Potassium Phosphate, Tribasic → HCID 71061072, compound

HRID 872061Notes

Reaction equation

HRID 872061 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C@H:9]2[CH2:11][C@@H:10]2[CH2:12][O:13][C:14]2[C:23](B(O)O)=[CH:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][N:20]=3)[N:15]=2)=[N:7][CH:8]=1.Br[C:28]1[S:32][C:31]([CH3:33])=[N:30][C:29]=1[CH3:34].[O-]P([O-])([O-])=O.[K+].[K+].[K+].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>C1COCC1.O.CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:33][C:31]1[S:32][C:28]([C:23]2[C:14]([O:13][CH2:12][C@H:10]3[CH2:11][C@@H:9]3[C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][N:7]=3)=[N:15][C:16]3[C:21]([CH:22]=2)=[N:20][CH:19]=[CH:18][CH:17]=3)=[C:29]([CH3:34])[N:30]=1

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2986285-Bromo-2,4-dimethyl-1,3-thiazoleHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 131732547HCID 131732547, compound

Product 1

HCID 71061072HCID 71061072, compound

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (2-{[(1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl]methoxy}-1,5-naphthyridin-3-yl)boronic acid (PP1) (25 mg, 0.050 mmol), 5-bromo-2,4-dimethyl-1,3-thiazole (9.6 mg, 0.050 mmol), K3PO4 (21.2 mg, 0.10 mmol), S-Phos (2.0 mg, 0.005 mmol), and Pd(OAc)2 (0.6 mg, 0.002 mmol) in THF (0.3 mL) and water (0.05 mL) was heated at 100° C. for 14 hours. The reaction mixture was allowed to cool to room temperature. The mixture was then diluted with EtOAc (5 mL), washed with sodium bicarbonate (1 mL) and brine (1 mL), dried over MgSO4, filtered and concentrated. The resulting residue was purified by reverse phase chromatography (Waters Sunfire Prep C18 OBD, 5-45% acetonitrile in water with 0.1% TFA modifier) to afford the title compound. 1H NMR (500 MHz, DMSO): δ 8.83 (dd, J=4.2, 1.6 Hz, 1 H), 8.29 (s, 1 H), 8.20 (d, J=8.5 Hz, 1 H), 8.12 (d, J=2.9 Hz, 1 H), 7.71 (dd, J=8.4, 4.2 Hz, 1 H), 7.30-7.23 (m, 2 H), 4.61 (dd, J=11.3, 6.7 Hz, 1 H), 4.39 (dd, J=11.3, 7.8 Hz, 1 H), 3.78 (s, 3 H), 2.61 (s, 3 H), 2.36 (s, 3 H), 2.20 (dt, J=8.5, 4.6 Hz, 1 H), 1.79 (s, 1 H), 1.24 (s, 1 H), 1.09-1.04 (m, 1 H); HRMS m/z (M+H) 418.1534 found, 418.1536 required.

Workup

  1. temperatureto cool to room temperature
  2. washwashed with sodium bicarbonate (1 mL) and brine (1 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe resulting residue was purified by reverse phase chromatography (Waters Sunfire Prep C18 OBD, 5-45% acetonitrile in water with 0.1% TFA modifier)

Sources & evidence

ORD record
ord-9e81547215b346eabcd72d942529f347
Source dataset
uspto-grants-2015_03
Patent number
US08975261B2

Reaction notes

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