Hydrazine → (2S)-N-((1R)-2-amino-1-[4-((S)-2-methylbutoxy)phenyl]-ethyl)-2-phenylpropionamide

HRID 1874642Notes

Reaction equation

O=C1C2C(=CC=CC=2)C(=O)[N:3]1[CH2:12][C@H:13]([NH:26][C:27](=[O:36])[C@H:28]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH3:29])[C:14]1[CH:19]=[CH:18][C:17]([O:20][CH2:21][C@@H:22]([CH3:25])[CH2:23][CH3:24])=[CH:16][CH:15]=1.NN>CCO.CCOC(C)=O>[NH2:3][CH2:12][C@H:13]([NH:26][C:27](=[O:36])[C@H:28]([C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)[CH3:29])[C:14]1[CH:15]=[CH:16][C:17]([O:20][CH2:21][C@@H:22]([CH3:25])[CH2:23][CH3:24])=[CH:18][CH:19]=1

Participants

Conditions

Temperature: 55 °C

Procedure

To a solution of (S)-N-{(R)-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-1-[4-((S)-2-methyl-butoxy)-phenyl]-ethyl}-2-phenyl-propionamide dissolved in 10 mL of EtOH, was added anhydrous hydrazine. The resulting mixture was heated to 55° C. 1.5 h. It was cooled to rt, and diluted with EtOAc. The solids were filtered off, and the filtrate concentrated and was purified by column chromatography on silica gel using 0%→10% MeOH/DCM to obtain 109 mg (96%) of the desired product. 1H NMR (400 MHz, MeOD) δ 7.19-7.33 (m, 5H), 7.05-7.12 (m, 2H), 6.79-6.88 (m, 2H), 5.12 (dd, J=8.8, 5.8 Hz, 1H), 3.77-3.86 (m, 1H), 3.69-3.77 (m, 2H), 3.21-3.29 (m, 2H), 1.81 (s, 1H), 1.57 (ddd, J=13.4, 7.6, 5.8 Hz, 1H), 1.47 (d, J=6.8 Hz, 3H), 1.22-1.35 (m, 1H), 1.02 (d, J=6.8 Hz, 3H), 0.96 (t, J=7.5 Hz, 3H); LCMS m/e calcd 355.2 [(M+H)+, for C22H31N2O2 355.2].

Workup

custom1.5 h
temperatureIt was cooled to rt
filtrationThe solids were filtered off
concentrationthe filtrate concentrated
customwas purified by column chromatography on silica gel using 0%→10% MeOH/DCM

Sources & evidence

ORD record: ord-bc1485f7a4374364840d5c3768e2cabf
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08304577B2

Reaction notes

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