Potassium Phosphate, Tribasic → HCID 57918588, compound

HRID 1908255Notes

Reaction equation

HRID 1908255 reaction equation
Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][CH2:9][C@@H:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[OH:11])[CH:3]=1.[F:18][C:19]1([F:37])[O:23][C:22]2[CH:24]=[CH:25][C:26](B3OC(C)(C)C(C)(C)O3)=[CH:27][C:21]=2[O:20]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>[F:37][C:19]1([F:18])[O:20][C:21]2[CH:27]=[CH:26][C:25]([C:2]3[N:7]=[CH:6][N:5]=[C:4]([NH:8][CH2:9][C@@H:10]([C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=4)[OH:11])[CH:3]=3)=[CH:24][C:22]=2[O:23]1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 113121312,2-difluoro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzo[1,3]dioxoleHCID 86635140HCID 86635140, compound

Product 1

HCID 57918588HCID 57918588, compoundYield 83%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

(1R)-2-[(6-Chloropyrimidin-4-yl)amino]-1-phenylethanol (75 mg, 0.30 mmol), 2,2-difluoro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzo[1,3]dioxole (85 mg, 0.30 mmol), Pd(OAc)2 (1.3 mg, 0.006 mmol, 2 mol %), 2-dicyclohexylphosphino-2′,6′-dimethoxy-1,1′-biphenyl (S-Phos) (4.9 mg, 0.012 mmol, 4 mol %) and K3PO4 (191 mg, 0.900 mmol) were dissolved in dioxane (1.0 mL), which had been degassed by bubbling N2 into the solvent and water (0.1 mL) in a sealed tube. The tube was flushed with N2 and heated at 100° C. for 16 h before cooling to rt and filtering through a pad of celite. The celite was washed with CH2Cl2 (5 mL) and the filtrate concentrated to dryness. The crude material was purified by (FCC) to yield the title compound (92 mg, 83%). MS (ESI): mass calcd. for C19H15F2N3O3, 371.11; m/z found, 372.1 [M+H]+. 1H NMR (CDCl3): 8.64 (s, 1H), 7.73-7.71 (m, 2H), 7.43-7.37 (m, 4H), 7.34-7.30 (m, 1H), 7.14-7.12 (m, 1H), 6.65 (d, J=1.1 Hz, 1H), 5.31-5.25 (br hump, 1H), 5.01-4.99 (m, 1H), 3.91-3.85 (br hump, 1H), 3.64-3.59 (m, 1H).

Workup

  1. customwhich had been degassed
  2. customby bubbling N2 into the solvent and water (0.1 mL) in a sealed tube
  3. customThe tube was flushed with N2
  4. temperaturebefore cooling to rt
  5. filtrationfiltering through a pad of celite
  6. washThe celite was washed with CH2Cl2 (5 mL)
  7. concentrationthe filtrate concentrated to dryness
  8. customThe crude material was purified by (FCC)

Sources & evidence

ORD record
ord-d29cf2ad79a54850af6d33eefafdf2b7
Source dataset
uspto-grants-2013_12
Patent number
US08598202B2

Reaction notes

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