl isonipecotate → HCID 66920876, compound
Reaction equation
[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([O:10][CH2:11][CH3:12])[N:5]=[C:4]([C:13]([NH:15][CH2:16][C:17]2[CH:18]=[N:19][C:20](Cl)=[CH:21][CH:22]=2)=[O:14])[CH:3]=1.[CH3:24][O:25][C:26]([CH:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1)=[O:27]>>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([O:10][CH2:11][CH3:12])[N:5]=[C:4]([C:13]([NH:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([N:31]3[CH2:32][CH2:33][CH:28]([C:26]([O:25][CH3:24])=[O:27])[CH2:29][CH2:30]3)=[N:19][CH:18]=2)=[O:14])[CH:3]=1Participants
Procedure
A mixture of Example 185 (50 mg, 0.15 mmol) and piperidine-4-carboxylic acid methyl ester (0.75 mL) were heated to 140° C. for 20 min. in a microwave reactor. The reaction mixture was extracted with ethyl acetate (5 mL) and washed with 1M HCl (2×10 mL). The organic layer was concentrated in vacuo and purified by silica gel chromatography (50-100% ethyl acetate in hexanes) providing the title compound as an off white solid (34 mg, 52%). 1H NMR (300 MHz, DMSO-d6) δ 8.92 (t, J=6.44 Hz, 1H), 8.05 (d, J=2.03 Hz, 1H), 7.47 (dd, J=8.82, 2.37 Hz, 1H), 7.30 (s, 2H), 7.06 (s, 1H), 6.80 (d, J=8.48 Hz, 1H), 4.48 (q, J=7.12 Hz, 2H), 4.31 (d, J=6.10 Hz, 2H), 4.14 (d, J=13.22 Hz, 2H), 3.60 (s, 3H), 2.82-2.98 (m, 2H), 2.56-2.67 (m, 1H), 1.85 (dd, J=13.56, 3.39 Hz, 2H), 1.43-1.62 (m, 2H), and 1.30 (t, J=7.12 Hz, 3H); MS (ESI) m/e positive ion 461 [M+Na]+, 439 [M+H]+; negative ion 437 [M−H]−.
Workup
- extractionThe reaction mixture was extracted with ethyl acetate (5 mL)
- washwashed with 1M HCl (2×10 mL)
- concentrationThe organic layer was concentrated in vacuo
- custompurified by silica gel chromatography (50-100% ethyl acetate in hexanes)
Sources & evidence
- ORD record
- ord-4c3bdaf14f9a4394a1c4c98c7ab5bf5c
- Source dataset
- uspto-grants-2011_02
- Patent number
- US07888374B2
Reaction notes
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