2-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenyl → HCID 70977945, compound

HRID 628962Notes

Reaction equation

HRID 628962 reaction equation
[NH2:1][C@H:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]3[CH:13]=[N:14][N:15]([CH2:17][CH2:18][O:19][CH3:20])[CH:16]=3)[CH:10]=2)[N:5]([C:21](=[O:23])[CH3:22])[C@@H:4]([CH3:24])[CH2:3]1.Cl[C:26]1[CH:31]=[N:30][C:29]([CH3:32])=[CH:28][N:27]=1.CN(C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C.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]>[CH3:20][O:19][CH2:18][CH2:17][N:15]1[CH:16]=[C:12]([C:9]2[CH:10]=[C:11]3[C:6](=[CH:7][CH:8]=2)[N:5]([C:21](=[O:23])[CH3:22])[C@@H:4]([CH3:24])[CH2:3][C@H:2]3[NH:1][C:26]2[CH:31]=[N:30][C:29]([CH3:32])=[CH:28][N:27]=2)[CH:13]=[N:14]1

Participants

7

Reactant 4

HCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 126003862-Chloro-5-methylpyrazineHCID 23676156Sodium t-butoxideHCID 709775541-((2S,4R)-4-amino-6-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinolin-1(2H)-yl)ethanone

Product 1

HCID 70977945HCID 70977945, compoundYield 47%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

1-((2S,4R)-4-Amino-6-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinolin-1(2H)-yl)ethanone (for a preparation see Intermediate 7) (150 mg, 0.457 mmol), 2-chloro-5-methylpyrazine (147 mg, 1.142 mmol), Davephos (71.9 mg, 0.183 mmol), Pd2(dba)3 (84 mg, 0.091 mmol) and sodium tert-butoxide (132 mg, 1.370 mmol) were combined in 1,4-dioxane (4 ml) and the mixture heated at 120° C. for 25 min (microwave). The reaction mixture was partitioned between water (75 ml) and DCM (3×75 ml). The organics were combined, dried (hydrophobic frit) and evaporated under vacuum. The resulting brown oil was dissolved in DMSO (3×1 ml) and purified by MDAP (formate ×3). The solvent was evaporated under vacuum to give 1-((2S,4R)-6-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2-methyl-4-((5-methylpyrazin-2-yl)amino)-3,4-dihydroquinolin-1(2H)-yl)ethanone (91 mg, 0.216 mmol, 47% yield) as a yellow glass. LCMS (formate), Rt 0.75 min, MH+ 421.

Workup

  1. customThe reaction mixture was partitioned between water (75 ml) and DCM (3×75 ml)
  2. customdried (hydrophobic frit)
  3. customevaporated under vacuum
  4. dissolutionThe resulting brown oil was dissolved in DMSO (3×1 ml)
  5. custompurified by MDAP (formate ×3)
  6. customThe solvent was evaporated under vacuum

Sources & evidence

ORD record
ord-1d79a20fe4254a369584a3ec6a8022cb
Source dataset
uspto-grants-2016_04
Patent number
US09315487B2

Reaction notes

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