N-methyl-2-pyrrolidone → 2-{4-[(S)-7-(3-Fluoro-propyl)-2,7-diaza-spiro[4.4]non-2-yl]-phenyl}-6-hydroxy-3,4-dihydro-2H-isoquinolin-1-one

HRID 69442

Reaction equation

[CH2:1]1[C@@:5]2([CH2:9][CH2:8][NH:7][CH2:6]2)[CH2:4][CH2:3][N:2]1[C:10]1[CH:15]=[CH:14][C:13]([N:16]2[CH2:25][CH2:24][C:23]3[C:18](=[CH:19][CH:20]=[C:21]([OH:26])[CH:22]=3)[C:17]2=[O:27])=[CH:12][CH:11]=1.Br[CH2:29][CH2:30][CH2:31][F:32].C(=O)([O-])O.[Na+].CN1C(=O)CCC1>O.C(OCC)(=O)C>[F:32][CH2:31][CH2:30][CH2:29][N:7]1[CH2:8][CH2:9][C@@:5]2([CH2:1][N:2]([C:10]3[CH:15]=[CH:14][C:13]([N:16]4[CH2:25][CH2:24][C:23]5[C:18](=[CH:19][CH:20]=[C:21]([OH:26])[CH:22]=5)[C:17]4=[O:27])=[CH:12][CH:11]=3)[CH2:3][CH2:4]2)[CH2:6]1

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of 2-[(S)-4-(2,7-diaza-spiro[4.4]non-2-yl)-phenyl]-6-hydroxy-3,4-dihydro-2H-isoquinolin-1-one (0.20 g), 1-bromo-3-fluoro-propane (76 mg), sodium hydrogencarbonate (10 mg) and NMP (5 mL) was heated at 50° C. for 15 hours. The reaction mixture was distributed between ethyl acetate and water. The organic phase was dried over magnesium sulfate and concentrated. The raw product was purified by preparative HPLC. In this way the product was obtained with molecular weight 423.54 (C25H30FN3O2); MS (ESI): 424 (M+H+).

Workup

dry with materialThe organic phase was dried over magnesium sulfate
concentrationconcentrated
customThe raw product was purified by preparative HPLC
customIn this way the product was obtained with molecular weight 423.54 (C25H30FN3O2)

Sources & evidence

ORD record: ord-66e9a8fd87d04aea8e26a46ce96c38f2
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08822495B2

Linked notes

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