1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → HCID 59186503, compound

HRID 336417Notes

Reaction equation

HRID 336417 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([N:7]2[CH:11]=[C:10]([NH2:12])[CH:9]=[N:8]2)[CH2:3][CH2:2]1.I[C:14]1[N:32]=[C:17]2[CH:18]=[CH:19][CH:20]=[C:21]([C:22]3[CH:27]=[CH:26][CH:25]=[C:24]([S:28]([CH3:31])(=[O:30])=[O:29])[CH:23]=3)[N:16]2[N:15]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.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]>[CH3:31][S:28]([C:24]1[CH:23]=[C:22]([C:21]2[N:16]3[N:15]=[C:14]([NH:12][C:10]4[CH:9]=[N:8][N:7]([CH:4]5[CH2:3][CH2:2][O:1][CH2:6][CH2:5]5)[CH:11]=4)[N:32]=[C:17]3[CH:18]=[CH:19][CH:20]=2)[CH:27]=[CH:26][CH:25]=1)(=[O:29])=[O:30]

Participants

7

Reactant 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 510637031-(Tetrahydro-2H-pyran-4-YL)-1H-pyrazol-4-amineHCID 59186411HCID 59186411, compound

Product 1

HCID 59186503HCID 59186503, compoundYield 11%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
160 °C

Procedure

A suspension of 1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-amine (50.0 mg, 0.299 mmol, 1.2 equiv), 2-iodo-5-(3-(methylsulfonyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridine (0.100 g, 0.249 mmol, 1 equiv), tris(dibenzylideneacetone)dipalladium (0) (17.0 mg, 0.019 mmol, 0.075 equiv), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (21.6 mg, 0.037 mmol, 0.150 equiv), and sodium tert-butoxide in dioxane (2 mL) was heated at 160° C. for 15 min under microwave radiation. The reaction mixture was partitioned between half saturated aqueous sodium chloride solution and ethyl acetate. The aqueous layer was extracted with ethyl acetate (2×). The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and concentrated. Purification by preparative HPLC provided product (11.5 mg, 11% yield). 1H NMR (400 MHz, DMSO-d6), δ: 9.28 (s, 1H), 8.79 (s, 1H), 8.35 (d, J=7.9 Hz, 1H), 8.13 (d, J=8.0 Hz, 1H), 7.87 (dd, J=16.6, 8.8 Hz, 2H), 7.66 (dd, J=8.7, 7.3 Hz, 1H), 7.55 (m, 1H), 7.40 (m, 1H), 7.21 (m, 1H), 4.31 (m, 1H), 3.95 (d, J=11.1 Hz, 2H), 3.52-3.39 (m, 2H), 2.07 (s, 3H), 1.89 (m, 4H).

Workup

  1. customThe reaction mixture was partitioned between half saturated aqueous sodium chloride solution and ethyl acetate
  2. extractionThe aqueous layer was extracted with ethyl acetate (2×)
  3. dry with materialThe combined organic extracts were dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-f728c78ce7b5450b826e7337e403ceea
Source dataset
uspto-grants-2014_11
Patent number
US08889673B2

Reaction notes

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