1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → HCID 58299615, compound

HRID 79126Notes

Reaction equation

HRID 79126 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[NH2:21][C:22]1[N:23]=[CH:24][C:25]2[C:30]3[CH:31]=[CH:32][NH:33][C:34](=[O:35])[C:29]=3[N:28]([CH:36]3[CH2:40][CH2:39][CH2:38][CH2:37]3)[C:26]=2[N:27]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC(C)([O-])C.[Na+]>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]>[CH:36]1([N:28]2[C:26]3[N:27]=[C:22]([NH:21][C:2]4[N:7]=[N:6][C:5]([N:8]5[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]5)=[CH:4][CH:3]=4)[N:23]=[CH:24][C:25]=3[C:30]3[CH:31]=[CH:32][NH:33][C:34](=[O:35])[C:29]2=3)[CH2:37][CH2:38][CH2:39][CH2:40]1

Participants

7

Reactant 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 21925370tert-Butyl 4-(6-chloropyridazin-3-yl)piperazine-1-carboxylateHCID 23676156Sodium t-butoxideHCID 58299710HCID 58299710, compound

Product 1

HCID 58299615HCID 58299615, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

A mixture of tert-butyl 4-(6-chloropyridazin-3-yl)piperazine-1-carboxylate (0.060 g, 0.20 mmol), compound 83 (0.054 g, 0.20 mmol), Xantphos (0.017 g, 0.030 mmol), Pd2(dba)3 (0.014 g, 0.015 mmol), and sodium tert-butoxide (0.029 g, 0.30 mmol) in dioxane was purged with nitrogen gas for 1 minute. The reaction was heated at 120° C. for 6 hours and then cooled to room temperature. The solvent was removed by filtration. The residue was washed with 2×1 ml dioxane. The product was then dissolved in 10 mL methanol/DCM (1:1) and concentrated. The crude material was re-dissolved in 4 mL methanol and purified on a C-18 reversephase column (150×30 mm, 4 micro) using Mass directed preperative HPLC and gradient elution of acetonitrile in water containing 0.1% TFA to give the title compound 162. LCMS-ESI (POS), M/Z, M+1: 532.3

Workup

  1. customwas purged with nitrogen gas for 1 minute
  2. temperaturecooled to room temperature
  3. customThe solvent was removed by filtration
  4. washThe residue was washed with 2×1 ml dioxane
  5. dissolutionThe product was then dissolved in 10 mL methanol/DCM (1:1)
  6. concentrationconcentrated
  7. dissolutionThe crude material was re-dissolved in 4 mL methanol
  8. custompurified on a C-18 reversephase column (150×30 mm, 4 micro)
  9. washHPLC and gradient elution of acetonitrile in water containing 0.1% TFA

Sources & evidence

ORD record
ord-fec263e3066040e589c536907f45fa42
Source dataset
uspto-grants-2014_09
Patent number
US08841312B2

Reaction notes

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