Potassium Phosphate, Tribasic → HCID 86703768, compound

HRID 1849888Notes

Reaction equation

HRID 1849888 reaction equation
[CH:1]([N:14]1[CH2:19][CH2:18][N:17]([C:20](=[O:34])[CH2:21][C:22]2[C:31](I)=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[C:24]([F:33])[CH:23]=2)[CH2:16][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[CH2:19][CH2:18][N:17]([C:20](=[O:34])[CH2:21][C:22]2[C:31]([CH:35]3[CH2:37][CH2:36]3)=[CH:30][C:25]([C:26]([O:28][CH3:29])=[O:27])=[C:24]([F:33])[CH:23]=2)[CH2:16][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 86703766HCID 86703766, compound

Product 1

HCID 86703768HCID 86703768, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of methyl 4-(2-(4-benzhydrylpiperazin-1-yl)-2-oxoethyl)-2-fluoro-5-iodobenzoate (70 mg, 0.12 mmol), cyclopropylboronic acid (16 mg, 0.18 mmol), potassium phosphate (102 mg, 0.48 mmol) and tricyclohexylphosphine tetrafluoroborate (9 mg, 0.024 mmol) in toluene (2 mL) and water (0.1 mL) under a nitrogen atmosphere was added palladium acetate (8 mg, 0.037 mmol). The reaction mixture was heated to 100° C. for 18 hours then cooled to ambient temperature. The reaction mixture was quenched with water (10 mL), extracted with ethyl acetate (10 mL×3). The combined organic layers were washed with brine (10 mL), dried over anhydrous sodium sulfate, filtered and concentrated to afford the target compound (70 mg, crude) which was used in the next step without purification. LCMS (ESI): m/z: 486.9 [M+H]+.

Workup

  1. temperaturethen cooled to ambient temperature
  2. customThe reaction mixture was quenched with water (10 mL)
  3. extractionextracted with ethyl acetate (10 mL×3)
  4. washThe combined organic layers were washed with brine (10 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford the target compound (70 mg, crude) which
  9. customwas used in the next step without purification

Sources & evidence

ORD record
ord-cfdf56ff85894ddda98085d1cfc409fb
Source dataset
uspto-grants-2015_02
Patent number
US08952169B2

Reaction notes

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