Cesium carbonate → 6-{4-[(2R)-2-Hydroxy-2-(4-methyl-1-oxo-1,3-dihydro-2-benzofuran-5-yl)ethyl]-2-oxopiperazin-1-yl}thieno-[2,3-b]pyridine-2-carbonitrile

HRID 1465791Notes

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.Cl[C:23]1[N:28]=[C:27]2[S:29][C:30]([C:32]#[N:33])=[CH:31][C:26]2=[CH:25][CH:24]=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+]>O1CCOCC1.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[N:28]=[C:27]3[S:29][C:30]([C:32]#[N:33])=[CH:31][C:26]3=[CH:25][CH:24]=2)[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 [I-10] (33 mg, 0.11 mmol), 6-chlorothieno[2,3-b]pyridine-2-carbonitrile [I-13] (22 mg, 0.11 mmol), Pd2(dba)3 (21 mg, 0.023 mmol), Xantphos (26 mg, 0.045 mmol), and Cs2CO3 (55 mg, 0.17 mmol) in dioxane (2 mL) was sealed in a microwave tube and purged three times with nitrogen. It was heated to 120° C. for 20 minutes in a microwave reactor. LC showed formation of the title product, which was purified by silica gel flash chromatography. LC-MS (IE, m/z): 449 [M+1]+.

Workup

customwas sealed in a microwave tube
custompurged three times with nitrogen
customwas purified by silica gel flash chromatography

Sources & evidence

ORD record: ord-ab0c8008544b4753937743639f771478
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08999991B2

Reaction notes

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