Ethyl Acetate → (S)-10-(2-Hydroxymethyl-azetidin-1-yl)-5,6,8,9-tetrahydro-1,4,7,10a-tetraaza-cyclohepta[f]indene-7-carboxylicacid tert-butyl ester

HRID 528727Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:22][CH2:21][C:12]2=[C:13](Cl)[N:14]3[C:18]([N:19]=[C:11]2[CH2:10][CH2:9]1)=[CH:17][CH:16]=[N:15]3)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl.[NH:24]1[CH2:27][CH2:26][C@H:25]1[CH2:28][OH:29].CCN(C(C)C)C(C)C.CCOC(C)=O>C(O)C>[C:1]([O:5][C:6]([N:8]1[CH2:22][CH2:21][C:12]2=[C:13]([N:24]3[CH2:27][CH2:26][C@H:25]3[CH2:28][OH:29])[N:14]3[C:18]([N:19]=[C:11]2[CH2:10][CH2:9]1)=[CH:17][CH:16]=[N:15]3)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 80 °C

Procedure

To 50 mg (0.155 mmol) 10-chloro-5,6,8,9-tetrahydro-1,4,7,10a-tetraaza-cyclohepta[f]indene-7-carboxylic acid tert-butyl ester (route 1, from step a to d) and 22 mg (0.17 mmol) (S)-azetidin-2-yl-methanol hydrogen chloride in 2 mL ethanol was added 2 mL (0.31 mmol) DIPEA, and the reaction mixture was heated at 80° C. for 19 hours. The reaction was cooled to room temperature and 20 mL EtOAc was added. The organic layer was washed with 10 mL citric acid (1 M), H2O (2×10 mL), 10 mL saturated brine, and dried over MgSO4. After evaporation of the solvent the product was purified by column chromatography (silica, heptane/EtOAc 1:5).

Workup

temperatureThe reaction was cooled to room temperature
washThe organic layer was washed with 10 mL citric acid (1 M), H2O (2×10 mL), 10 mL saturated brine
dry with materialdried over MgSO4
customAfter evaporation of the solvent the product
customwas purified by column chromatography (silica, heptane/EtOAc 1:5)

Sources & evidence

ORD record: ord-7e44baf37c59477cb209921dbccaf563
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346816B2

Reaction notes

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