Potassium Phosphate, Tribasic → HCID 56652712, compound

HRID 877872Notes

Reaction equation

HRID 877872 reaction equation
[F:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][N:10]([C:13]([C:15]3[CH:16]=[N:17][C:18](Br)=[CH:19][CH:20]=3)=[O:14])[CH2:9][CH2:8]2)=[CH:4][CH:3]=1.[CH2:24]([O:31][C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>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].C(O)CCC.O>[F:1][C:2]1[CH:23]=[CH:22][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][N:10]([C:13]([C:15]3[CH:16]=[N:17][C:18]([C:35]4[CH:36]=[CH:37][C:32]([O:31][CH2:24][C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=5)=[CH:33][CH:34]=4)=[CH:19][CH:20]=3)=[O:14])[CH2:9][CH2:8]2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27343144-Benzyloxy-phenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 58073332HCID 58073332, compound

Product 1

HCID 56652712HCID 56652712, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 22253497Water butanolSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of (4-(4-fluorobenzyl)piperazin-1-yl)(6-bromopyridin-3-yl)methanone (0.048 g, 0.13 mmol, 1.0 eq), 4-benzyloxyphenylboronic acid (0.040 g, 0.18 mmol, 1.4 eq), potassium phosphate (0.053 g, 0.25 mmol, 1.9 eq), S-Phos (0.006 g, 0.01 mmol, 0.1 eq), and tris(dibenzylideneacetone)dipalladium(0) (0.012 g, 0.01 mmol, 0.01 eq) was added 1-butanol-water (1.25 mL, 4:1). Following a 5 minute purge of the reaction mixture with argon, the reaction vessel was sealed and heated at 100° C. for 10 hours. The reaction mixture was filtered through Celite®, eluting with 5% MeOH—CH2Cl2 and purified by RP-HPLC to provide Compound 17. 1H nmr (D6-DMSO) δ 8.61 (1H, s), 8.06 (2H, d, J 9.0 Hz), 7.95 (1H, d, J 8.0 Hz), 7.83 (1H, dd, J 8.0, 2.0 Hz), 7.48-7.30 (7H, m), 7.16-7.10 (4H, m), 5.16 (2H, s), 3.61 (2H, m), 3.48 (2H, s), 3.37 (2H, m), 2.38 (4H, m); m/z: 483 [M+H]+.

Workup

  1. custompurge of the reaction mixture with argon
  2. customthe reaction vessel was sealed
  3. filtrationThe reaction mixture was filtered through Celite®
  4. washeluting with 5% MeOH—CH2Cl2
  5. custompurified by RP-HPLC

Sources & evidence

ORD record
ord-158ed8c56c7c4e5eb5d4ab597b47ccab
Source dataset
uspto-grants-2015_03
Patent number
US08987303B2

Reaction notes

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