Chloroacetyl chloride → 2-chloro-N-(isoquinolin-6-yl)acetamide

HRID 2378332Notes

Reaction equation

[NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][CH:6]=[CH:5]2.C(NC(C)C)(C)C.[Li].[Cl:20][CH2:21][C:22](Cl)=[O:23]>C1COCC1>[Cl:20][CH2:21][C:22]([NH:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][CH:6]=[CH:5]2)=[O:23]

Participants

Conditions

Temperature: -78 °C

Procedure

A 2.0-mL vial equipped with a stirrer bar was charged with 6-aminoisoquinoline (100 mg, 0.7 mmol) in THF (1.0 mL) and cooled to −78° C. Lithium diisopropylamine (40 μL, 0.35 mmol) was added to the reaction at −78° C. followed by dropwise addition of chloroacetylchloride (62 μL, 0.7 mmol). The reaction was allowed to warm to room temperature and stirred for 30 min. The reaction was concentrated in vacuo then the solid was triturated with cold methanol. The solid was collected by filtration to afford 2-chloro-N-isoquinolin-6-yl-acetamide (58 mg, 38%). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.14 (s, 2H) 8.01 (dd, J=9.08, 1.66 Hz, 1H) 8.45 (d, J=8.98 Hz, 2H) 8.66 (d, J=1.56 Hz, 1H) 11.46 (s, 1H); LCMS: 221 (M+H).

Workup

customA 2.0-mL vial equipped with a stirrer bar
temperatureto warm to room temperature
concentrationThe reaction was concentrated in vacuo
customthe solid was triturated with cold methanol
filtrationThe solid was collected by filtration

Sources & evidence

ORD record: ord-21885216a1dc4592b86583c19df0eb64
Source dataset: uspto-grants-2008_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07470787B2

Reaction notes

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