5-Amino-3-methylisoxazole → (R)-2-(4-cyano-3-(3-methylisoxazol-5-ylamino)phenylamino)-4-methylpentanamide

HRID 84812

Reaction equation

HRID 84812 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C@H:11]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:12]([NH2:14])=[O:13])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].[NH2:19][C:20]1[O:24][N:23]=[C:22]([CH3:25])[CH:21]=1.O.O.O.[O-]C1C=CC=CC=1.[Na+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>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]>[C:8]([C:7]1[CH:6]=[CH:5][C:4]([NH:10][C@H:11]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:12]([NH2:14])=[O:13])=[CH:3][C:2]=1[NH:19][C:20]1[O:24][N:23]=[C:22]([CH3:25])[CH:21]=1)#[N:9]

Participants

7

Reactant 4

HCID 845905-Amino-3-methylisoxazoleHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23681143Sodium Phenoxide TrihydrateHCID 67509372(R)-2-(3-bromo-4-cyanophenylamino)-4-methylpentanamide

Product 1

HCID 67508850(R)-2-(4-cyano-3-(3-methylisoxazol-5-ylamino)phenylamino)-4-methylpentanamideYield 15.8%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of (R)-2-(3-bromo-4-cyanophenylamino)-4-methylpentanamide (120 mg, 0.387 mmol), 5-amino-3-methylisoxazole (60 mg, 0.612 mmol), sodium phenoxide trihydrate (100 mg, 0.588 mmol), xantphos (25 mg, 0.043 mmol) and Pd2(dba)3 (20 mg, 0.021 mmol) in dioxane (3 mL) was degassed with Ar, then was heated at 170 C for 15 min by microwave. It was concentrated in vacuo. The residue was purified by HPLC to give (R)-2-(4-cyano-3-(3-methylisoxazol-5-ylamino)phenylamino)-4-methylpentanamide (20 mg).

Workup

  1. customwas degassed with Ar
  2. temperaturewas heated at 170 C for 15 min by microwave
  3. concentrationIt was concentrated in vacuo
  4. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-39e6f77a92524eb9a752a2c9685ff5c3
Source dataset
uspto-grants-2014_09
Patent number
US08846928B2

Linked notes

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