Cesium carbonate → Tert-butyl 2,2,2-trifluoro-1-(4-(4-phenylpyrimidin-2-ylamino)phenyl)ethylcarbamate

HRID 40742Notes

Reaction equation

HRID 40742 reaction equation
[C:1]1([C:7]2[CH:12]=[CH:11][N:10]=[C:9]([NH2:13])[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[C:15]1[CH:20]=[CH:19][C:18]([CH:21]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=1.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.C([O-])([O-])=O.[Cs+].[Cs+]>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].COCCOC>[F:23][C:22]([F:24])([F:25])[CH:21]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:30])[CH3:31])[C:18]1[CH:19]=[CH:20][C:15]([NH:13][C:9]2[N:8]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH:12]=[CH:11][N:10]=2)=[CH:16][CH:17]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 5987772-Amino-4-phenylpyrimidineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 68775432tert-Butyl (1-(4-bromophenyl)-2,2,2-trifluoroethyl)carbamate

Product 1

HCID 68774457Tert-butyl 2,2,2-trifluoro-1-(4-(4-phenylpyrimidin-2-ylamino)phenyl)ethylcarbamate

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-phenylpyrimidin-2-amine (70 mg, 0.4 mmol), tert-butyl 1-(4-bromophenyl)-2,2,2-trifluoroethylcarbamate (160 mg, 0.45 mmol), Xantphos (20 mg, 0.03 mmol), Pd2(dba)3 (20 mg, 0.02 mmol), Cs2CO3 (160 mg, 0.5 mmol) and DME (1.0 mL) was placed in a sealed tube and heated up to 100° C. in a microwave (Biotage, Model: Initiator) for 30 min. The reaction mixture was filtered through a pad of Celite, washed with ethyl acetate, and concentrated in vacuo. The resulting crude residue was purified by chromatography on silica gel (ethyl acetate/hexanes) to give tert-butyl 2,2,2-trifluoro-1-(4-(4-phenylpyrimidin-2-ylamino)phenyl)ethylcarbamate. 1H NMR (CDCl3, 400 MHz) δ 8.41 (dd, 1H), 8.01-7.98 (m, 2H), 7.70 (d, 2H), 7.46-7.42 (m, 3H), 7.28 (d, 2H), 7.12 (d, 1H). MS (ESI) 445 (M+H).

Workup

  1. customwas placed in a sealed tube
  2. filtrationThe reaction mixture was filtered through a pad of Celite
  3. washwashed with ethyl acetate
  4. concentrationconcentrated in vacuo
  5. customThe resulting crude residue was purified by chromatography on silica gel (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-9bbb3d60cdbd4afeb4133dea283da887
Source dataset
uspto-grants-2013_09
Patent number
US08530480B2

Reaction notes

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