2-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl → HCID 178423403, compound

HRID 540070Notes

Reaction equation

HRID 540070 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=2)[N:5]=[C:4]([N:13]2[CH2:19][C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=3[S:16](=[O:25])(=[O:24])[CH2:15][CH2:14]2)[CH:3]=1.[NH2:26][C@H:27]1[CH2:32][CH2:31][C@H:30]([OH:33])[CH2:29][CH2:28]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.CC(C)([O-])C.[Na+]>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].O1CCOCC1>[O:24]=[S:16]1(=[O:25])[C:17]2[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=2[CH2:19][N:13]([C:4]2[CH:3]=[C:2]([NH:26][C@H:27]3[CH2:32][CH2:31][C@H:30]([OH:33])[CH2:29][CH2:28]3)[C:11]3[C:6](=[CH:7][CH:8]=[C:9]([CH3:12])[CH:10]=3)[N:5]=2)[CH2:14][CH2:15]1

Participants

7

Reactant 4

HCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 23676156Sodium t-butoxideHCID 712545984-(4-Chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxideHCID 178511715HCID 178511715, compound

Product 1

HCID 178423403HCID 178423403, compound

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

A mixture of 4-(4-chloro-6-methylquinolin-2-yl)-2,3,4,5-tetrahydro-1,4-benzothiazepine 1,1-dioxide (140 mg, 0.38 mmol, prepared in analogy to the one in Example 2-1), trans-4-aminocyclohexanol (45 mg, 0.39 mmol), tris(dibenzylideneacetone)dipalladium(0) (35 mg, 0.038 mmol), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (15 mg, 0.038 mmol), sodium tert-butoxide (38 mg, 0.39 mmol) and 1,4-dioxane (2 mL) was heated with stirring in a 5 mL of microwave process vial for 2 hours at 120° C. under microwave irradiation. The mixture was filtered and washed with ethyl acetate. The filtrate was washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by preparative HPLC to afford the product as a solid. MS obsd. (ESI+) [(M+H)+] 452, 1H NMR (400 MHz, DMSO-d6) δ ppm 7.98-7.83 (m, 2 H), 7.76 (s, 1 H), 7.64-7.44 (m, 2 H), 7.29 (d, J=8.34 Hz, 1 H), 7.21 (d, J=8.84 Hz, 1 H), 6.22 (d, J=8.34 Hz, 1 H), 6.06 (s, 1 H), 5.09 (brs, 2 H), 4.68 (d, J=4.29 Hz, 1 H), 3.62 (brs, 3 H), 3.49 (d, J=4.55 Hz, 1 H), 2.34 (s, 3 H), 2.03-1.83 (m, 4 H), 1.63-1.45 (m, 2 H), 1.35 (brs, 2 H), 1.24 (brs, 1 H), 1.18 (brs, 1 H).

Workup

  1. temperaturewas heated
  2. filtrationThe mixture was filtered
  3. washwashed with ethyl acetate
  4. washThe filtrate was washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-1fb85b30e54f430b962319449ce1dd45
Source dataset
uspto-grants-2014_10
Patent number
US08871756B2

Reaction notes

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