Reaction SMILES: C(Cl)(Cl)[Cl:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:24][C:25]1[CH:30]=[CH:29][C:28]([NH:31][C:32]2[N:33]([CH3:54])[C:34]3[C:43]4[C:42](=[O:44])[NH:41][C:40]([CH:45](OC(=O)C)[CH:46]=[CH2:47])=[C:39]([CH3:52])[C:38]=4[CH:37]=[CH:36][C:35]=3[N:53]=2)=[C:27]([CH3:55])[CH:26]=1.[C:56]1([P:62]2(=[O:68])[CH2:67][CH2:66][NH:65][CH2:64][CH2:63]2)[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1>CO.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].C(OCC)C.C1COCC1>[ClH:2].[F:24][C:25]1[CH:30]=[CH:29][C:28]([NH:31][C:32]2[N:33]([CH3:54])[C:34]3[C:43]4[C:42](=[O:44])[NH:41][C:40]([CH:45]=[CH:46][CH2:47][N:65]5[CH2:64][CH2:63][P:62](=[O:68])([C:56]6[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=6)[CH2:67][CH2:66]5)=[C:39]([CH3:52])[C:38]=4[CH:37]=[CH:36][C:35]=3[N:53]=2)=[C:27]([CH3:55])[CH:26]=1
Reactant: ClC(Cl)Cl
Reactant: C=CC(OC(C)=O)c1[nH]c(=O)c2c(ccc3nc(Nc4ccc(F)cc4C)n(C)c32)c1C
Reactant: O=P1(c2ccccc2)CCNCC1
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CO
Solvent: C1CCOC1
Solvent: CCOCC
Product: Cc1cc(F)ccc1Nc1nc2ccc3c(C)c(C=CCN4CCP(=O)(c5ccccc5)CC4)[nH]c(=O)c3c2n1C
Product: Cl
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 52 %

Procedure:
To a 500 mL 3-neck round-bottom flask equipped with a magnetic stir-bar and internal thermometer was added Pd2(dba)3.HCCl3 (0.476 g, 0.46 mmole), triphenylphosphine (0.383 g, 1.5 mmol), and THF (100 mL). The resulting wine-red solution was stirred under a nitrogen atmosphere for 30 minutes. To the stirred solution was then added solid acetic acid 1-[2-(4-fluoro-2-methyl-phenylamino)-1,6-dimethyl-9-oxo-8,9-dihydro-1H-imidazo[4,5-h]isoquinolin-7-yl]-allyl ester (4.0 g, 9.2 mmole) in a single portion. An aqueous solution of 4-phenyl-[1,4]azaphosphinane 4-oxide free-base (200 mL, 0.106 M) was next added to the stirring solution over 3 minutes via an addition funnel. The temperature of the reaction immediately rose from 24° C. to 29.5° C. and maintained this temperature for about 20 minutes. After 1 hour, the reaction mixture had cooled to room temperature and a yellow precipitate had formed. The precipitate was isolated by filtration and washed with water followed by diethyl ether. The filter cake was re-dissolved in methanol (150 mL) and cooled over an ice bath. To the chilled solution with rapid stirring was added anhydrous HCl (10 mL, 1.25 M in methanol). The solution was then poured into a flask containing diethyl ether (600 mL) with stirring. Pentane (100 mL) was added, followed by additional anhydrous HCl (20 mL, 1.25 M in methanol). The resulting solution was decanted, leaving crude product as a gum on the sides of the flask. This material was re-dissolved in methanol (100 mL). Into the stirred solution was poured diethyl ether, resulting in a yellow flocculent precipitate. This was recovered by filtration and washed with diethyl ether to give 2-(4-fluoro-2-methyl-phenylamino)-1,6-dimethyl-7-[3-(4-oxo-4-phenyl-4λ5-[1,4]azaphosphinan-1-yl)-propenyl]-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one HCl salt (2.9 g, 52%). 1H NMR (400 MHz, CD3OD) δ 7.96-7.89 (m, 2H), 7.89 (d, 1H, J=9.0 Hz), 7.73 (d, 1H, J=9.0 Hz), 7.71-7.65 (m, 1H), 7.66-7.61 (m, 2H), 7.51 (dd, 1H, J1=5.5 Hz, J2=8.6 Hz), 7.32 (d, 1H, J=15.7 Hz), 7.26 (dd, 1H, J1=3.1 Hz, J2=9.4 Hz), 7.16 (td, 1H, J1=3.1 Hz, J2=8.6 Hz), 6.56-6.48 (m, 1H), 4.26 (s, 3H), 4.19 (d, 2H, J=7.0 Hz), 4.2-3.8 (br m, 2H), 3.8-3.6 (br m, 2H), 3.0-2.9 (br m, 2H), 2.47 (s, 3H), 2.37 (s, 3H), 2.5-2.3 (br m, 2H); ESMS m/z 569.7 (MH+).