Tri-o-tolylphosphine → HCID 69431616, compound

HRID 970008Notes

Reaction equation

HRID 970008 reaction equation
C[Sn](C)(C)[C:3]1[CH:17]=[CH:16][C:6]([O:7][CH:8]2[CH:13]3[CH2:14][CH2:15][N:10]([CH2:11][CH2:12]3)[CH2:9]2)=[CH:5][CH:4]=1.[I:20][C:21]1[CH:38]=[CH:37][C:24]2[N:25]3[CH2:31][N:29]([CH2:30][C:23]=2[CH:22]=1)[C:28]1[CH:32]=[CH:33][C:34](I)=[CH:35][C:27]=1[CH2:26]3.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[C:61]([OH:68])(=[O:67])/[CH:62]=[CH:63]/[C:64]([OH:66])=[O:65]>CN(C=O)C.CCOC(C)=O.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:61]([OH:68])(=[O:67])/[CH:62]=[CH:63]/[C:64]([OH:66])=[O:65].[N:10]12[CH2:15][CH2:14][CH:13]([CH2:12][CH2:11]1)[CH:8]([O:7][C:6]1[CH:16]=[CH:17][C:3]([C:34]3[CH:33]=[CH:32][C:28]4[N:29]5[CH2:31][N:25]([CH2:26][C:27]=4[CH:35]=3)[C:24]3[CH:37]=[CH:38][C:21]([I:20])=[CH:22][C:23]=3[CH2:30]5)=[CH:4][CH:5]=1)[CH2:9]2

Participants

8

Reactant 4

HCID 80271Tri-o-tolylphosphineHCID 444972Fumaric AcidHCID 11385953HCID 11385953, compoundHCID 21072606HCID 21072606, compound

Product 1

HCID 69431616HCID 69431616, compoundYield 74%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolventHCID 21584119Ethylacetate methanolSolvent

Procedure

The product of Example 28B (300 mg, 0.8 mmol) was coupled with the product of Example 28A (450 mg, 0.95 mmol) under the catalysis of Pd2(dba)3 (Aldrich, 30 mg, 0.033 mmol) and P(o-tolyl)3 (Aldrich, 30 mg, 0.1 mmol) in dry DMF (Aldrich, 4 mL) at 80° C. for 3 hours. It was then concentrated under reduced pressure and the free base of the title compound was purified by preparative HPLC (Xterra™, column, Xterra RP-18 5 μm, 30×100 mm. Eluting Solvent, MeCN/H2O(NH4HCO3, 0.1 M, pH=10) (v. 90/10 to 10/90 over 20 min.) Flow rate, 75 mL/min., uv, 250 nm) (60 mg, yield, 14%). The free base was treated with fumaric acid (Aldrich, 17 mg, 0.15 mmol) in EtOAc/MeOH (v.10:1, 5 mL) at ambient temperature for 10 hours to give the title compound (56 mg, 74%). 1H NMR (300 MHz, MeOH-D4) δ ppm 1.77-2.18 (m, 3H) 2.22-2.36 (m, 1H) 2.45-2.54 (m, 1H), 3.15-3.43 (m, 5H), 3.71-3.82 (m, J=14.9 Hz, 1H), 4.14-4.41 (m, 3H), 4.61-4.93 (m, 3H), 6.69 (s, 2H), 6.91-7.04 (m, 3H), 7.12-7.22 (m, J=8.8 Hz, 2H), 7.31-7.42 (m, 2H), 7.44-7.54 (m, 3H) ppm. MS (DCl/NH3) m/z 550 (M+H)+. Anal. Calculated for C28H28N3OI.1.15 C4H4O4: C, 57.33; H, 4.81; N, 6.15. Found: C, 57.13; H, 4.42; N, 6.22.

Workup

  1. concentrationIt was then concentrated under reduced pressure
  2. customthe free base of the title compound was purified by preparative HPLC (Xterra™, column, Xterra RP-18 5 μm, 30×100 mm. Eluting Solvent, MeCN/H2O(NH4HCO3, 0.1 M, pH=10) (v. 90/10 to 10/90 over 20 min.) Flow rate, 75 mL/min., uv, 250 nm) (60 mg, yield, 14%)

Sources & evidence

ORD record
ord-8893e29eef8b46eba6ca106c5a3811e4
Source dataset
uspto-grants-2007_12
Patent number
US07309699B2

Reaction notes

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