Potassium Phosphate, Tribasic → HCID 57918478, compound

HRID 1908244Notes

Reaction equation

HRID 1908244 reaction equation
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][CH2:9][CH:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[OH:11])[CH:3]=1.[F:18][C:19]([F:30])([F:29])[C:20]1[CH:21]=[C:22](B(O)O)[CH:23]=[CH:24][CH:25]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC([O-])=O.CC([O-])=O.[Pd+2].C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2]>[C:12]1([C@@H:10]([OH:11])[CH2:9][NH:8][C:4]2[CH:3]=[C:2]([C:24]3[CH:23]=[CH:22][CH:21]=[C:20]([C:19]([F:30])([F:29])[F:18])[CH:25]=3)[N:7]=[CH:6][N:5]=2)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27343883-(Trifluoromethyl)phenylboronic acidHCID 61277948HCID 61277948, compound

Product 1

HCID 57918478HCID 57918478, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 12976736Bis(ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane);iron(2+)Catalyst

Procedure

To a round bottomed flask were added 2-[(6-chloropyrimidin-4-yl)amino]-1-phenylethanol (62.4 mg, 0.25 mmol), 3-trifluoromethylphenyl boronic acid (71.2 mg, 0.38 mmol), K3PO4 (106.1 mg, 0.5 mmol), Pd(OAc)2 (8.4 mg, 0.013 mmol) and 1,1′-bis(di-tert-butylphosphino)-ferrocene (5.9 mg, 0.013 mmol). The flask was then evacuated, backfilled with N2, and charged with 1,4-dioxane (2.5 mL). The reaction mixture was heated at reflux for 2.5 h, before cooling to rt, diluting with EtOAc (15 mL), washing with water (2×10 mL), drying, and concentrating to dryness. The crude residue was purified (FCC) to yield the title compound (35.7 mg, 40%). MS (ESI): mass calcd. for C19H16F3N3O, 359.1; m/z found, 360.2 [M+H]+. 1H NMR (CD3OD): 8.50 (s, 1H), 8.23 (s, 1H), 8.15 (d, J=7.8 Hz, 1H), 7.78 (d, J=8.1 Hz, 1H), 7.69 (t, J=7.8 Hz, 1H), 7.44 (d, J=7.3 Hz, 2H), 7.37-7.33 (m, 2H), 7.28-7.24 (m, 1H), 6.96 (s, 1H), 4.93-4.90 (m, 1H), 3.79-3.69 (m, 1H), 3.61 (dd, J=13.6, 7.8 Hz, 1H).

Workup

  1. customThe flask was then evacuated
  2. additioncharged with 1,4-dioxane (2.5 mL)
  3. temperatureThe reaction mixture was heated
  4. temperatureat reflux for 2.5 h
  5. additiondiluting with EtOAc (15 mL)
  6. washwashing with water (2×10 mL)
  7. customdrying
  8. concentrationconcentrating to dryness
  9. customThe crude residue was purified (FCC)

Sources & evidence

ORD record
ord-6ce2bdff4aa64d22a93e116c412ce278
Source dataset
uspto-grants-2013_12
Patent number
US08598202B2

Reaction notes

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