Cesium carbonate → HCID 131732856, compound

HRID 576104Notes

Reaction equation

HRID 576104 reaction equation
[F:1][C:2]([F:27])([F:26])S(OC1C=C2C([CH:11]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=3)[CH2:12]N(C)C2)=CC=1)(=O)=O.[C:28]([C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][CH:35]=1)#[N:29].[C:39](=O)([O-:41])[O-:40].[Cs+].[Cs+].C[N:46](C)[C:47]1[C:56]2[C:51](=[CH:52][CH:53]=[CH:54][C:55]=2N(C)C)C=CC=1.ClC(OC(Cl)C)=O>CN(C)C=O.O.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[F:27][C:2]([F:1])([F:26])[C:39]([OH:41])=[O:40].[Cl:25][C:20]1[CH:19]=[C:18]([CH:11]2[C:35]3[C:30](=[CH:31][C:32]([C:54]4[CH:55]=[C:56]([CH:51]=[CH:52][CH:53]=4)[C:47]#[N:46])=[CH:33][CH:34]=3)[CH2:28][NH:29][CH2:12]2)[CH:23]=[CH:22][C:21]=1[Cl:24]

Participants

9

Reactant 5

HCID 10796Cesium carbonateHCID 88675Proton spongeHCID 5213051-Chloroethyl chloroformateHCID 27343253-Cyanophenylboronic acidHCID 59580334HCID 59580334, compound

Product 1

HCID 131732856HCID 131732856, compoundYield 33.5%

Reagents, catalysts & solvents 3

HCID 53485975CID 53485975CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Following the procedure in Steps A and B of Example 14, 4-(3,4-dichlorophenyl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl trifluoromethanesulfonate (100 mg, 0.23 mmol), 3-cyanophenylboronic acid (51 mg, 0.35 mmol), cesium carbonate (225 mg, 0.69 mmol), and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (8 mg, 0.01 mmol) in N,N-dimethylformamide (2 mL) and water (1 mL) followed by N-de-methylation with N1,N1,N8,N8-tetramethylnaphthalene-1,8-diamine (52 mg, 0.24 mmol) and 1-chlorethyl chloroformate (0.08 mL, 0.72 mmol) gave 3-(4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydroisoquinolin-7-yl)benzonitrile, trifluoroacetate salt (38 mg, 33%, 2 steps) as an off-white solid: 1H NMR (CD3OD, 500 MHz) δ 8.01 (d, J=1.5 Hz, 1H), 7.97-7.95 (m, 1H), 7.75-7.73 (m, 1H), 7.66-7.63 (m, 2H), 7.60 (dd, J=8.2, 1.7 Hz, 1H), 7.49 (d, J=2.0 Hz, 1H), 7.49 (d, J=2.0 Hz, 1H), 7.23 (dd, J=8.3, 2.1 Hz, 1H), 7.04 (d, J=8.2 Hz, 1H), 4.65-4.52 (m, 3H), 3.83 (dd, J=12.6, 6.1 Hz, 1H), 3.51 (dd, J=12.6, 10.8 Hz, 1H); ESI MS m/z 379 [M+H]+.

Sources & evidence

ORD record
ord-4a88475a355946a38e17a384991fa3d9
Source dataset
uspto-grants-2015_05
Patent number
US09034899B2

Reaction notes

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