Furan → 6-[(1S)-2-amino-1-(3-fluorobenzyl)ethyl]-3-(4-chloro-1-methyl-1H-pyrazol-5-yl)-5,6-dihydro-7H-pyrrolo[3,4-b]pyridin-7-one

HRID 339986Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[N:4][N:5]([CH3:38])[C:6]=1[C:7]1[CH:8]=[C:9]2[CH2:15][N:14]([C@@H:16]([CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[CH:31]=3)[CH2:17][N:18]3C(=O)C4C(=CC=CC=4)C3=O)[C:13](=[O:37])[C:10]2=[N:11][CH:12]=1.O1C=CC=C1.NN>CO>[NH2:18][CH2:17][C@@H:16]([N:14]1[CH2:15][C:9]2[C:10](=[N:11][CH:12]=[C:7]([C:6]3[N:5]([CH3:38])[N:4]=[CH:3][C:2]=3[Cl:1])[CH:8]=2)[C:13]1=[O:37])[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[CH:31]=1

Participants

Conditions

Temperature: 50 °C

Procedure

2-[(2S)-2-[3-(4-Chloro-1-methyl-1H-pyrazol-5-yl)-7-oxo-5,7-dihydro-6H-pyrrolo [3,4-b]pyridin-6-yl]-3-(3-fluorophenyl)propyl]-1H-isoindole-1,3(2H)-dione (48 mg, 0.91) was dissolved in methanol (2 mL), tetrahydron furan (2 mL) and hydrazine (0.2 mL). The resulting reaction mixture was stirred at 50° C. for 2 h. Direct purification on prep.—HPLC (pH=10) afforded 12 mg (30.1% yield) of the desired intermediate as white solid. LC-MS found: 400.1 (M+H)+; 1H NMR (300 MHz, DMSO-d6) δ ppm: 8.78 (d, J=1.8 Hz, 1H), 8.32 (d, J=1.8 Hz, 1H), 7.74 (s, 1H), 7.26 (ddd, J1=7.8 Hz, J2=6.3 Hz, J3=8.1 Hz, 1H), 7.06 (m, 2H), 6.96 (dd, J1=8.7 Hz, J2=8.4 Hz, 1H), 4.51 (s, 2H), 4.34 (m, 1H), 3.80 (s, 3H), 3.01 (m, 2H), 2.91 (m, 2H).

Workup

customThe resulting reaction mixture
customDirect purification on prep.—HPLC (pH=10)

Sources & evidence

ORD record: ord-1ba46ac3b1dd47d8969b2322351a8352
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08895571B2

Reaction notes

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