Cesium carbonate → 4-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]-1-[2-(methylsulfonyl)quinolin-6-yl]piperazin-2-one

HRID 1465798Notes

Reaction equation

[OH:1][C@H:2]([C:11]1[CH:20]=[CH:19][C:14]2[C:15](=[O:18])[O:16][CH2:17][C:13]=2[C:12]=1[CH3:21])[CH2:3][N:4]1[CH2:9][CH2:8][NH:7][C:6](=[O:10])[CH2:5]1.Br[C:23]1[CH:24]=[C:25]2[C:30](=[CH:31][CH:32]=1)[N:29]=[C:28]([S:33]([CH3:36])(=[O:35])=[O:34])[CH:27]=[CH:26]2.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+]>CN(C=O)C.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]>[OH:1][C@H:2]([C:11]1[CH:20]=[CH:19][C:14]2[C:15](=[O:18])[O:16][CH2:17][C:13]=2[C:12]=1[CH3:21])[CH2:3][N:4]1[CH2:9][CH2:8][N:7]([C:23]2[CH:24]=[C:25]3[C:30](=[CH:31][CH:32]=2)[N:29]=[C:28]([S:33]([CH3:36])(=[O:34])=[O:35])[CH:27]=[CH:26]3)[C:6](=[O:10])[CH2:5]1

Participants

Conditions

Temperature: 120 °C

Procedure

A mixture of 4-[(2R)-2-hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]piperazin-2-one (66 mg, 0.23 mmol), 6-Bromo-2-(methylsulfonyl)quinoline [I-14] (65 mg, 0.23 mmol), Pd2(dba)3 (42 mg, 0.045 mmol), Xantphos (53 mg, 0.091 mmol), and Cs2CO3 (110 mg, 0.34 mmol) in DMF (5 mL) was sealed in a microwave tube and purged three times with nitrogen. It was heated to 120° C. for 10 minutes in a microwave reactor. LC showed formation of the product. The material was purified by silica gel flash chromatography, followed by crystallization to give the title product. LC-MS (IE, m/z): 496 [M+1]+.

Workup

customwas sealed in a microwave tube
custompurged three times with nitrogen
customThe material was purified by silica gel flash chromatography
customfollowed by crystallization

Sources & evidence

ORD record: ord-9cf66603d17145a1b31620f6a6d7c3ff
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08999991B2

Reaction notes

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