Trifluoroacetic acid → 3-(1-Cyclopentyl-octahydro-pyrrolo[3,2-b]pyrrol-3-yl)-6-fluoro-1H-indole

HRID 1949624Notes

Reaction equation

C(OC([N:8]1[CH2:12][CH2:11][CH:10]2[N:13]([CH:26]3[CH2:30][CH2:29][CH2:28][CH2:27]3)[CH2:14][CH:15]([C:16]3[C:24]4[C:19](=[CH:20][C:21]([F:25])=[CH:22][CH:23]=4)[NH:18][CH:17]=3)[CH:9]12)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH:26]1([N:13]2[CH2:14][CH:15]([C:16]3[C:24]4[C:19](=[CH:20][C:21]([F:25])=[CH:22][CH:23]=4)[NH:18][CH:17]=3)[CH:9]3[NH:8][CH2:12][CH2:11][CH:10]23)[CH2:30][CH2:29][CH2:28][CH2:27]1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution containing 36 (2.0 g, 4.8 mmol) in DCM (20 mL) was cooled to 0° C. TFA (6 mL) was added and the pink reaction mixture was stirred at 0° C. After 1 h, the reaction mixture was warmed to ambient temperature then concentrated in vacuo. The residue was dissolved in EtOAc and the organic solution was washed successively with saturated aqueous NaHCO3 and brine, dried over anhydrous Na2SO4, filtered, and concentrated to afford 1.4 g of 37 which was used without further purification. 1H NMR (CDCl3, 300 MHz): δ8.50 (br s, 1H), 7.58 (dd, J=5.4, 8.4 Hz, 1H), 7.05-7.01 (m, 2H), 6.92-6.85 (m, 1H), 4.17-4.11 (m, 1H), 3.92 (app q, J=6.0 Hz, 1H), 3.74 (app q, J=6.6 Hz, 1H), 3.21-3.15 (m, 1H), 3.08-2.88 (m, 3H), 2.75-2.67 (m, 2H), 1.96-1.78 (m, 5H), 1.61 (m, 4H) ppm. Mass spectrum, m/z [314.2] (M+H)+.

Workup

temperaturethe reaction mixture was warmed to ambient temperature
concentrationthen concentrated in vacuo
dissolutionThe residue was dissolved in EtOAc
washthe organic solution was washed successively with saturated aqueous NaHCO3 and brine
dry with materialdried over anhydrous Na2SO4
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-e0bd399feedb429fac2c5c6b5200e27c
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08399683B2

Reaction notes

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