Potassium Phosphate, Tribasic → HCID 44125329, compound

HRID 1692023Notes

Reaction equation

HRID 1692023 reaction equation
[N:1]1([C@@H:7]2[CH2:11][CH2:10][N:9]([C:12]3[S:13][C:14]4[CH:20]=[C:19]([OH:21])[CH:18]=[CH:17][C:15]=4[N:16]=3)[CH2:8]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl[C:23]1[N:24]=[N:25][C:26]([O:29][CH3:30])=[CH:27][CH:28]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.[OH-].[Na+].C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:30][O:29][C:26]1[N:25]=[N:24][C:23]([O:21][C:19]2[CH:18]=[CH:17][C:15]3[N:16]=[C:12]([N:9]4[CH2:10][CH2:11][C@@H:7]([N:1]5[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]5)[CH2:8]4)[S:13][C:14]=3[CH:20]=2)=[CH:28][CH:27]=1

Participants

7

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 744033-Chloro-6-methoxypyridazineHCID 44124594HCID 44124594, compound

Product 1

HCID 44125329HCID 44125329, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (R)-2-(3-(piperidin-1-yl)pyrrolidin-1-yl)benzo[d]thiazol-6-ol (Example 47, 40 mg, 0.132 mmol), 3-chloro-6-methoxypyridazine (28.6 mg, 0.198 mmol), palladium(II) acetate (2.96 mg, 0.013 mmol), and potassium phosphate tribasic (84 mg, 0.40 mmol) in toluene (1 mL) was heated at 100° C. over night, cooled, diluted with 1 M NaOH (5 mL) and extracted with CH2Cl2 (2×25 mL). The combined CH2Cl2 layers were dried (MgSO4), filtered, concentrated and chromatographed on silica gel eluting with a gradient of 2-10% (9:1 methanol:ammonium hydroxide) in CH2Cl2 to provide the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 1.43-1.53 (m, 2H), 1.58-1.69 (m, 4H), 1.94-2.09 (m, 1H), 2.25-2.36 (m, 1H), 2.40-2.59 (m, 4H), 2.95-3.07 (m, 1H), 3.42 (t, J=9.2 Hz, 1H), 3.54 (dt, J=10.2, 6.8 Hz, 1H), 3.75 (t, J=8.8 Hz, 1H), 3.81-3.89 (m, 1H), 4.04 (s, 3H), 7.02 (d, J=9.2 Hz, 1H), 7.11 (dd, J=8.5, 2.4 Hz, 1H), 7.13 (d, J=9.5 Hz, 1H), 7.49 (d, J=2.7 Hz, 1H), 7.56 (d, J=8.8 Hz, 1H); MS (DCI/NH3) m/z 412 (M+H)+.

Workup

  1. temperaturecooled
  2. extractionextracted with CH2Cl2 (2×25 mL)
  3. dry with materialThe combined CH2Cl2 layers were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customchromatographed on silica gel eluting with a gradient of 2-10% (9:1 methanol:ammonium hydroxide) in CH2Cl2

Sources & evidence

ORD record
ord-5e5f5ff35d98426889a876556b17a582
Source dataset
uspto-grants-2012_04
Patent number
US08153813B2

Reaction notes

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