Cesium carbonate → HCID 49805024, compound

HRID 576112Notes

Reaction equation

HRID 576112 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[C:18]3[C:13](=[CH:14][C:15](B4OC(C)(C)C(C)(C)O4)=[C:16]([F:19])[CH:17]=3)[CH2:12][N:11](C)[CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].Br[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([S:37]([CH3:40])(=[O:39])=[O:38])[CH:32]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)C1C2C(=CC=CC=2N(C)C)C=CC=1.ClC(OC(Cl)C)=O>CN(C)C=O.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[C:18]3[C:13](=[CH:14][C:15]([C:31]4[CH:36]=[CH:35][CH:34]=[C:33]([S:37]([CH3:40])(=[O:39])=[O:38])[CH:32]=4)=[C:16]([F:19])[CH:17]=3)[CH2:12][NH:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

9

Reactant 5

HCID 10796Cesium carbonateHCID 88675Proton spongeHCID 5213051-Chloroethyl chloroformateHCID 2757146Benzene, 1-bromo-3-(methylsulfonyl)-HCID 66788241HCID 66788241, compound

Product 1

HCID 49805024HCID 49805024, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Following the procedure of Step A and Step B of Example 19, 4-(3,4-dichlorophenyl)-6-fluoro-2-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroisoquinoline (500 mg, 1.1 mmol), 1-bromo-3-(methylsulfonyl)benzene (517 mg, 2.2 mmol), cesium carbonate (1.08 g, 3.3 mmol), and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) (44 mg, 0.06 mmol) in N,N-dimethylformamide (10 mL) and water (3 mL) followed by N-de-methylation with N1,N1,N8,N8-tetramethylnaphthalene-1,8-diamine (240 mg, 1.12 mmol) and 1-chlorethyl chloroformate (0.31 mL, 2.8 mmol) gave after purification by preparative HPLC followed by preparative thin layer chromatography (90:10:1 diethyl ether/methanol/concentrated ammonium hydroxide) 4-(3,4-dichlorophenyl)-6-fluoro-7-(3-(methylsulfonyl)phenyl)-1,2,3,4-tetrahydroisoquinoline (38 mg, 15%) as a colorless oil: 1H NMR (CDCl3, 500 MHz) δ 8.10 (s, 1H), 7.94 (d, J=7.5 Hz, 1H), 7.84 (d, J=7.5 Hz, 1H), 7.65 (dd, J=8.0, 8.0 Hz, 1H), 7.41 (d, J=8.0 Hz, 1H), 7.26 (s, 1H), 7.20 (d, J=7.5 Hz, 1H), 7.01 (dd, J=8.0, 2.0 Hz, 1H), 6.71 (d, J=11.0 Hz, 1H), 4.20-4.09 (m, 3H), 3.43 (dd, J=13.0, 5.5 Hz, 1H), 3.10 (s, 3H), 3.07 (dd, J=13.0, 6.5 Hz, 1H), 2.04 (br s, 1H); ESI MS m/z 450 [M+H]+

Workup

  1. customgave
  2. customafter purification by preparative HPLC

Sources & evidence

ORD record
ord-a5d51db71338434cb87ce223f083c166
Source dataset
uspto-grants-2015_05
Patent number
US09034899B2

Reaction notes

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