2-Dicyclohexylphosphino-2',6'-diisopropoxybiphenyl → HCID 89815181, compound

HRID 525417Notes

Reaction equation

HRID 525417 reaction equation
[CH3:1][C:2]1([CH3:20])[O:6][C:5](=[O:7])[N:4]([CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[C@H:3]1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.Br[C:22]1[CH:23]=[C:24]2[N:30]([C:31]3[N:36]=[CH:35][CH:34]=[CH:33][N:32]=3)[CH:29]=[CH:28][C:25]2=[N:26][CH:27]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC(C)C)=CC=CC=2OC(C)C)CCCCC1.CC(C)([O-])C.[Na+]>COC1C=CC=C(OC)C=1C1C(P(C2CCCCC2)C2CCCCC2)=CC=CC=1.C1C=[C-]C=C(CCN)C=1.[Cl-].[Pd+2].ClCCl>[CH3:1][C:2]1([CH3:20])[O:6][C:5](=[O:7])[N:4]([CH:8]2[CH2:9][CH2:10][N:11]([C:22]3[CH:23]=[C:24]4[N:30]([C:31]5[N:36]=[CH:35][CH:34]=[CH:33][N:32]=5)[CH:29]=[CH:28][C:25]4=[N:26][CH:27]=3)[CH2:12][CH2:13]2)[C@H:3]1[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 162179852-Dicyclohexylphosphino-2',6'-diisopropoxybiphenylHCID 23676156Sodium t-butoxideHCID 89813611HCID 89813611, compoundHCID 89815427HCID 89815427, compound

Product 1

HCID 89815181HCID 89815181, compound

Reagents, catalysts & solvents 1

HCID 131735588HCID 131735588, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

A glass microwave reaction vessel was charged with (S)-5,5-dimethyl-4-phenyl-3-(piperidin-4-yl)oxazolidin-2-one (50 mg, 0.182 mmol), 6-bromo-1-(pyrimidin-2-yl)-1H-pyrrolo[3,2-b]pyridine (50.1 mg, 0.182 mmol), 2-dicyclohexylphosphino-2′,6′-di-i-propoxy-1,1′-biphenyl (8.50 mg, 0.018 mmol, Sigma-Aldrich), chloro(2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl)[2-(2-aminoethylphenyl)]palladium(II)-dichloromethane (13.81 mg, 0.018 mmol, Sigma-Aldrich) and sodium tert-butoxide (26.3 mg, 0.273 mmol). The vessel was capped and evacuated and refilled with argon three times. Dioxane (364 μl) was then added to the reaction mixture. The mixture was stirred and heated at 100° C. overnight. After cooling to room temperature, the material was purified by Waters Auto purification HPLC (Column: Xbridge 19×100 mm; Flow rate: 40 mL/min; Mobile phase: 0.1% NH4OH in ACN and water; Gradient: 20-75% B in 8 min with total run time of 10 min) to provide (S)-5,5-dimethyl-4-phenyl-3-(1-(1-(pyrimidin-2-yl)-1H-pyrrolo[3,2-b]pyridin-6-yl)piperidin-4-yl)oxazolidin-2-one as a white solid. 1H NMR (500 MHz, DMSO-d6) δ 8.73 (d, J=5.56 Hz, 2H), 8.52-8.60 (m, 1H), 8.32 (d, J=4.49 Hz, 1H), 8.07-8.20 (m, 1H), 7.26-7.42 (m, 3H), 7.15-7.25 (m, 4H), 6.63 (d, J=3.53 Hz, 1H), 4.59 (s, 1H), 3.70 (d, J=11.22 Hz, 1H), 3.51-3.64 (m, 2H), 2.76 (qt, J=2.89, 12.50 Hz, 1H), 2.04-2.18 (m, 1H), 1.83-1.94 (m, 1H), 1.59-1.70 (m, 1H), 1.48-1.58 (m, 1H), 1.46 (s, 3H), 0.80 (s, 3H). m/z (ESI) 469.2 (M+H)+.

Workup

  1. customA glass microwave reaction vessel
  2. customThe vessel was capped
  3. customevacuated
  4. additionrefilled with argon three times
  5. additionDioxane (364 μl) was then added to the reaction mixture
  6. temperatureAfter cooling to room temperature
  7. customthe material was purified by Waters Auto purification HPLC (Column: Xbridge 19×100 mm; Flow rate: 40 mL/min; Mobile phase: 0.1% NH4OH in ACN and water; Gradient: 20-75% B in 8 min with total run time of 10 min)

Sources & evidence

ORD record
ord-0af70983ed2f446bb1841bb9c7f858f0
Source dataset
uspto-grants-2016_05
Patent number
US09340549B2

Reaction notes

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