Potassium Phosphate, Tribasic → HCID 59618747, compound

HRID 1691442Notes

Reaction equation

HRID 1691442 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([N:14]2[C:20]3[C:21](Cl)=[CH:22][CH:23]=[CH:24][C:19]=3[NH:18][C:17]3[N:26]=[C:27]([C:30]([F:33])([F:32])[F:31])[CH:28]=[CH:29][C:16]=3[CH2:15]2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[N:34]1[CH:39]=[CH:38][CH:37]=[C:36](B(O)O)[CH:35]=1.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC([O-])=O.CC([O-])=O.[Pd+2].C1(C)C=CC=CC=1.O>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([N:14]2[C:20]3[C:21]([C:36]4[CH:35]=[N:34][CH:39]=[CH:38][CH:37]=4)=[CH:22][CH:23]=[CH:24][C:19]=3[NH:18][C:17]3[N:26]=[C:27]([C:30]([F:33])([F:32])[F:31])[CH:28]=[CH:29][C:16]=3[CH2:15]2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27343783-Pyridinylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 66901760HCID 66901760, compound

Product 1

HCID 59618747HCID 59618747, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 22272177Toluene waterSolvent

Procedure

A mixture of intermediate 25 (30 mg, 0.06 mmol), 3-pyridine boronic acid (74 mg, 0.60 mmol), Pd(OAc)2 (13 mg, 0.06 mmol), S-Phos (49 mg, 0.12 mmol) and K3PO4 (100 mg) in 4 mL 99:1 v:v toluene/H2O was heated at 150° C. for 40 min in a microwave reactor. After cooling to rt, the reaction mixture was concentrated and the residue was purified by silica gel chromatography (10-100% EtOAC/hexanes) to afford the title compound as a racemic mixture. 1H NMR (500 MHz, (CD3)2CO): δ 8.62 (s, 1H), 8.58 (d, 1H), 8.42 (s, 1H), 7.82 (d, 1H), 7.75 (d, 1H), 7.40 (m, 2H), 7.20 (d, 2H), 7.16 (d, 1H), 7.14 (m, 1H), 7.02 (d, 2H), 5.20 (d, 1H), 4.85 (d, 1H), 1.23 (s, 9H). LC-MS: m/z 539.2 (M+H)+. The racemic mixture was separated by HPLC using a chiralcel OD-H column and 20% EtOH/hexanes as the mobile phase. The fastest eluting isomer (E1) has a retention time of 12.0 min, the slower eluting isomer (E2) has a retention time of 20 min.

Workup

  1. concentrationthe reaction mixture was concentrated
  2. customthe residue was purified by silica gel chromatography (10-100% EtOAC/hexanes)

Sources & evidence

ORD record
ord-70dc4baffad1401598441b4705b608c6
Source dataset
uspto-grants-2012_04
Patent number
US08153626B2

Reaction notes

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