Cesium carbonate → HCID 49805021, compound

HRID 576110Notes

Reaction equation

HRID 576110 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].Cl[C:31]1[N:32]=[N:33][C:34]([CH3:37])=[CH:35][CH:36]=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[N:32]=[N:33][C:34]([CH3:37])=[CH:35][CH:36]=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 2272543-Chloro-6-methylpyridazineHCID 5213051-Chloroethyl chloroformateHCID 66788241HCID 66788241, compound

Product 1

HCID 49805021HCID 49805021, compoundYield 3.5%

Reagents, catalysts & solvents 3

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

Procedure

Following the procedure in 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), 3-chloro-6-methylpyridazine (282 mg, 2.2 mmol), cesium carbonate (1.08 mg, 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 (471 mg, 2.2 mmol) and 1-chlorethyl chloroformate (0.48 mL, 4.4 mmol) gave 4-(3,4-dichlorophenyl)-6-fluoro-7-(6-methylpyridazin-3-yl)-1,2,3,4-tetrahydroisoquinoline (15 mg, 3%, 2 steps) as a green solid: 1H NMR (CDCl3, 500 MHz) δ 7.95 (d, J=7.8 Hz, 1H), 7.83 (dd, J=8.8, 1.9 Hz, 1H), 7.42-7.35 (m, 3H), 7.00 (dd, J=8.3, 1.9 Hz, 1H), 6.70 (d, J=12.0 Hz, 1H), 4.23-4.09 (m, 3H), 3.42 (dd, J=12.9, 5.3 Hz, 1H), 3.06 (dd, J=12.9, 6.7 Hz, 1H), 2.77 (s, 3H); ESI MS m/z 388, 390 [M+H]+.

Sources & evidence

ORD record
ord-ba47e17e6a384be3a5ad9f6310926f68
Source dataset
uspto-grants-2015_05
Patent number
US09034899B2

Reaction notes

Loading…