2-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl → HCID 67313212, compound

HRID 1716409Notes

Reaction equation

HRID 1716409 reaction equation
[C:1]1([CH:7]([NH:9][C:10]([C:12]2[S:13][C:14]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24]4[CH:29]=[CH:28][CH:27]=[C:26](Br)[CH:25]=4)[N:18]=3)=[CH:15][CH:16]=2)=[O:11])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:31][N:32]([CH3:38])[CH:33]1[CH2:37][CH2:36][NH:35][CH2:34]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1>C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1COCC1.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.C(Cl)(Cl)Cl.[Pd].[Pd]>[C:1]1([CH:7]([NH:9][C:10]([C:12]2[S:13][C:14]([C:17]3[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([N:35]5[CH2:36][CH2:37][CH:33]([N:32]([CH3:38])[CH3:31])[CH2:34]5)[CH:25]=4)[N:18]=3)=[CH:15][CH:16]=2)=[O:11])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

7

Reactant 3

HCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 27585193-(Dimethylamino)pyrrolidineHCID 67313462HCID 67313462, compound

Product 1

HCID 67313212HCID 67313212, compoundYield 500%

Reagents, catalysts & solvents 3

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)CatalystHCID 8028TetrahydrofuranSolventHCID 2733832Lithium HexamethyldisilazideSolvent

Conditions

Temperature
65 °C

Procedure

5-[2-(3-Bromo-phenylamino)-pyrimidin-4-yl]-thiophene-2-carboxylic acid (1-phenyl-ethyl)-amide (20 mg, 41 μmol), 3-dimethylamino pyrrolidine (6 mg, 0.5 μmol), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (1.5 mg, 2 μmol), and 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (2 mg, 5 μmol) were suspended in 0.2 mL lithium bis(trimethylsilyl)amide solution in THF (1M). The reaction mixture was stirred at 65° C. for 48 hours. The reaction was quenched with 1 mL MeOH and concentrated and the crude product was redissolved in DMSO and purified by mass triggered reverse phase HPLC to afford 1.2 mg of pure 5-{2-[3-(3-Dimethylamino-pyrrolidin-1-yl)-phenylamino]-pyrimidin-4-yl}-thiophene-2-carboxylic acid (1-phenyl-ethyl)-amide (2.5 μmol, 6%, 1:1 mixture of diastereomers). 1H NMR (500 MHz, DMSO-d6) δ 9.45 (s, 1H), 8.94 (d, J=8 Hz, 1H), 8.50 (d, J=5 Hz, 1H), 7.97 (d, J=4 Hz, 1H), 7.92 (d, J=4 Hz, 1H), 7.39 (d, J=5 Hz, 2H), 7.33 (m, 4H), 7.23 (t, J=7 Hz, 1H), 7.18 (s, 1H), 6.98 (m, 1H), 6.17 (d, J=7.5 Hz, 1H), 5.14 (quintet, J=6.5 Hz, 1H), 3.45 (q, J=8 Hz, 1H), 3.39 (t, J=8 Hz, 1H), 3.32 (m, 2H), 3.02 (q, J=8 Hz, 1H), 2.77 (m, 1H), 2.15 (s, 6H), 1.79 (m, 1H), 1.49 (d, J=6.5 Hz, 3H). MS: m/z 513 (M+H+).

Workup

  1. customThe reaction was quenched with 1 mL MeOH
  2. concentrationconcentrated
  3. dissolutionthe crude product was redissolved in DMSO
  4. custompurified by mass triggered reverse phase HPLC

Sources & evidence

ORD record
ord-bdd946014a2448718ae987b5246349c2
Source dataset
uspto-grants-2010_09
Patent number
US07803806B2

Reaction notes

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