Acetic Acid → N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-2-fluoro-5-((tetrahydro-2H-pyran-4-yl)amino)benzamide

HRID 880324Notes

Reaction equation

[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([F:25])=[C:6]([CH:24]=1)[C:7]([NH:9][CH2:10][CH:11]([OH:23])[CH2:12][N:13]1[CH2:22][CH2:21][C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14]1)=[O:8].[O:26]1[CH2:31][CH2:30][C:29](=O)[CH2:28][CH2:27]1.CC(O)=O.[BH3-]C#N.[Na+]>CO>[CH2:14]1[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:21][CH2:22][N:13]1[CH2:12][CH:11]([OH:23])[CH2:10][NH:9][C:7](=[O:8])[C:6]1[CH:24]=[C:2]([NH:1][CH:29]2[CH2:30][CH2:31][O:26][CH2:27][CH2:28]2)[CH:3]=[CH:4][C:5]=1[F:25]

Participants

Conditions

Temperature: 17 °C

Procedure

A solution of 5-amino-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)-2-fluorobenzamide (372 mg, 1.08 mmol), dihydro-2H-pyran-4(3H)-one (108 mg, 1.08 mmol) and AcOH (0.05 mL) in MeOH (20 mL) was stirred at 17° C. for 2 h. Then NaBH3CN (109 mg, 1.63 mmol) was added and the resulting solution was stirred at 17° C. for 4 h. The solution was concentrated and the residue was purified by column chromatography to afford the title product (121.5 mg, Yield 17.5%). 1H NMR (CD3OD, 400 MHz): δ 7.16-7.07 (m, 3H), 7.03 (dd, J=2.9, 5.9 Hz, 2H), 6.95 (dd, J=8.9, 10.7 Hz, 1H), 6.79 (td, J=3.6, 8.8 Hz, 1H), 4.11 (quin, J=6.0 Hz, 1H), 3.98 (d, J=11.5 Hz, 2H), 3.80-3.69 (m, 2H), 3.64-3.40 (m, 5H), 2.98-2.81 (m, 4H), 2.72-2.60 (m, 2H), 1.99 (d, J=12.8 Hz, 2H), 1.56-1.39 (m, 2H). LCMS (m/z): 428.2 (M+1).

Workup

concentrationThe solution was concentrated
customthe residue was purified by column chromatography

Sources & evidence

ORD record: ord-449e49b4ab744ea8b883aa01129ec8af
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08993555B2

Reaction notes

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