Potassium Phosphate, Tribasic → HCID 86703777, compound

HRID 1849899Notes

Reaction equation

HRID 1849899 reaction equation
[CH:1]([N:14]1[CH2:17][CH:16]([CH2:18][O:19][C:20]2[C:32](Cl)=[CH:31][C:23]([C:24]([NH:26][S:27]([CH3:30])(=[O:29])=[O:28])=[O:25])=[C:22]([F:34])[CH:21]=2)[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:35]1(B(O)O)[CH2:37][CH2:36]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].F[B-](F)(F)F.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:1]([N:14]1[CH2:17][CH:16]([CH2:18][O:19][C:20]2[C:32]([CH:35]3[CH2:37][CH2:36]3)=[CH:31][C:23]([C:24]([NH:26][S:27]([CH3:30])(=[O:29])=[O:28])=[O:25])=[C:22]([F:34])[CH:21]=2)[CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 20066521Tri(cyclohexyl)phosphine tetrafluoroborateHCID 86703776HCID 86703776, compound

Product 1

HCID 86703777HCID 86703777, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of product from step 1 (29.1 mg), cyclopropylboronic acid (31.4 mg), potassium phosphate (188 mg), palladium acetate (2.8 mg) and tricyclohexylphosphine tetrafluoroborate (8.8 mg) in toluene (1.2 mL) and water (0.06 mL) was heated at 95° C. for 16 hours. The contents were concentrated. The residue was diluted with EtOAc and washed with 1M NaH2PO4 and brine, and dried (Na2SO4). After filtration and concentration, the crude was purified with HPLC (10.3 mg). LCMS (Method D): RT=5.44 min, m/z: 509.2 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 11.78 (s, 1H), 7.46-7.38 (m, 4H), 7.29 (t, J=7.5 Hz, 4H), 7.18 (dd, J=18.0, 7.9 Hz, 3H), 6.96 (d, J=12.9 Hz, 1H), 4.54 (s, 1H), 4.22 (d, J=6.2 Hz, 2H), 3.07 (s, 2H), 2.89 (s, 1H), 2.13-1.98 (m, 1H), 0.96-0.83 (m, 2H), 0.72-0.61 (m, 2H).

Workup

  1. concentrationThe contents were concentrated
  2. additionThe residue was diluted with EtOAc
  3. washwashed with 1M NaH2PO4 and brine
  4. dry with materialdried (Na2SO4)
  5. filtrationAfter filtration and concentration
  6. customthe crude was purified with HPLC (10.3 mg)

Sources & evidence

ORD record
ord-90838d8d2c3e41f3afb456da7bf963ae
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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