Diisopropylethylamine → 2-adamantyl 2-(5-cyanopyridin-2-yl)-2,3-dihydro-1H-spiro[isoquinoline-4,4'-piperidine]-1'-carboxylate

HRID 1424601Notes

Reaction equation

[N:1]1([C:16]([O:18][CH:19]2[CH:26]3[CH2:27][CH:22]4[CH2:23][CH:24]([CH2:28][CH:20]2[CH2:21]4)[CH2:25]3)=[O:17])[CH2:6][CH2:5][C:4]2([C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH2:9][NH:8][CH2:7]2)[CH2:3][CH2:2]1.Cl[C:30]1[N:35]=[CH:34][C:33]([C:36]#[N:37])=[CH:32][CH:31]=1.CCN(C(C)C)C(C)C>CN(C=O)C.CCOCC>[C:36]([C:33]1[CH:32]=[CH:31][C:30]([N:8]2[CH2:7][C:4]3([CH2:5][CH2:6][N:1]([C:16]([O:18][CH:19]4[CH:20]5[CH2:28][CH:24]6[CH2:23][CH:22]([CH2:27][CH:26]4[CH2:25]6)[CH2:21]5)=[O:17])[CH2:2][CH2:3]3)[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH2:9]2)=[N:35][CH:34]=1)#[N:37]

Participants

Conditions

Temperature: 150 °C

Procedure

Crude 2-adamantyl 2,3-dihydro-1H-spiro[isoquinoline-4,4′-piperidine]-1′-carboxylate (21 mg, 0.054 mmol), 6-chloro-3-pyridine carbonitrile (11 mg, 1.5 equiv.) and DIEA (20 μL, 2 equiv.) were dissolved in dry DMF (1.5 mL). The mixture was heated in microwave oven for 20 min at 150° C. The mixture was diluted with ether (10 mL), washed with 3% aq HCl (2×4 mL), concentrated and purified by preparative HPLC to afford 2-adamantyl 2-(5-cyanopyridin-2-yl)-2,3-dihydro-1H-spiro[isoquinoline-4,4′-piperidine]-1′-carboxylate (9.5 mg, 37%). LC-MS Method 1 tR=2.48 min, m/z=483; 1H NMR. (CDCl3) δ=8.67 (br s, 1H), 8.50 (d, 1H), 7.76 (m, 1H), 7.41 (dd, 1H), 7.30 (m, 1H), 7.21 (d, 1H), 6.78 (m, 1H), 4.89 (s, 1H), 4.73 (s, 2H), 4.13 (d, 4H), 3.31 (t, 2H).

Workup

washwashed with 3% aq HCl (2×4 mL)
concentrationconcentrated
custompurified by preparative HPLC

Sources & evidence

ORD record: ord-ce216e82f47744ef800ca625de5d7e4c
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08927715B2

Reaction notes

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