Triethylamine → 7-{6-[(3,3-Dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-3-pyridinyl}-5,7-diazaspiro[3.4]octane-6,8-dione

HRID 527692Notes

Reaction equation

[NH2:1][C:2]1([C:6]([NH:8][C:9]2[CH:10]=[N:11][C:12]([O:15][C:16]3[C:21]4[C:22]([CH3:26])([CH3:25])[CH2:23][O:24][C:20]=4[CH:19]=[CH:18][CH:17]=3)=[CH:13][CH:14]=2)=[O:7])[CH2:5][CH2:4][CH2:3]1.C(N(CC)CC)C.Cl[C:35](Cl)([O:37]C(=O)OC(Cl)(Cl)Cl)Cl>ClCCl>[CH3:25][C:22]1([CH3:26])[C:21]2[C:16]([O:15][C:12]3[N:11]=[CH:10][C:9]([N:8]4[C:6](=[O:7])[C:2]5([CH2:5][CH2:4][CH2:3]5)[NH:1][C:35]4=[O:37])=[CH:14][CH:13]=3)=[CH:17][CH:18]=[CH:19][C:20]=2[O:24][CH2:23]1

Participants

Conditions

Temperature: 0 °C

Procedure

1-amino-N-{6-[(3,3-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-3-pyridinyl}cyclobutanecarboxamide (Intermediate 70, 17 mg) was dissolved in dry dichloromethane (1.8 ml). The reaction mixture was cooled down in an ice bath. Triethylamine (39.48 μl, 0.283 mmol) was added at 0° C. Then 0.89 ml of a solution of triphosgene in dry dichloromethane was added dropwise (0.0135 mg, 4.00 mg). The reaction mixture was stirred under argon during 10 min at 0° C., then during 30 min at room temperature. Then an additional 0.25 equivalent of triphosgene in dichloromethane (0.26 M solution) was added at 0° C. and the reaction mixture was stirred under argon an additional 30 min at room temperature. The solvents were removed under vacuum. The residue obtained was purified by flash chromatography on silica gel (Companion system, 4 g silica cartridge) with cyclohexane/ethylacetate as eluents from 100/0 to 55/45. This afforded the title compound (12 mg).

Workup

temperatureThe reaction mixture was cooled down in an ice bath
waitduring 30 min at room temperature
stirringthe reaction mixture was stirred under argon an additional 30 min at room temperature
customThe solvents were removed under vacuum
customThe residue obtained
customwas purified by flash chromatography on silica gel (Companion system, 4 g silica cartridge) with cyclohexane/ethylacetate as eluents from 100/0 to 55/45

Sources & evidence

ORD record: ord-8236b984068a4aa2995d3af2fe160e2e
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346790B2

Reaction notes

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