2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 76684525, compound

HRID 2202650Notes

Reaction equation

HRID 2202650 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[CH:5]=[N:6][CH:7]=1.[CH2:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:17][CH2:16][N:15]1[CH2:24][CH:25]([OH:34])[CH2:26][N:27]1[CH2:32][CH2:31][NH:30][CH2:29][C:28]1=[O:33].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.CC([O-])(C)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.[Pd]>[CH2:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:17][CH2:16][N:15]1[CH2:24][CH:25]([OH:34])[CH2:26][N:27]1[CH2:32][CH2:31][N:30]([C:2]2[CH:7]=[N:6][CH:5]=[C:4]([N:8]3[CH2:13][CH2:12][O:11][CH2:10][CH2:9]3)[CH:3]=2)[CH2:29][C:28]1=[O:33]

Participants

7

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 467396144-(5-Bromopyridin-3-yl)morpholineHCID 86728091HCID 86728091, compound

Product 1

HCID 76684525HCID 76684525, compoundYield 3.3%

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A solution of 4-(5-bromopyridin-3-yl)morpholine (100 mg, 0.413 mmol), 1-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)piperazin-2-one (119 mg, 0.413 mmol), X-phos (20 mg, 0.042 mmol), Pd(dba)2 (10 mg, 0.017 mmol) and NaOtBu (59.0 mg, 0.615 mmol) in dioxane (5 mL) was heated at 120° C. 1 h under microwave conditions. The crude reaction mixture was filtered, concentrated, and purified by preparative HPLC purification. (6.10 mg, yield 3.3%) 1H NMR (MeOD, 400 MHz), δ ppm: 7.76 (d, J=2.3 Hz, 1H), 7.72 (d, J=2.0 Hz, 1H), 7.17-7.07 (m, 3H), 7.07-7.01 (m, 1H), 6.89-6.80 (m, 1H), 4.28-4.18 (m, 1H), 3.93 (s, 2H), 3.89-3.82 (m, 4H), 3.82-3.72 (m, 4H), 3.71-3.63 (m, 1H), 3.59 (t, J=1.0 Hz, 2H), 3.32-3.28 (m, 1H), 3.27-3.16 (m, 4H), 2.99-2.90 (m, 2H), 2.90-2.81 (m, 2H), 2.68-2.58 (m, 2H).

Workup

  1. custom1 h
  2. customThe crude reaction mixture
  3. filtrationwas filtered
  4. concentrationconcentrated
  5. custompurified by preparative HPLC purification

Sources & evidence

ORD record
ord-f3817aad837c4cec92e37e8bba94bb3d
Source dataset
uspto-grants-2016_06
Patent number
US09365555B2

Reaction notes

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