2-Aminoadamantane hydrochloride → Tert-butyl 1'-((2-adamantyl)carbamoyl)spiro[indoline-3,4'-piperidine]-1-carboxylate

HRID 1424585Notes

Reaction equation

Cl.[CH:2]12[CH2:11][CH:6]3[CH2:7][CH:8]([CH2:10][CH:4]([CH2:5]3)[CH:3]1[NH2:12])[CH2:9]2.CCN(C(C)C)C(C)C.C1N=CN([C:27](N2C=NC=C2)=[O:28])C=1.[NH:34]1[CH2:39][CH2:38][C:37]2([C:47]3[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=3)[N:41]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[CH2:40]2)[CH2:36][CH2:35]1>C(Cl)Cl>[CH:2]12[CH2:11][CH:6]3[CH2:7][CH:8]([CH2:10][CH:4]([CH2:5]3)[CH:3]1[NH:12][C:27]([N:34]1[CH2:35][CH2:36][C:37]3([C:47]4[C:42](=[CH:43][CH:44]=[CH:45][CH:46]=4)[N:41]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])[CH2:40]3)[CH2:38][CH2:39]1)=[O:28])[CH2:9]2

Participants

Conditions

Temperature: 0 °C

Procedure

A stirred solution of 2-adamantanamine hydrochloride (81.1 mg, 0.432 mmol) and DIEA (557 mg, 4.32 mmol) in anhydrous CH2Cl2 (5 mL) was cooled to 0° C. and CDI (84 mg, 0.52 mmol) was added. The mixture was stirred for 1 h at 0° C. and tert-butyl spiro[indoline-3,4′-piperidine]-1-carboxylate (140 mg, 0.43 mmol) in anhydrous CH2Cl2 (5 mL) was added. The reaction mixture was allowed to warm to rt and stirred overnight. The reaction mixture was concentrated and the residue was purified by preparative TLC to provide tert-butyl 1′-((2-adamantyl)carbamoyl)spiro[indoline-3,4′-piperidine]-1-carboxylate as a white solid (50 mg, 25%). 1H NMR (CD3OD, 400 MHz): δ=1.58˜2.01 (m, 28H), 2.92 (t, 2H), 3.91 (d, 2H), 4.09 (d, 2H), 5.85 (d, 1H), 6.95˜7.85 (m, 4H); MS: 466 (M++1); LC-MS (4 min) tR=2.70 min, m/z=466.

Workup

temperatureto warm to rt
stirringstirred overnight
concentrationThe reaction mixture was concentrated
customthe residue was purified by preparative TLC

Sources & evidence

ORD record: ord-498ac49dcae2439089ad923b5869a0e0
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08927715B2

Reaction notes

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