2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 90341040, compound

HRID 595706Notes

Reaction equation

HRID 595706 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]([C:17]([NH:19][CH3:20])=[O:18])=[C:15]3[C:10]([CH:11]=[C:12]([N:30]([CH3:35])[S:31]([CH3:34])(=[O:33])=[O:32])[C:13](B4OC(C)(C)C(C)(C)O4)=[CH:14]3)=[N:9]2)=[CH:4][CH:3]=1.Cl[C:37]1[CH:46]=[CH:45][C:44]2[CH2:43][CH2:42][N:41]3[C:47]4[CH:48]=[CH:49][CH:50]=[C:51]([F:54])[C:52]=4[CH:53]=[C:40]3[C:39]=2[N:38]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>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]>[F:54][C:51]1[C:52]2[CH:53]=[C:40]3[C:39]4[N:38]=[C:37]([C:13]5[C:12]([N:30]([CH3:35])[S:31]([CH3:34])(=[O:33])=[O:32])=[CH:11][C:10]6[C:15](=[C:16]([C:17]([NH:19][CH3:20])=[O:18])[N:8]([C:5]7[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=7)[N:9]=6)[CH:14]=5)[CH:46]=[CH:45][C:44]=4[CH2:43][CH2:42][N:41]3[C:47]=2[CH:48]=[CH:49][CH:50]=1

Participants

6

Reactant 3

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 90333462HCID 90333462, compoundHCID 903336312-Chloro-11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridine

Product 1

HCID 90341040HCID 90341040, compoundYield 24%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a degassed solution of 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-indazole-3-carboxamide (70 mg, 0.14 mmol), 2-chloro-11-fluoro-5,6-dihydroindolo[1,2-h][1,7]naphthyridine (46 mg, 0.17 mmol) and K3PO4.3H2O (112 mg, 0.42 mmol) in 1,4-dioxane (5 mL) was added Pd2(dba)3 (13 mg, 0.014 mmol) and X-Phos (14 mg, 0.028 mmol) under N2. The reaction mixture was heated to 100° C. and stirred for 3 hours, and then filtered through a celite pad. The filtrate was concentrated in vacuo, and the residue was purified by prep-HPLC to give the desired product (20 mg, yield: 24%). 1H-NMR (CDCl3, 400 MHz) δ 8.03 (s, 1H), 7.83 (s, 1H), 7.55˜7.60 (m, 1H), 7.52˜7.54 (m, 2H), 7.45 (s, 1H), 7.09˜7.19 (m, 5H), 6.73 (s, 1H), 6.30 (s, 1H), 6.20 (s, 1H), 4.28 (t, J=6.0 Hz, 2H), 3.32 (s, 3H), 3.25 (t, J=6.0 Hz, 2H), 2.92 (d, J=4.8 Hz, 3H), 2.76 (s, 3H). MS (M+H)+: 613.

Workup

  1. filtrationfiltered through a celite pad
  2. concentrationThe filtrate was concentrated in vacuo
  3. customthe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-beac37f7219443ceaab816597300de5b
Source dataset
uspto-grants-2016_01
Patent number
US09243002B2

Reaction notes

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