Potassium Phosphate, Tribasic → 3,4-dihydroisoquinolin-1(2H)-one

HRID 1505040Notes

Reaction equation

Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6](C[C@H]1COC(C)(C)O1)[C:7]2=[O:12].ClC1C=CC(N)=CC=1C1NC(C2C=CC=CC=2)=CN=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.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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:7]1(=[O:12])[C:8]2[C:3](=[CH:2][CH:11]=[CH:10][CH:9]=2)[CH2:4][CH2:5][NH:6]1

Participants

Conditions

Temperature: 96 °C

Procedure

To a round-bottom flask under argon containing (S)-5-bromo-2-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-3,4-dihydroisoquinolin-1(2H)-one (227 mg, 0.79 mmol), 4-chloro-3-(5-phenyl-1H-imidazol-2-yl)aniline (213 mg, 0.79 mmol), Pd2(dba)3 (143 mg, 0.158 mmol), xantphos (260 mg, 0.316 mmol), potassium phosphate (505 mg, 2.37 mmol) is added anhydrous dioxane (1.6 ml). The mixture is stirred at 96° C. for 18 hours, cooled to room temperature, filtered through a celite pad and washed with THF. The crude product is purified by flash column chromatography using 1% methanol in dichloromethane as eluent to give S)-5-(4-Chloro-3-(5-phenyl-1H-imidazol-2-yl)phenylamino)-2-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-3,4-dihydroisoquinolin-1(2H)-one as a dark brown solid. LC-MS m/z: 530.1 (M+1).

Workup

temperaturecooled to room temperature
filtrationfiltered through a celite pad
washwashed with THF
customThe crude product is purified by flash column chromatography

Sources & evidence

ORD record: ord-b82561ad785549328eb3238ea7fbd712
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09216964B2

Reaction notes

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