2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 71509398, compound

HRID 1776808Notes

Reaction equation

HRID 1776808 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[O:18][CH2:17][N:8]3[C:9]4[CH:10]=[CH:11][CH:12]=[C:13]([F:16])[C:14]=4[CH:15]=[C:7]3[C:6]=2[CH:19]=1.[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[O:28][C:29]3[CH:39]=[C:38]([N:40]([CH3:45])[S:41]([CH3:44])(=[O:43])=[O:42])[C:37](B4OC(C)(C)C(C)(C)O4)=[CH:36][C:30]=3[C:31]=2[C:32]([NH:34][CH3:35])=[O:33])=[CH:23][CH:22]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>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].O>[F:16][C:13]1[C:14]2[CH:15]=[C:7]3[C:6]4[CH:19]=[C:2]([C:37]5[C:38]([N:40]([CH3:45])[S:41]([CH3:44])(=[O:43])=[O:42])=[CH:39][C:29]6[O:28][C:27]([C:24]7[CH:25]=[CH:26][C:21]([F:20])=[CH:22][CH:23]=7)=[C:31]([C:32]([NH:34][CH3:35])=[O:33])[C:30]=6[CH:36]=5)[CH:3]=[CH:4][C:5]=4[O:18][CH2:17][N:8]3[C:9]=2[CH:10]=[CH:11][CH:12]=1

Participants

6

Reactant 3

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 682394022-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamideHCID 71295475HCID 71295475, compound

Product 1

HCID 71509398HCID 71509398, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent2×

Conditions

Temperature
25 °C

Procedure

A mixture of 2-chloro-11-fluoro-6H-benzo[5,6][1,3]oxazino[3,4-a]indole (30 mg, 0.11 mmol), 2-(4-fluorophenyl)-N-methyl-6-(N-methylmethylsulfonamido)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzofuran-3-carboxamide (55 mg, 0.11 mmol), K3PO4.3H2O (88 mg, 0.33 mmol), Pd2(dba)3 (10 mg, 0.011 mmol), X-Phos (11 mg, 0.022 mmol) was stirred in dixane/H2O (5 mL, 4:1) at 110° C. for 12 hours. Then the mixture was cooled to 25° C., water was added to it. The mixture was extracted with ethyl acetate and washed with brine, dried over Na2SO4. After the combined organic layers were concentrated, the resulting residue was purified using prep-TLC (petroleum ether:EtOAc=3:1) to provide the product of Compound 43 (25 mg, yield: 40%). 1H-NMR (CDCl3, 400 MHz) δ 9.94˜7.97 (m, 2H), 7.83˜7.86 (m, 2H), 7.62 (s, 1H), 7.37˜7.40 (m, 1H), 7.09˜7.24 (m, 5H), 6.93 (s, 1H), 6.80˜6.85 (m, 1H), 5.95 (s, 2H), 5.85 (br, 1H), 3.16 (s, 3H), 3.00˜3.01 (d, J=5.2 Hz, 3H), 2.78 (s, 3H). MS (M+H)+: 614.

Workup

  1. extractionThe mixture was extracted with ethyl acetate
  2. washwashed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationAfter the combined organic layers were concentrated
  5. customthe resulting residue was purified

Sources & evidence

ORD record
ord-06a186726fe14ec98fb6e9911cc0fc77
Source dataset
uspto-grants-2016_02
Patent number
US09265773B2

Reaction notes

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