Triethylamine → tert-butyl (3R)-3-{[8-(2-chlorophenyl)-9-(4-chlorophenyl)-9H-purin-6-yl]amino}piperidine-1-carboxylate

HRID 715618Notes

Reaction equation

Cl[C:2]1[N:10]=[CH:9][N:8]=[C:7]2[C:3]=1[N:4]=[C:5]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[Cl:24])[N:6]2[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=1.[NH2:25][C@@H:26]1[CH2:31][CH2:30][CH2:29][N:28]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:27]1.C(N(CC)CC)C>C(O)C>[Cl:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[C:5]1[N:6]([C:11]2[CH:12]=[CH:13][C:14]([Cl:17])=[CH:15][CH:16]=2)[C:7]2[C:3]([N:4]=1)=[C:2]([NH:25][C@@H:26]1[CH2:31][CH2:30][CH2:29][N:28]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:27]1)[N:10]=[CH:9][N:8]=2

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 6-chloro-8-(2-chlorophenyl)-9-(4-chlorophenyl)-9H-purine (100 mg, 0.267 mmol, 1 eq.) in 3 mL of ethanol was added tert-butyl (3R)-3-aminopiperidine-1-carboxylate (64 mg, 0.32 mmol, 1.2 eq.) and triethylamine (0.06 mL, 0.4 mmol, 1.5 eq.). The reaction was heated to 80° C. for 16 h. The reaction was concentrated in vacuo. The crude material was purified by silica gel column chromatography using 0-100% ethyl acetate/hexanes to yield 124 mg (86%) of tert-butyl (3R)-3-{[8-(2-chlorophenyl)-9-(4-chlorophenyl)-9H-purin-6-yl]amino}piperidine-1-carboxylate. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.33 (br. s., 9 H) 1.49-1.67 (m, 2 H) 1.74 (d, J=6.97 Hz, 1 H) 2.00 (d, J=2.83 Hz, 1 H) 3.20 (br. s, 2 H) 3.50 (br. s, 1 H) 3.88 (br. s, 1 H) 4.32 (br. s., 1 H) 5.87 (d, J=7.44 Hz, 1 H) 7.02-7.54 (m, 8 H) 8.38 (s, 1 H), [M+H]+ 539.3.

Workup

concentrationThe reaction was concentrated in vacuo
customThe crude material was purified by silica gel column chromatography

Sources & evidence

ORD record: ord-bac033b4a0a44a90a438ecb577054434
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09187480B2

Reaction notes

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