Binap, (A+-)- → Morpholin-4-yl(5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}biphenyl-3-yl)methanone

HRID 530388Notes

Reaction equation

HRID 530388 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][N:3]=1.[NH2:12][C:13]1[CH:14]=[C:15]([C:25]([N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)=[O:26])[CH:16]=[C:17]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:18]=1.CC(C)([O-])C.[Na+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.C(OCC)(=O)C.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]>[N:27]1([C:25]([C:15]2[CH:16]=[C:17]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[CH:18]=[C:13]([NH:12][C:2]3[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][N:3]=3)[CH:14]=2)=[O:26])[CH2:28][CH2:29][O:30][CH2:31][CH2:32]1

Participants

8

Reactant 4

HCID 634876Binap, (A+-)-HCID 27739122-Chloro-4-(trifluoromethyl)pyrimidineHCID 23676156Sodium t-butoxideHCID 90041595(5-Aminobiphenyl-3-yl)(morpholin-4-yl)methanone

Product 1

HCID 90041497Morpholin-4-yl(5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}biphenyl-3-yl)methanone

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-chloro-4-(trifluoromethyl)pyrimidine (34 mg, 0.186 mmol), (5-aminobiphenyl-3-yl)(morpholin-4-yl)methanone (63.1 mg, 0.224 mmol), sodium tert-butoxide, Pd2(dba)3 (9.64 mg, 0.009 mmol) and BINAP (11.6 mg, 0.019 mmol) in toluene (0.931 mL) was heated to 130° C. in a microwave reactor for 30 minutes, then allowed to cool to room temperature. The reaction mixture was diluted with ethyl acetate (30 mL) and was washed with 0.1 M HCl (30 mL) followed by brine (30 mL). The aqueous phases were further extracted with ethyl acetate (30 mL), then the combined organic extracts were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel column chromatography (ethyl acetate/hexanes) provided morpholin-4-yl(5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}biphenyl-3-yl)methanone as a white solid. MS ESI calc'd. for C22H20F3N4O2 [M+H]+ 429, found 429. 1H NMR (400 MHz, CDCl3): δ 8.69 (d, J=4.9 Hz, 1H); 7.92 (s, 1H); 7.80 (s, 1H); 7.71 (s, 1H); 7.63 (d, J=7.6 Hz, 2H); 7.48 (t, J=7.5 Hz, 2H); 7.40 (d, J=6.8 Hz, 2H); 7.15-7.03 (m, 1H); 3.97-3.44 (m, 8H).

Workup

  1. washwas washed with 0.1 M HCl (30 mL)
  2. extractionThe aqueous phases were further extracted with ethyl acetate (30 mL)
  3. dry with materialthe combined organic extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-06e36aa148a946778a428246119595ed
Source dataset
uspto-grants-2016_05
Patent number
US09353066B2

Reaction notes

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