HCID 118214741, compound → HCID 118207714, compound

HRID 2205601Notes

Reaction equation

[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH:12]1[CH2:17][CH2:16][CH2:15][N:14]([C:18]2[CH:19]=[C:20]3[N:36]([CH3:37])[CH:35]=[CH:34][C:21]3=[N:22][C:23]=2[C@@H:24]([NH:26]C(=O)OC(C)(C)C)[CH3:25])[CH2:13]1>Cl.O1CCOCC1>[NH2:26][C@H:24]([C:23]1[N:22]=[C:21]2[CH:34]=[CH:35][N:36]([CH3:37])[C:20]2=[CH:19][C:18]=1[N:14]1[CH2:15][CH2:16][CH2:17][C@H:12]([N:3]2[C:4](=[O:11])[C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[C:2]2=[O:1])[CH2:13]1)[CH3:25]

Participants

Conditions

Temperature: 20 °C

Procedure

A mixture of tert-butyl ((1S)-1-(6-(3-(1,3-dioxoisoindolin-2-yl)piperidin-1-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethyl)carbamate (100 mg, 0.59 mmol) in HCl/dioxane (10 mL) was stirred at 20° C. for 2 hours. The mixture was concentrated in vacuo and the residue was purified by preparative HPLC to give title diastereomers. Peak 2 (longer retention time, 20 mg, 18% yield): 1H NMR (400 MHz, CD3OD) δ ppm 7.90-7.98 (m, 1H), 7.68-7.77 (m, 4H), 7.40 (d, J=3.0 Hz, 1H), 6.50 (d, J=3.1 Hz, 1H), 5.07 (q, J=6.6 Hz, 1H), 4.04-4.16 (m, 1H), 3.75 (s, 3H), 3.59-3.74 (m, 3H), 2.79-2.94 (m, 1H), 2.21-2.32 (m, 1H), 1.82-2.13 (m, 3H), 1.69 (d, J=6.8 Hz, 3H); ESI-MS m/z [M+H]+ calc'd for C23H25N5O2, 404. found 404. Peak 1 (shorter retention time, 30 mg, 27% yield): 1H NMR (400 MHz, CD3OD) δ 7.85 (s, 1H), 7.64-7.57 (m, 4H), 7.32-7.26 (m, 1H), 6.35 (d, J=2.4 Hz, 1H), 5.29 (q, J=6.9 Hz, 1H), 4.20-4.08 (m, 1H), 3.85-3.70 (m, 2H), 3.67 (s, 3H), 3.45 (ddd, J=5.1, 7.4, 9.0 Hz, 1H), 2.95-2.86 (m, 1H), 2.34-2.22 (m, 1H), 2.12-2.00 (m, 2H), 1.82 (qd, J=8.5, 12.2 Hz, 1H), 1.65 (d, J=6.8 Hz, 3H); ESI-MS m/z [M+H]+ calc'd for C23H25N5O2, 404. found 404.

Workup

concentrationThe mixture was concentrated in vacuo
customthe residue was purified by preparative HPLC
customto give title diastereomers

Sources & evidence

ORD record: ord-ec682cf5361647c5a27b1b502c5ef4cf
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09371321B2

Reaction notes

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