1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → tert-butyl (1S,2R)-2-(4-cyano-3-(1-methyl-1H-pyrazol-4-ylamino)phenylamino)cyclohexylcarbamate

HRID 2201033

Reaction equation

HRID 2201033 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:10][C@@H:11]2[CH2:16][CH2:15][CH2:14][CH2:13][C@@H:12]2[NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].Cl.Cl.[CH3:27][N:28]1[CH:32]=[C:31]([NH2:33])[CH:30]=[N:29]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]2[CH2:16][CH2:15][CH2:14][CH2:13][C@@H:12]2[NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:3][C:2]=1[NH:33][C:31]1[CH:30]=[N:29][N:28]([CH3:27])[CH:32]=1)#[N:9]

Participants

7

Reactant 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23681143Sodium Phenoxide TrihydrateHCID 448907531-methyl-1H-pyrazol-4-amine dihydrochlorideHCID 69283621tert-butyl (1S,2R)-2-(3-bromo-4-cyanophenylamino)cyclohexylcarbamate

Product 1

HCID 68077202tert-butyl (1S,2R)-2-(4-cyano-3-(1-methyl-1H-pyrazol-4-ylamino)phenylamino)cyclohexylcarbamateYield 32.1%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of tert-butyl (1S,2R)-2-(3-bromo-4-cyanophenylamino)cyclohexylcarbamate (150 mg, 0.380 mmol), 1-methyl-1H-pyrazol-4-amine dihydrochloride (80 mg, 0.470 mmol), sodium phenoxide trihydrate (300 mg, 1.76 mmol), xantphos (30 mg, 0.051 mmol) and Pd2(dba)3 (30 mg, 0.032 mmol) in dioxane (3 mL) was degassed with Ar, then was heated at 170 C for 30 min by microwave. It was concentrated in vacuo. The residue was purified by HPLC to give tert-butyl (1S,2R)-2-(4-cyano-3-(1-methyl-1H-pyrazol-4-ylamino)phenylamino)cyclohexylcarbamate (50 mg).

Workup

  1. customwas degassed with Ar
  2. temperaturewas heated at 170 C for 30 min by microwave
  3. concentrationIt was concentrated in vacuo
  4. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-dda4927a5eb1460480cda7cea3b7d7fb
Source dataset
uspto-grants-2016_06
Patent number
US09359375B2

Linked notes

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