Sodium Carbonate → HCID 178419853, compound

HRID 1846805Notes

Reaction equation

HRID 1846805 reaction equation
[O:1]1[CH2:6][CH:5]=[C:4](B2OC(C)(C)C(C)(C)O2)[CH2:3][CH2:2]1.Cl[C:17]1[C:18]([O:23][C@H:24]2[CH2:29][CH2:28][C@H:27]([NH:30][C:31]3[S:32][C:33]4[CH:39]=[CH:38][CH:37]=[CH:36][C:34]=4[N:35]=3)[CH2:26][CH2:25]2)=[N:19][CH:20]=[CH:21][N:22]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC>[O:1]1[CH2:6][CH:5]=[C:4]([C:17]2[C:18]([O:23][C@H:24]3[CH2:25][CH2:26][C@H:27]([NH:30][C:31]4[S:32][C:33]5[CH:39]=[CH:38][CH:37]=[CH:36][C:34]=5[N:35]=4)[CH2:28][CH2:29]3)=[N:19][CH:20]=[CH:21][N:22]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 178478365HCID 178478365, compound

Product 1

HCID 178419853HCID 178419853, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.10 g, 0.49 mmol) and N-(trans-4-(3-chloropyrazin-2-yloxy)cyclohexyl)benzo[d]thiazol-2-amine (0.14 g, 0.39 mmol), prepared as in step 1 of example 9a, in 1,2-dimethoxyethane (2 mL) and aqueous sodium carbonate (2 M, 0.58 mL, 1.16 mmol) was placed under nitrogen atmosphere using 3 evacuation/backfill cycles. Tetrakis triphenylphosphine(palladium) (0.022 g, 0.019 mmol) was added and one more evacuation/backfill cycle was executed. The mixture was then heated to 80° C. After 4 h the mixture was cooled to RT and partitioned between ethyl acetate and water. The layers were separated and the aqueous layer was extracted with ethyl acetate twice. The combined extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The resulting oil was purified by silica gel chromatography to give N-(trans-4-(3-(3,6-dihydro-2H-pyran-4-yl)pyrazin-2-yloxy)cyclohexyl)benzo[d]thiazol-2-amine (0.13 g, 0.32 mmol, 83% yield). [M+1] 409.2. IC50 (uM): 0.03702.

Workup

  1. temperatureAfter 4 h the mixture was cooled to RT
  2. custompartitioned between ethyl acetate and water
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with ethyl acetate twice
  5. dry with materialThe combined extracts were dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting oil was purified by silica gel chromatography

Sources & evidence

ORD record
ord-e1a05b964c6b4c74bd1da79aadef8269
Source dataset
uspto-grants-2015_02
Patent number
US08952037B2

Reaction notes

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