Cesium carbonate → Tert-butyl 4-(7-cyanoisoquinolin-3-yl)-3-oxopiperazine-1-carboxylate

HRID 1465743Notes

Reaction equation

Cl[C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([C:12]#[N:13])[CH:6]=2.[O:14]=[C:15]1[NH:20][CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:16]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[C:12]([C:7]1[CH:6]=[C:5]2[C:10]([CH:11]=[C:2]([N:20]3[CH2:19][CH2:18][N:17]([C:21]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:22])[CH2:16][C:15]3=[O:14])[N:3]=[CH:4]2)=[CH:9][CH:8]=1)#[N:13]

Participants

Conditions

Temperature: 100 °C

Procedure

To a flask charged with 3-chloroisoquinoline-7-carbonitrile (250 mg, 1.3 mmol) and a stir bar was added tert-butyl 3-oxopiperazine-1-carboxylate (400 mg, 2.0 mmol), Pd2(dba)3 (120 mg, 0.13 mmol), Xantphos (150 mg, 0.26 mmol), cesium carbonate (650 mg, 2.0 mmol), and dioxane (20 mL). The mixture was purged three times with nitrogen, and heated to 100° C. for 16 hours. The mixture was diluted with EtOAc, washed with brine, dried over sodium sulfate, adsorbed onto silica gel, and purified by silica gel chromatography (Hexanes:EtOAc) to provide tert-butyl 4-(7-cyanoisoquinolin-3-yl)-3-oxopiperazine-1-carboxylate. LC-MS (IE, m/z): 353 [M+1]+.

Workup

customThe mixture was purged three times with nitrogen
additionThe mixture was diluted with EtOAc
washwashed with brine
dry with materialdried over sodium sulfate
custompurified by silica gel chromatography (Hexanes:EtOAc)

Sources & evidence

ORD record: ord-e99bc2b2a71e4dcbaee2175cbb7c4458
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08999991B2

Reaction notes

Loading…